Jerome Yesavage

All Publications

• Effectiveness of Prefrontal Transcranial Magnetic Stimulation for Depression in Older US Military Veterans. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Walker, N. C., Philip, N. S., Kozel, F. A., Yesavage, J. A., Madore, M. R. 2023

  Abstract

  While typical aging is associated with decreased cortical volume, major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) likely exacerbates this process. Cerebral atrophy leads to increased coil-to-cortex distance and when using transcranial magnetic stimulation (TMS), potentially reducing effectiveness in older adults.Data from a large-scale quality improvement project was used. Included veterans eligible for TMS and completed TMS treatment. Age was assessed as a predictive factor of depression outcomes after TMS treatment among veterans. Secondary analyses examined the impact of age on 1) MDD response and remission and 2) MDD change within MDD-only verses comorbid MDD and PTSD groups.The entire sample included 471 veterans. Primary analysis revealed age as a negative predictor of depression outcomes (p = 0.019). Secondary analyses found age to be a significant predictor of remission (p = 0.004), but not clinical response. Age was not a predictive factor in depression outcomes between those with MDD-only compared to MDD+PTSD.Increased age predicts greater MDD symptom reduction after TMS. Although age did not predict response rates, it did predict increased rates of remission in veterans. Age did not differentially predict depression outcomes between those with or without PTSD. The sample size was sufficient to discern a difference in efficaciousness, and limitations were those inherent to registry studies in veterans. This data indicates that TMS can be an important treatment option for older individuals.

  View details for DOI 10.1016/j.jagp.2023.10.010

  View details for PubMedID 37973487

• Acute Effects of MDMA on Negative Affective Brain Circuit Function: A Randomized Controlled Mechanistic Trial Hack, L., Zhang, X., Heifets, B., Suppes, T., van Roessel, P., Yesavage, J., Gray, N., Hilton, R., Rodriguez, C., Deisseroth, K., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2023: S88

  View details for Web of Science ID 000993018500209

• Multimodal Exercise and Cognitive Training Program Improves Cognitive Function in Amnestic Mild Cognitive Impairment. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Fairchild, J. K., Myers, J., Louras, P., Jo, B., McNerney, M. W., Hallmayer, J., Yesavage, J. 2023

  Abstract

  To investigate the preliminary efficacy of a combined physical exercise + cognitive training intervention for older adults with amnestic mild cognitive impairment (aMCI).Randomized clinical trial.Veteran Affairs Hospital, Palo Alto, CA.Sample included 72 community-dwelling volunteers (mean age 72.4 ± 9.5) diagnosed with aMCI.Participants were randomized to either a combined aerobic and resistance exercise + cognitive training (CARE+CT) or stretching exercise + CT (SE+CT).Primary outcomes included intervention specific assessments of word list and name-face recall. Secondary cognitive outcomes included standardized composite scores that reflect cognitive domains (e.g., learning and memory, executive function, processing speed, visuospatial ability, language). Secondary physiological outcomes included VO2 max and functional capacity (e.g., distance walked 6-minute walk test). APOE and BDNF were determined from whole blood samples.Controlling for age and employment status, linear mixed effects models revealed that all participants experienced significant improvement in the delayed recall of word list, learning and memory and executive function. Only the CARE+CT condition had significant improvement in processing speed and functional capacity. APOE4 status impacted cognitive benefits of those in the SE+CT condition.Results provide preliminary support for combined exercise and cognitive training interventions for older adults with aMCI. Further research is needed to understand the mechanisms involved as well as the impact of these interventions in diverse samples.ClinicalTrials.gov Identifier: NCT01962038.

  View details for DOI 10.1016/j.jagp.2023.12.002

  View details for PubMedID 38220592

• Ketamine's acute effects on negative brain states are mediated through distinct altered states of consciousness in humans. Nature communications Hack, L. M., Zhang, X., Heifets, B. D., Suppes, T., van Roessel, P. J., Yesavage, J. A., Gray, N. J., Hilton, R., Bertrand, C., Rodriguez, C. I., Deisseroth, K., Knutson, B., Williams, L. M. 2023; 14 (1): 6631

  Abstract

  Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain's affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo, 0.05 mg/kg ketamine, and 0.5 mg/kg ketamine in nonclinical adult participants (NCT03475277). Licensed clinicians monitored infusions for safety. Linear mixed effects models, analysis of variance, t-tests, and mediation models were used for statistical analyses. Our design enabled us to test our pre-specified primary and secondary endpoints, which were met: effects of ketamine across dose conditions on (1) emotional task-evoked brain activity, and (2) sub-components of dissociation and other ASCs. With this design, we also could disentangle which ketamine-induced affective brain states are dependent upon specific aspects of ASCs. Differently valenced ketamine-induced ASCs mediated opposing effects on right anterior insula activity. Participants experiencing relatively higher depersonalization induced by 0.5 mg/kg of ketamine showed relief from negative brain states (reduced task-evoked right anterior insula activity, 0.39 SD). In contrast, participants experiencing dissociative amnesia showed an exacerbation of insula activity (0.32 SD). These results in nonclinical participants may shed light on the mechanisms by which specific dissociative states predict response to ketamine in depressed individuals.

  View details for DOI 10.1038/s41467-023-42141-5

  View details for PubMedID 37857620

  View details for PubMedCentralID 5126726

• Personalized repetitive transcranial magnetic stimulation (prtms®) for post-traumatic stress disorder (ptsd) in military combat veterans. Heliyon Makale, M. T., Abbasi, S., Nybo, C., Keifer, J., Christman, L., Fairchild, J. K., Yesavage, J., Blum, K., Gold, M. S., Baron, D., Cadet, J. L., Elman, I., Dennen, C. A., Murphy, K. T. 2023; 9 (8): e18943

  Abstract

  Emerging data suggest that post-traumatic stress disorder (PTSD) arises from disrupted brain default mode network (DMN) activity manifested by dysregulated encephalogram (EEG) alpha oscillations. Hence, we pursued the treatment of combat veterans with PTSD (n = 185) using an expanded form of repetitive transcranial magnetic stimulation (rTMS) termed personalized-rTMS (PrTMS). In this treatment methodology spectral EEG based guidance is used to iteratively optimize symptom resolution via (1) stimulation of multiple motor sensory and frontal cortical sites at reduced power, and (2) adjustments of cortical treatment loci and stimulus frequency during treatment progression based on a proprietary frequency algorithm (PeakLogic, Inc. San Diego) identifying stimulation frequency in the DMN elements of the alpha oscillatory band. Following 4 - 6 weeks of PrTMS® therapy in addition to routine PTSD therapy, veterans exhibited significant clinical improvement accompanied by increased cortical alpha center frequency and alpha oscillatory synchronization. Full resolution of PTSD symptoms was attained in over 50% of patients. These data support DMN involvement in PTSD pathophysiology and suggest a role in therapeutic outcomes. Prospective, sham controlled PrTMS® trials may be warranted to validate our clinical findings and to examine the contribution of DMN targeting for novel preventive, diagnostic, and therapeutic strategies tailored to the unique needs of individual patients with both combat and non-combat PTSD.

  View details for DOI 10.1016/j.heliyon.2023.e18943

  View details for PubMedID 37609394

  View details for PubMedCentralID PMC10440537

• 24 h Rest/Activity Rhythms in Older Adults with Memory Impairment: Associations with Cognitive Performance and Depressive Symptomatology. Advanced biology Antonsdottir, I. M., Low, D. V., Chen, D., Rabinowitz, J. A., Yue, Y., Urbanek, J., Wu, M. N., Zeitzer, J. M., Rosenberg, P. B., Friedman, L. F., Sheikh, J. I., Yesavage, J. A., Zipunnikov, V., Spira, A. P. 2023: e2300138

  Abstract

  Little is known about links of circadian rhythm alterations with neuropsychiatric symptoms and cognition in memory impaired older adults. Associations of actigraphic rest/activity rhythms (RAR) with depressive symptoms and cognition are examined using function-on-scalar regression (FOSR). Forty-four older adults with memory impairment (mean: 76.84 ± 8.15 years; 40.9% female) completed 6.37 ± 0.93 days of actigraphy, the Beck depression inventory-II (BDI-II), mini-mental state examination (MMSE) and consortium to establish a registry for Alzheimer's disease [CERAD] delayed word recall. FOSR models with BDI-II, MMSE, or CERAD as individual predictors adjusted for demographics (Models A1-A3) and all three predictors and demographics (Model B). In Model B, higher BDI-II scores are associated with greater activity from 12:00-11:50 a.m., 2:10-5:50 p.m., 8:40-9:40 p.m., 11:20-12:00 a.m., higher CERAD scores with greater activity from 9:20-10:00 p.m., and higher MMSE scores with greater activity from 5:50-10:50 a.m. and 12:40-5:00 p.m. Greater depressive symptomatology is associated with greater activity in midafternoon, evening, and overnight into midday; better delayed recall with greater late evening activity; and higher global cognitive performance with greater morning and afternoon activity (Model B). Time-of-day specific RAR alterations may affect mood and cognitive performance in this population.

  View details for DOI 10.1002/adbi.202300138

  View details for PubMedID 37423973

• A Cognitive Biotype of Depression and Symptoms, Behavior Measures, Neural Circuits, and Differential Treatment Outcomes: A Prespecified Secondary Analysis of a Randomized Clinical Trial. JAMA network open Hack, L. M., Tozzi, L., Zenteno, S., Olmsted, A. M., Hilton, R., Jubeir, J., Korgaonkar, M. S., Schatzberg, A. F., Yesavage, J. A., O'Hara, R., Williams, L. M. 2023; 6 (6): e2318411

  Abstract

  Cognitive deficits in depression have been associated with poor functional capacity, frontal neural circuit dysfunction, and worse response to conventional antidepressants. However, it is not known whether these impairments combine together to identify a specific cognitive subgroup (or "biotype") of individuals with major depressive disorder (MDD), and the extent to which these impairments mediate antidepressant outcomes.To undertake a systematic test of the validity of a proposed cognitive biotype of MDD across neural circuit, symptom, social occupational function, and treatment outcome modalities.This secondary analysis of a randomized clinical trial implemented data-driven clustering in findings from the International Study to Predict Optimized Treatment in Depression, a pragmatic biomarker trial in which patients with MDD were randomized in a 1:1:1 ratio to antidepressant treatment with escitalopram, sertraline, or venlafaxine extended-release and assessed at baseline and 8 weeks on multimodal outcomes between December 1, 2008, and September 30, 2013. Eligible patients were medication-free outpatients with nonpsychotic MDD in at least the moderate range, and were recruited from 17 clinical and academic practices; a subset of these patients underwent functional magnetic resonance imaging. This prespecified secondary analysis was performed between June 10, 2022, and April 21, 2023.Pretreatment and posttreatment behavioral measures of cognitive performance across 9 domains, depression symptoms assessed using 2 standard depression scales, and psychosocial function assessed using the Social and Occupational Functioning Assessment Scale and World Health Organization Quality of Life scale were analyzed. Neural circuit function engaged during a cognitive control task was measured using functional magnetic resonance imaging.A total of 1008 patients (571 [56.6%] female; mean [SD] age, 37.8 [12.6] years) participated in the overall trial and 96 patients participated in the imaging substudy (45 [46.7%] female; mean [SD] age, 34.5 [13.5] years). Cluster analysis identified what may be referred to as a cognitive biotype of 27% of depressed patients with prominent behavioral impairment in executive function and response inhibition domains of cognitive control. This biotype was characterized by a specific profile of pretreatment depressive symptoms, worse psychosocial functioning (d = -0.25; 95% CI, -0.39 to -0.11; P < .001), and reduced activation of the cognitive control circuit (right dorsolateral prefrontal cortex: d = -0.78; 95% CI, -1.28 to -0.27; P = .003). Remission was comparatively lower in the cognitive biotype positive subgroup (73 of 188 [38.8%] vs 250 of 524 [47.7%]; P = .04) and cognitive impairments persisted regardless of symptom change (executive function: ηp2 = 0.241; P < .001; response inhibition: ηp2 = 0.750; P < .001). The extent of symptom and functional change was specifically mediated by change in cognition but not the reverse.Our findings suggest the presence of a cognitive biotype of depression with distinct neural correlates, and a functional clinical profile that responds poorly to standard antidepressants and instead may benefit from therapies specifically targeting cognitive dysfunction.ClinicalTrials.gov Identifier: NCT00693849.

  View details for DOI 10.1001/jamanetworkopen.2023.18411

  View details for PubMedID 37318808

• Improvements in Immediate and Delayed Memory With Insomnia Therapy and Their Associations With SWA in Older Adults Ahmadi, M., Krause, A. J., O'Hora, K. P., Hernandez, B., Lazzeroni, L., Zeitzer, J. M., Friedman, L. F., Posner, D., Kushida, C. A., Yesavage, J. A., Saletin, J., Goldstein-Piekarski, A. ELSEVIER SCIENCE INC. 2023: S301

  View details for Web of Science ID 000993018500730

• ADULTS WITH AND WITHOUT MILD COGNITIVE IMPAIRMENT SHOW SIMILAR TREATMENT ADHERENCE AND SLEEP IMPROVEMENT AFTER INSOMNIA THERAPY Morehouse, A., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2023

  View details for Web of Science ID 001008232900380

• A Cognitive Biotype of Depression Linking Symptoms, Behavior Measures, Neural Circuits, and Treatment Outcomes Hack, L., Tozzi, L., Zenteno, S., Olmsted, A., Hilton, R., Yesavage, J., Schatzberg, A., O'Hara, R., Williams, L. ELSEVIER SCIENCE INC. 2023: S72-S73

  View details for Web of Science ID 000993018500174

• Ketamine's Acute Effects on Negative Brain States are Mediated Through Distinct Altered States in Humans Zhang, X., Hack, L., Heifets, B., Suppes, T., Van Roessel, P., Yesavage, J., Gray, N., Hilton, R., Rodriguez, C., Deisseroth, K., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2023: S312

  View details for Web of Science ID 000993018500757

• Acute Effects of MDMA on Intrinsic Functional Connectomes Associated With Altered States of Consciousness and Defensiveness Zhang, X., Hack, L., Heifets, B., Suppes, T., van Roessel, P., Yesavage, J., Gray, N., Hilton, R., Rodriguez, C., Deisseroth, K., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2023: S87-S88

  View details for Web of Science ID 000993018500208

• Impact of PTSD and Obstructive Sleep Apnea on Cognition in Older Adult Veterans. Journal of geriatric psychiatry and neurology Noland, M. D., Paolillo, E. W., Noda, A., Lazzeroni, L. C., Holty, J. C., Kuschner, W. G., Yesavage, J., Kinoshita, L. M. 2023: 8919887221149132

  Abstract

  Background: Posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) are highly prevalent and comorbid among older adult male veterans. Both PTSD and OSA are independently associated with cognitive deficits in older adults, but little research regarding the impact of comorbid PTSD and OSA among older adults exists. Purpose: The current study aimed to examine the independent and interactive effects of PTSD and OSA on cognitive functioning in older adult veterans. Study Sample: Older adult male veterans with (n= 106) and without PTSD (n= 69), ranging in age from 55 to 89 (M= 63.35). Data Collection: Participants underwent polysomnography evaluation to assess severity of OSA symptoms and comprehensive neuropsychological evaluation to assess cognitive functioning in 3 domains: attention and processing speed, learning and memory, and executive functioning. Results: Multiple regression analyses showed that the interaction between PTSD and OSA did not predict cognitive performance. However, PTSD significantly predicted poorer attention and processing speed, and increased OSA severity predicted poorer learning and memory. Conclusions: While PTSD and OSA did not have a synergistic detrimental impact on cognition, each independently predicted poorer cognitive functioning within certain domains, suggesting that older adults with these comorbid conditions may experience a wider array of cognitive difficulties.

  View details for DOI 10.1177/08919887221149132

  View details for PubMedID 36592096

• Cognitive Improvement Following Physical Exercise and Cognitive Training Intervention for Older Adults with MCI. The journals of gerontology. Series A, Biological sciences and medical sciences Campbell, E. B., Delgadillo, M., Lazzeroni, L. C., Louras, P. N., Myers, J., Yesavage, J., Fairchild, J. K. 2022

  Abstract

  BACKGROUND: The diagnosis of mild cognitive impairment (MCI) presents a critical period for intervention. Although exercise and cognitive training (CT) interventions have reported independent success for improving cognition, some meta-analyses have suggested combined interventions provide maximal benefits. Much previous research has studied land-based as opposed to water-based exercise, which places potential barriers on older adults. The purpose of the current study was to examine the impact of combined exercise (water- or land-based) and CT treatment on cognition for older adults with MCI.METHODS: Participants were 67 adults ages 54 to 86 years classified with MCI who engaged in six months of land or in aquatic with subsequent CT over four weeks. Primary outcome variables were performance measures of several cognitive domains across three time points (baseline, following exercise intervention, and following CT intervention). Linear mixed effects modeling examined exercise group differences across time periods in an intention-to-treat analysis.RESULTS: Both aquatic- and land-based exercise with CT interventions resulted significant in improvement in learning and memory outcomes, though improvement in executive functioning, processing speed, language, and visuospatial abilities was limited to water-based and CT treatment group. Differences in linear growth patterns between groups were non-significant.CONCLUSIONS: Results suggest that for older adults with MCI to obtain global cognitive benefits (i.e., Learning and Memory, Executive Functioning, Processing Speed, Language, and Visuospatial abilities) using combined exercise and CT interventions, they must be able to fully engage in exercise, and aquatic-based activities should be further considered.

  View details for DOI 10.1093/gerona/glac189

  View details for PubMedID 36099058

• The Benton Visual Form Discrimination Test as a Predictor of Neurocognitive Disorder in Older Veterans. Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists Maruyama, B. A., Alipio Jocson, V. Z., Gretler, J., Doudell, K., Lazzeroni, L. C., Hernandez, B., Noda, A., Yesavage, J. A., Kinoshita, L. M. 2022

  Abstract

  OBJECTIVE: The Benton Visual Form Discrimination Test (VFDT) is a commonly used measure of visual discrimination and visual recognition memory and has shown promise in distinguishing between different levels of cognitive impairment. We assess the predictive diagnostic utility of the VFDT in a sample of older Veterans with cognitive concerns.METHOD: Subjects included a total of 172 mostly male Veterans over the age of 64 (mean=76.0; SD=7.6) recruited from a VA clinic specializing in neuropsychological assessment of older Veterans. The clinical sample included 56 subjects diagnosed with Major Neurocognitive Disorder, 74 diagnosed with Mild Neurocognitive Disorder, and 42 with No Neurocognitive Impairment. Impairment categories were modeled in separate multinomial logistic regressions with two versions of the VFDT as predictors: the Visual Form Discrimination Test-Recognition Subtest (VFDT-Rec) test (visual recognition memory) and the Visual Form Discrimination Test-Matching Subtest VFDT-Mat test (visual form discrimination). Years of education were included as a covariate.RESULTS: After adjusting for education, higher VFDT-Rec total scores were associated with lower odds of being categorized with a greater degree of cognitive/functional impairment (OR 0.66-0.83, p<.001). VFDT-Mat scores showed a similar pattern, but only reached statistical significance for the Major versus No Neurocognitive Impairment (OR=0.77, p=.0010) and Major versus Mild comparisons (OR=0.89, p=.0233).CONCLUSIONS: The VFDT may enhance the confidence of differential diagnosis of dementia in older adult Veterans. Formal education-adjusted norms need to be established for clinical use.

  View details for DOI 10.1093/arclin/acac067

  View details for PubMedID 35965251

• An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-epsilon 4 in female patients with Alzheimer's disease NATURE AGING Jiang, Y., Zhou, X., Wong, H., Ouyang, L., Ip, F. F., Chau, V. N., Lau, S., Wu, W., Wong, D. K., Seo, H., Fu, W., Lai, N. H., Chen, Y., Chen, Y., Tong, E. S., Mok, V. T., Kwok, T. Y., Mok, K. Y., Shoai, M., Lehallier, B., Losada, P., O'Brien, E., Porter, T., Laws, S. M., Hardy, J., Wyss-Coray, T., Masters, C. L., Fu, A. Y., Ip, N. Y., Alzheimer's Dis Neuroimaging Initi 2022; 2 (7): 616-+

  View details for DOI 10.1038/s43587-022-00241-9

  View details for Web of Science ID 000916579000013

• THE IMPACT OF NON-PHARMACOLOGICAL INSOMNIA THERAPY ON MOOD AND SLEEP IN MORNING AND EVENING CHRONOTYPES IN OLDER ADULTS Lopez, M., Krause, A., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2022: A211-A212

  View details for Web of Science ID 000838094800474

• NON-PHARMACOLOGICAL INSOMNIA THERAPY IS ROBUST TO CO-OCCURRING PAIN IN OLDER ADULTS Krause, A., Ahmadi, M., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Saletin, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2022: A197-A198

  View details for Web of Science ID 000838094800441

• THE EFFECT OF DISTINCT COMPONENTS OF CBT-I ON SLOW WAVE POWER AND ENERGY Ahmadi, M., Krause, A., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Saletin, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2022: A197

  View details for Web of Science ID 000838094800440

• THE EFFECTS OF INSOMNIA THERAPY ON DEPRESSION, ANXIETY, AND DAILY FUNCTIONING IN INDIVIDUALS WITH INSOMNIA AND MILD COGNITIVE IMPAIRMENT Morehouse, A., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2022: A275-A276

  View details for Web of Science ID 000838094800623

• Non-Pharmacological Insomnia Therapy is Robust to Co-Occurring Pain in Older Adults Krause, A., Ahmadi, M., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Saletin, J., Goldstein-Piekarski, A. ELSEVIER SCIENCE INC. 2022: S370

  View details for Web of Science ID 000789022201277

• The Effect of Distinct Components of CBT-I on Slow Wave Power and Energy Ahmadi, M., Krause, A. J., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J. A., Saletin, J., Goldstein-Piekarski, A. ELSEVIER SCIENCE INC. 2022: S369-S370

  View details for Web of Science ID 000789022201276

• Repetitive Transcranial Magnetic Stimulation Improves Brain-Derived Neurotrophic Factor and Cholinergic Signaling in the 3xTgAD Mouse Model of Alzheimer's Disease. Journal of Alzheimer's disease : JAD McNerney, M. W., Heath, A., Narayanan, S., Yesavage, J. 1800

  Abstract

  BACKGROUND: Alzheimer's disease (AD) is a debilitating disorder involving the loss of plasticity and cholinergic neurons in the cortex. Pharmaceutical treatments are limited in their efficacy, but brain stimulation is emerging as a treatment for diseases of cognition. More research is needed to determine the biochemical mechanisms and treatment efficacy of this technique.OBJECTIVE: We aimed to determine if forebrain repetitive transcranial magnetic stimulation can improve cortical BDNF gene expression and cholinergic signaling in the 3xTgAD mouse model of AD.METHODS: Both B6 wild type mice and 3xTgAD mice aged 12 months were given daily treatment sessions for 14 days or twice weekly for 6 weeks. Following treatment, brain tissue was extracted for immunological stains for plaque load, as well as biochemical analysis for BDNF gene expression and cholinergic signaling via acetylcholinesterase and choline acetyltransferase ELISA assays.RESULTS: For the 3xTgAD mice, both 14 days and 6 weeks treatment regimens resulted in an increase in BDNF gene expression relative to sham treatment, with a larger increase in the 6-week group. Acetylcholinesterase activity also increased for both treatments in 3xTgAD mice. The B6 mice only had an increase in BDNF gene expression for the 6-week group.CONCLUSION: Brain stimulation is a possible non-invasive and nonpharmaceutical treatment option for AD as it improves both plasticity markers and cholinergic signaling in an AD mouse model.

  View details for DOI 10.3233/JAD-215361

  View details for PubMedID 35068462

• Targeting the Salience Network: A Mini-Review on a Novel Neuromodulation Approach for Treating Alcohol Use Disorder. Frontiers in psychiatry Padula, C. B., Tenekedjieva, L., McCalley, D. M., Al-Dasouqi, H., Hanlon, C. A., Williams, L. M., Kozel, F. A., Knutson, B., Durazzo, T. C., Yesavage, J. A., Madore, M. R. 2022; 13: 893833

  Abstract

  Alcohol use disorder (AUD) continues to be challenging to treat despite the best available interventions, with two-thirds of individuals going on to relapse by 1 year after treatment. Recent advances in the brain-based conceptual framework of addiction have allowed the field to pivot into a neuromodulation approach to intervention for these devastative disorders. Small trials of repetitive transcranial magnetic stimulation (rTMS) have used protocols developed for other psychiatric conditions and applied them to those with addiction with modest efficacy. Recent evidence suggests that a TMS approach focused on modulating the salience network (SN), a circuit at the crossroads of large-scale networks associated with AUD, may be a fruitful therapeutic strategy. The anterior insula or dorsal anterior cingulate cortex may be particularly effective stimulation sites given emerging evidence of their roles in processes associated with relapse.

  View details for DOI 10.3389/fpsyt.2022.893833

  View details for PubMedID 35656355

• Repetitive Transcranial Magnetic Stimulation as a Treatment for Veterans with Cognitive Impairment and Multiple Comorbidities. Journal of Alzheimer's disease : JAD Cheng, J., Fairchild, J. K., McNerney, M. W., Noda, A., Ashford, J. W., Suppes, P., Chao, S. Z., Taylor, J., Rosen, A., Durazzo, T., Lazzeroni, L. C., Yesavage, J. 1800

  Abstract

  BACKGROUND: Despite decades of research efforts, current treatments for Alzheimer's disease (AD) are of limited effectiveness and do not halt the progression of the disease and associated cognitive decline. Studies have shown that repetitive transcranial magnetic stimulation (rTMS) may improve cognition.OBJECTIVE: We conducted a pilot study to investigate the effect of rTMS on cognitive function in Veterans with numerous medical comorbidities.METHODS: Participants underwent 20 sessions, over the course of approximately 4 weeks, of 10 Hz rTMS at the left dorsolateral prefrontal cortex with intensity of 120% resting motor threshold. Outcome measures including memory, language, verbal fluency, and executive functions were acquired at baseline, end of treatment, and 4 months after the last rTMS session. Twenty-six Veterans completed the study (13 in the active rTMS group, 13 in the sham rTMS group).RESULTS: The study protocol was well-tolerated. Active, compared to sham, rTMS showed improved auditory-verbal memory at the end of treatment and at 4-month follow-up. However, the active rTMS group demonstrated a trend in decreased semantic verbal fluency at the end of treatment and at 4-month follow up.CONCLUSION: These preliminary results show rTMS is safe in general in this elderly Veteran population with multiple co-morbidities. Patients in the sham group showed an expected, slight decline in the California Verbal Learning Test scores over the course of the study, whereas the active treatment group showed a slight improvement at the 4-month post-treatment follow up. These effects need to be confirmed by studies of larger sample sizes.

  View details for DOI 10.3233/JAD-210349

  View details for PubMedID 34958013

• Ruminative reflection is associated with anticorrelations between the orbitofrontal cortex and the default mode network in depression: implications for repetitive transcranial magnetic stimulation. Brain imaging and behavior Ehrlich, T. J., Bhat, J., Horwege, A. M., Mathalon, D. H., Glover, G. H., Roach, B. J., Badran, B. W., Forman, S. D., George, M. S., Scott, J. C., Thase, M. E., Yesavage, J. A., Yurgelun-Todd, D. A., Rosen, A. C. 2021

  Abstract

  Patients with depression who ruminate repeatedly focus on depressive thoughts; however, there are two cognitive subtypes of rumination, reflection and brooding, each associated with different prognoses. Reflection involves problem-solving and is associated with positive outcomes, whereas brooding involves passive, negative, comparison with other people and is associated with poor outcomes. Rumination has also been related to atypical functional hyperconnectivity between the default mode network and subgenual prefrontal cortex. Repetitive pulse transcranial magnetic stimulation of the prefrontal cortex has been shown to alter functional connectivity, suggesting that the abnormal connectivity associated with rumination could potentially be altered. This study examined potential repetitive pulse transcranial magnetic stimulation prefrontal cortical targets that could modulate one or both of these rumination subtypes. Forty-three patients who took part in a trial of repetitive pulse transcranial magnetic stimulation completed the Rumination Response Scale questionnaire and resting-state functional magnetic resonance imaging. Seed to voxel functional connectivity analyses identified an anticorrelation between the left lateral orbitofrontal cortex (-44, 26, -8; k=172) with the default mode network-subgenual region in relation to higher levels of reflection. Parallel analyses were not significant for brooding or the RRS total score. These findings extend previous studies of rumination and identify a potential mechanistic model for symptom-based neuromodulation of rumination.

  View details for DOI 10.1007/s11682-021-00596-4

  View details for PubMedID 34860349

• Survivors of SARS-CoV-2 Infection Show Neuropsychiatric Sequelae Measured by Surveys, Neurocognitive Testing, and Magnetic Resonance Imaging: Preliminary Results Hack, L., Brawer, J., Zhang, X., Wintermark, M., Jiang, B., Stetz, P., Yesavage, J., Grant, P., Bonilla, H., Subramanian, A., Williams, L. SPRINGERNATURE. 2021: 205-206

  View details for Web of Science ID 000725511400390

• Accelerated functional brain aging in pre-clinical familial Alzheimer's disease NATURE COMMUNICATIONS Gonneaud, J., Baria, A. T., Binette, A., Gordon, B. A., Chhatwal, J. P., Cruchaga, C., Jucker, M., Levin, J., Salloway, S., Farlow, M., Gauthier, S., Benzinger, T. S., Morris, J. C., Bateman, R. J., Breitner, J. S., Poirier, J., Vachon-Presseau, E., Villeneuve, S., Alzheimer's Dis Neuroimaging Initi, Dominantly Inherited Alzheimer Net, Presymptomatic Evaluation Expt No 2021; 12 (1): 5346

  Abstract

  Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer's disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of AD, as well as beta-amyloid (Aβ) pathology, can accelerate brain aging. Using data from 1340 cognitively unimpaired participants between 18-94 years of age from multiple sites, we showed that topological properties of graphs constructed from rs-fMRI can predict chronological age across the lifespan. Application of our predictive model to the context of pre-clinical AD revealed that the pre-symptomatic phase of autosomal dominant AD includes acceleration of functional brain aging. This association was stronger in individuals having significant Aβ pathology.

  View details for DOI 10.1038/s41467-021-25492-9

  View details for Web of Science ID 000695204000015

  View details for PubMedID 34504080

  View details for PubMedCentralID PMC8429427

• Brainstem damage is associated with poorer sleep quality and increased pain in gulf war illness veterans. Life sciences Zhang, Y., Vakhtin, A. A., Dietch, J., Jennings, J. S., Yesavage, J. A., Clark, J. D., Bayley, P. J., Ashford, J. W., Furst, A. J. 2021: 119724

  Abstract

  AIMS: Gulf War Illness (GWI) is manifested as multiple chronic symptoms, including chronic pain, chronic fatigue, sleep problems, neuropsychiatric disorders, respiratory, gastrointestinal, and skin problems. No single target tissue or unifying pathogenic process has been identified that accounts for this variety of symptoms. The brainstem has been suspected to contribute to this multiple symptomatology. The aim of this study was to assess the role of the brainstem in chronic sleep problems and pain in GWI veterans.MATERIALS AND METHODS: We enrolled 90 veterans (Age = 50 ± 5, 87% Male) who were deployed to the 1990-91 Gulf War and presented with GWI symptoms. Sleep quality was evaluated using the global Pittsburgh Sleep Quality Index. Pain intensities were obtained with the Brief Pain Inventory sum score. Volumes in cortical, subcortical, brainstem, and brainstem subregions and diffusion tensor metrics in 10 bilateral brainstem tracts were tested for correlations with symptom measures.KEY FINDINGS: Poorer sleep quality was significantly correlated with atrophy of the whole brainstem and brainstem subregions (including midbrain, pons, medulla). Poorer sleep quality also significantly correlated with lower fractional anisotropy in the nigrostriatal tract, medial forebrain tract, and the dorsal longitudinal fasciculus. There was a significant correlation between increased pain intensity and decreased fractional anisotropy in the dorsal longitudinal fasciculus. These correlations were not altered after controlling for age, sex, total intracranial volumes, or additional factors, e.g., depression and neurological conditions.SIGNIFICANCE: These findings suggest that the brainstem plays an important role in the aberrant neuromodulation of sleep and pain symptoms in GWI.

  View details for DOI 10.1016/j.lfs.2021.119724

  View details for PubMedID 34144059

• INTERVENTION AMONG PAP USERS NEWLY DIAGNOSED WITH OSA IMPROVES LONG-TERM ADHERENCE IN VETERANS WITH SLEEP APNEA AND PTSD Gretler, J., Noland, M., Jocson, V., Chen, M., Dominguez, C., Hernandez, B., Noda, A., Holty, J., Kuschner, W., Yesavage, J., Kinoshita, L. OXFORD UNIV PRESS INC. 2021: A175

  View details for Web of Science ID 000698984300442

• EFFICACY OF CBT-I AND ITS COMPONENTS ON HEALTH-RELATED QUALITY OF LIFE OUTCOMES IN OLDER ADULTS Showen, K., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2021: A143-A144

  View details for Web of Science ID 000698984300359

• RELATIVE EFFECTIVENESS OF COGNITIVE BEHAVIORAL THERAPY AND ITS COMPONENTS IN IMPROVING INSOMNIA SYMPTOMS IN OLDER ADULTS O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2021: A144

  View details for Web of Science ID 000698984300360

• Posttraumatic Stress Disorder-Associated Cognitive Deficits on the Repeatable Battery for the Assessment of Neuropsychological Status in a Veteran Population. Federal practitioner : for the health care professionals of the VA, DoD, and PHS Hantke, N. n., Adamson, M. M., Noda, A. n., Lazzeroni, L. C., Beaudreau, S. A., Yutsis, M. n., Fairchild, J. K., Kinoshita, L. M., Kong, J. n., Sheng, T. n., Waltzman, D. n., Ashford, J. W., Yesavage, J. A. 2021; 38 (1): 28–34

  Abstract

  Posttraumatic stress disorder (PTSD) is a frequent problem of veterans receiving care and is often associated with cognitive deficits. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a well-validated cognitive screening measure often used in the US Department of Veterans Affairs (VA), particularly in neurorehabilitation settings. However, the influence of PTSD on RBANS performance is unclear, particularly within a heterogeneous VA outpatient population in which PTSD and traumatic brain injury (TBI) may not be the primary focus of care.Participants included 153 veterans with complex deployment-related health problems, including a diagnosis of PTSD (n = 98) and a history of TBI (n = 92). All veterans completed a targeted cognitive battery that included the Wechsler Test of Adult Reading, the Wechsler Adults Intelligence Scale, measure assessing processing speed, attention, and cognitive flexibility, and RBANS.A diagnosis of PTSD was associated with worse performance on the Story Recall subtest of the RBANS, but not on any other cognitive measures. A diagnosis of mild TBI, or co-occurring PTSD and TBI did not predict cognitive performance on any measures.The RBANS best captured cognitive deficits associated with PTSD compared with a history of mild TBI or co-occurring mild TBI and PTSD. These findings may provide insight into the interpretation and attribution of cognitive deficits in the veteran population.

  View details for DOI 10.12788/fp.0083

  View details for PubMedID 33574646

  View details for PubMedCentralID PMC7870275

• Prefrontal Transcranial Magnetic Stimulation for Depression in US Military Veterans - A Naturalistic Cohort Study in the Veterans Health Administration. Journal of affective disorders Madore, M. R., Kozel, F. A., Williams, L. M., Green, L. C., George, M. S., Holtzheimer, P. E., Yesavage, J. A., Philip, N. S. 2021

  Abstract

  Repetitive transcranial magnetic stimulation (TMS) is an evidence-based treatment for pharmacoresistant major depressive disorder (MDD), however, the evidence in veterans has been mixed. To this end, VA implemented a nationwide TMS program that included evaluating clinical outcomes within a naturalistic design. TMS was hypothesized to be safe and provide clinically meaningful reductions in MDD and posttraumatic stress disorder (PTSD) symptoms.Inclusion criteria were MDD diagnosis and standard clinical TMS eligibility. Of the 770 patients enrolled between October 2017 and March 2020, 68.4% (n=521) met threshold-level PTSD symptom criteria. Treatments generally used standard parameters (e.g., left dorsolateral prefrontal cortex, 120% motor threshold, 10Hz, 3000 pulses/treatment). Adequate dose was operationally defined as 30 sessions. MDD and PTSD symptoms were measured using the 9-item patient health questionnaire (PHQ-9) and PTSD checklist for DSM-5 (PCL-5), respectively.Of the 770 who received at least one session, TMS was associated with clinically meaningful (Cohen's d>1.0) and statistically significant (all p<.001) reductions in MDD and PTSD. Of the 340 veterans who received an adequate dose, MDD response and remission rates were 41.4% and 20%, respectively. In veterans with comorbid PTSD, 65.3% demonstrated clinically meaningful reduction and 46.1% no longer met threshold criteria after TMS. Side effects were consistent with the known safety profile of TMS.Include those inherent to retrospective observational cohort study in Veterans.These multisite, large-scale data supports the effectiveness and safety of TMS for veterans with MDD and PTSD using standard clinical approaches.

  View details for DOI 10.1016/j.jad.2021.10.025

  View details for PubMedID 34687780

• Brain health registry GenePool study: A novel approach to online genetics research. Alzheimer's & dementia (New York, N. Y.) Fockler, J., Kwang, W., Ashford, M. T., Flenniken, D., Hwang, J., Truran, D., Mackin, R. S., Jin, C., O'Hara, R., Hallmayer, J. F., Yesavage, J. A., Weiner, M. W., Nosheny, R. L. 2021; 7 (1): e12118

  Abstract

  Introduction: Remote data collection, including the establishment of online registries, is a novel approach to efficiently identify risk for cognitive decline and Alzheimer's disease (AD) in older adults, with growing evidence for feasibility and validity. Addition of genetic data to online registries has the potential to facilitate identification of older adults at risk and to advance the understanding of genetic contributions to AD.Methods: 573 older adult participants with longitudinal online Brain Health Registry (BHR) data underwent apolipoprotein E (APOE) genotyping using remotely collected saliva samples and a novel, automated Biofluid Collection Management Portal. We evaluated acceptability of genetic sample collection and estimated associations between (1) sociodemographic variables and willingness to participate in genetics research and (2) APOE results and online cognitive and functional assessments. We also assessed acceptance of hypothetical genetics research participation by surveying a larger sample of 25,888 BHR participants.Results: 51% of invited participants enrolled in the BHR genetics study, BHR-GenePool Study (BHR-GPS); 27% of participants had at least one APOE epsilon4 allele. Older participants and those with higher educational attainment were more likely to participate. In the remotely administered Cogstate Brief Battery, APOE epsilon4/epsilon4 homozygotes (HM) had worse online learning scores, and greater decline in processing speed and attention, compared to epsilon3/epsilon4 heterozygotes (HT) and epsilon4 non-carriers (NC).Discussion: APOE genotyping of more than 500 older adults enrolled in BHR supports the feasibility and validity of a novel, remote biofluids collection approach from a large cohort of older adults, with data linkage to longitudinal online cognitive data. This approach can be expanded for efficient collection of genetic data and other information from biofluids in the future.

  View details for DOI 10.1002/trc2.12118

  View details for PubMedID 33614891

• Default Mode Network Connectivity and Brain Derived Trophic Factor in Brain Stimulation of TBI patients Adamson, M., McNerney, M., Siddiqi, S., Swaminath, G., Wu, L., Hernandez, B., Lazzeroni, L., Yesavage, J. ELSEVIER SCIENCE INC. 2020: S158

  View details for Web of Science ID 000535308200379

• FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease NATURE COMMUNICATIONS Yan, T., Liang, J., Gao, J., Wang, L., Fujioka, H., Zhu, X., Wang, X., Weiner, M. W., Schuff, N., Rosen, H. J., Miller, B. L., Perry, D., Aisen, P., Toga, A. W., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Toga, A. W., Crawford, K., Neu, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Aisen, P., Petersen, R., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Jagust, W., Landau, S., Trojanowki, J. Q., Shaw, L. M., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Lee, V., Korecka, M., Figurski, M., Beckett, L., Harvey, D., DeCArli, C., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Green, R. C., Sperling, R. A., Johnson, K. A., Marshall, G. A., Saykin, A. J., Foroud, T. M., Shen, L., Faber, K., Kim, S., Nho, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., Morris, J., Raichle, M., Holtzman, D., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Kuller, L., Mathis, C., Lopez, O. L., Oakley, M., Simpson, D. M., Paul, S., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Davies, P., Mesulam, M., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Snyder, P. J., Montine, T., Donohue, M., Thal, L., Brewer, J., Vanderswag, H., Fleisher, A., Thompson, P., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Koeppe, R. A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Foster, N., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Marson, D., Geldmacher, D., Natelson, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Potkin, S., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Turner, R., Johnson, K., Reynolds, B., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Johnson, S., Asthana, S., Carlsson, C. M., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Smith, A., Leach, C., Raj, B., Fargher, K., Reiman, E. M., Chen, K., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Zamrini, E., Belden, C. M., Sirrel, S. A., Duara, R., Greig-Custo, M. T., Rodriguez, R., Bernick, C., Munic, D., Khachaturian, Z., Buckholtz, N., Hsiao, J., Potter, W., Fillit, H., Hefti, F., Sadowsky, C., Villena, T., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Black, S., Stefanovic, B., Heyn, C., Ott, B. R., Tremont, G., Daniello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Pearlson, G. D., Blank, K., Anderson, K., Bates, V., Capote, H., Rainka, M., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Kittur, S., Borrie, M., Lee, T., Bartha, R., Frank, R., Fox, N., Logovinsky, V., Corrillo, M., Sorensen, G., Alzheimer Dis Neuroimaging 2020; 11 (1): 411

  Abstract

  Alzheimer's disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD.

  View details for DOI 10.1038/s41467-019-13962-0

  View details for Web of Science ID 000511941200001

  View details for PubMedID 31964863

  View details for PubMedCentralID PMC6972869

• Does Nitrous Oxide Help Veterans With Posttraumatic Stress Disorder? A Case Series. The Journal of clinical psychiatry Varias, A. n., van Roessel, P. n., Parsiani, M. n., Filippou-Frye, M. n., Neylan, T. C., Nagele, P. n., Yesavage, J. n., Clark, J. D., Rodriguez, C. I. 2020; 81 (4)

  View details for DOI 10.4088/JCP.20l13393

  View details for PubMedID 32609959

• A Clinical Program to Implement Repetitive Transcranial Magnetic Stimulation for Depression in the Department of Veterans Affairs. Federal practitioner : for the health care professionals of the VA, DoD, and PHS Carrico, W. T., Georgette, G. n., Madore, M. R., Kozel, F. A., George, M. S., Lindley, S. n., Lovett, S. n., Yoon, J. H., Yesavage, J. A. 2020; 37 (6): 276–81

  Abstract

  Repetitive transcranial magnetic stimulation (rTMS) uses a device to create magnetic fields that cause electrical current to flow into targeted neurons in the brain. The most common clinical use of rTMS is for the treatment of major depressive disorder (MDD). The annual suicide rate of veterans has been higher than the national average; treating depression with rTMS would likely decrease suicide risk. MDD in many patients can be chronic and reoccurring with medication and psychotherapy providing inadequate relief.A pilot program was created to supply rTMS devices to 35 different sites in the VA nationwide in order to treat treatment-resistant depression.At time of analysis more than 950 veterans have started the program and 412 have finished. Nationwide, we have seen the depression scores decline, indicating an improvement in well-being. In addition, there is high patient satisfaction. Collecting data on a national level is a powerful way to examine rTMS efficacy and predictors of response which might be lost on a smaller subset of cases.

  View details for PubMedID 32669780

  View details for PubMedCentralID PMC7357884

• A Novel Joint Brain Network Analysis Using Longitudinal Alzheimer's Disease Data SCIENTIFIC REPORTS Kundu, S., Lukemire, J., Wang, Y., Guo, Y., Weiner, M. W., Schuff, N., Rosen, H. J., Miller, B. L., Neylan, T., Hayes, J., Finley, S., Aisen, P., Khachaturian, Z., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Thal, L., Brewer, J., Vanderswag, H., Fleisher, A., Davis, M., Morrison, R., Petersen, R., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Jagust, W., Landau, S., Trojanowki, J. Q., Shaw, L. M., Lee, V., Korecka, M., Figurski, M., Arnold, S. E., Karlawish, J. H., Wolk, D., Toga, A. W., Crawford, K., Neu, S., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Beckett, L., Harvey, D., Fletcher, E., Carmichael, O., Olichney, J., DeCarli, C., Green, R. C., Sperling, R. A., Johnson, K. A., Marshall, G., Frey, M., Lane, B., Rosen, A., Tinklenberg, J., Saykin, A. J., Foroud, T. M., Shen, L., Faber, K., Kim, S., Nho, K., Farlow, M. R., Hake, A., Matthews, B. R., Herring, S., Hunt, C., Morris, J., Raichle, M., Holtzman, D., Cairns, N. J., Householder, E., Taylor-Reinwald, L., Ances, B., Carroll, M., Leon, S., Mintun, M. A., Schneider, S., Oliver, A., Raudin, L., Sorensen, G., Kuller, L., Mathis, C., Lopez, O. L., Oakley, M., Paul, S., Relkin, N., Chaing, G., Davies, P., Fillit, H., Hefti, F., Mesulam, M., Kerwin, D., Mesulam, M., Lipowski, K., Wu, C., Johnson, N., Grafman, J., Potter, W., Snyder, P., Schwartz, A., Montine, T., Peskind, E. R., Fox, N., Thompson, P., Apostolova, L., Tingus, K., Woo, E., Silverman, D. S., Lu, P. H., Bartzokis, G., Koeppe, R. A., Heidebrink, J. L., Lord, J. L., Potkin, S. G., Preda, A., Nguyenv, D., Foster, N., Reiman, E. M., Chen, K., Tariot, P., Reeder, S., Potkin, S., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., Buckholtz, N., Hsiao, J., Albert, M., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Simpson, D. M., Frank, R., Kaye, J., Quinn, J., Lind, B., Carter, R., Dolen, S., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Grossman, H., Mitsis, E., de Toledo-Morrell, L., Shah, R. C., Fleischman, D., Arfanakis, K., Duara, R., Varon, D., Greig, M. T., Roberts, P., Galvin, J. E., Cerbone, B., Michel, C. A., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P., Petrella, J. R., Wong, T. Z., James, O., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M., Brand, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Weiner, M., Martin-Cook, K., DeVous, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Swerdlow, R. H., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, G., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Bernick, C., Munic, D., Finger, E., Pasternak, S., Rachinsky, I., Drost, D., Sadowsky, C., Martinez, W., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Allard, J., Lerner, A., Ogrocki, P., Hudson, L., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Fruehling, J., Harding, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Petrie, E. C., Li, G., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Santulli, R. B., Kitzmiller, T. J., Schwartz, E. S., Sink, K. M., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Mintzer, J., Spicer, K., Bachman, D., Massoglia, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Ponto, L., Shim, H., Smith, K., Smith, A., Fargher, K., Raj, B., Friedl, K., Yesavage, J. A., Taylor, J. L., Furst, A. J., Alzheimers Dis Neuroimaging Initia 2019; 9: 19589

  Abstract

  There is well-documented evidence of brain network differences between individuals with Alzheimer's disease (AD) and healthy controls (HC). To date, imaging studies investigating brain networks in these populations have typically been cross-sectional, and the reproducibility of such findings is somewhat unclear. In a novel study, we use the longitudinal ADNI data on the whole brain to jointly compute the brain network at baseline and one-year using a state of the art approach that pools information across both time points to yield distinct visit-specific networks for the AD and HC cohorts, resulting in more accurate inferences. We perform a multiscale comparison of the AD and HC networks in terms of global network metrics as well as at the more granular level of resting state networks defined under a whole brain parcellation. Our analysis illustrates a decrease in small-worldedness in the AD group at both the time points and also identifies more local network features and hub nodes that are disrupted due to the progression of AD. We also obtain high reproducibility of the HC network across visits. On the other hand, a separate estimation of the networks at each visit using standard graphical approaches reveals fewer meaningful differences and lower reproducibility.

  View details for DOI 10.1038/s41598-019-55818-z

  View details for Web of Science ID 000508872700035

  View details for PubMedID 31863067

  View details for PubMedCentralID PMC6925181

• Sleep-wake disorders in Alzheimer's disease: further genetic analyses in relation to objective sleep measures. International psychogeriatrics Yesavage, J. A., Noda, A., Heath, A., McNerney, M. W., Domingue, B. W., Hernandez, Y., Benson, G., Hallmayer, J., O'Hara, R., Williams, L. M., Goldstein-Piekarski, A. N., Zeitzer, J. M., Fairchild, J. K. 2019: 1–7

  Abstract

  This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer's disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.

  View details for DOI 10.1017/S1041610219001777

  View details for PubMedID 31739820

• Multimodal Hippocampal Subfield Grading For Alzheimer's Disease Classification SCIENTIFIC REPORTS Hett, K., Vinh-Thong Ta, Catheline, G., Tourdias, T., Manjon, J. V., Coupe, P., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Thomas, R. G., Donohue, M., Walter, S., Sather, T., Jiminez, G., Balasubramanian, A. B., Mason, J., Sim, I., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., Decarli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Cairns, N. J., Householder, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Frank, R., Hsiao, J., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Ances, B., Carroll, M., Creech, M. L., Franklin, E., Mintun, M. A., Schneider, S., Oliver, A., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Love, M., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Grossman, H., Mitsis, E., Shah, R. C., deToledo-Morrell, L., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Duara, R., Varon, D., Greig, M. T., Roberts, P., Stern, Y., Honig, L. S., Bell, K. L., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Galvin, J. E., Cerbone, B., Michel, C. A., Pogorelec, D. M., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Womack, K., Mathews, D., Quiceno, M., Doraiswamy, P., Petrella, J. R., Borges-Neto, S., Wong, T. Z., Coleman, E., Levey, A. I., Lah, J. J., Cella, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Arnold, S. E., Karlawish, J. H., Wolk, D., Clark, C. M., Apostolova, L., Tingus, K., Woo, E., Silverman, D. S., Lu, P. H., Bartzokis, G., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., Lopez, O. L., Oakley, M., Simpson, D. M., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., Hunt, C., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M., Brand, C., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, G., Feldman, H., Mudge, B., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Trost, D., Kertesz, A., Bernick, C., Munic, D., Lipowski, K., Weintraub, M., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Preda, A., Nguyen, D., Tariot, P., Burke, A., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Gordineer, L., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Ponto, L., Shim, H., Smith, K., Relkin, N., Chaing, G., Lin, M., Ravdin, L., Smith, A., Raj, B., Fargher, K., Alzheimers Dis Neuroimaging Ini 2019; 9: 13845

  Abstract

  Numerous studies have proposed biomarkers based on magnetic resonance imaging (MRI) to detect and predict the risk of evolution toward Alzheimer's disease (AD). Most of these methods have focused on the hippocampus, which is known to be one of the earliest structures impacted by the disease. To date, patch-based grading approaches provide among the best biomarkers based on the hippocampus. However, this structure is complex and is divided into different subfields, not equally impacted by AD. Former in-vivo imaging studies mainly investigated structural alterations of these subfields using volumetric measurements and microstructural modifications with mean diffusivity measurements. The aim of our work is to improve the current classification performances based on the hippocampus with a new multimodal patch-based framework combining structural and diffusivity MRI. The combination of these two MRI modalities enables the capture of subtle structural and microstructural alterations. Moreover, we propose to study the efficiency of this new framework applied to the hippocampal subfields. To this end, we compare the classification accuracy provided by the different hippocampal subfields using volume, mean diffusivity, and our novel multimodal patch-based grading framework combining structural and diffusion MRI. The experiments conducted in this work show that our new multimodal patch-based method applied to the whole hippocampus provides the most discriminating biomarker for advanced AD detection while our new framework applied into subiculum obtains the best results for AD prediction, improving by two percentage points the accuracy compared to the whole hippocampus.

  View details for DOI 10.1038/s41598-019-49970-9

  View details for Web of Science ID 000487586600036

  View details for PubMedID 31554909

• New Perspective for Non-invasive Brain Stimulation Site Selection in Mild Cognitive Impairment: Based on Meta- and Functional Connectivity Analyses FRONTIERS IN AGING NEUROSCIENCE Liu, J., Zhang, B., Wilson, G., Kong, J., Alzheimer's Dis Neuroimaging Init 2019; 11: 228

  Abstract

  Non-invasive brain stimulation (NIBS) has been widely used to treat mild cognitive impairment (MCI). However, there exists no consensus on the best stimulation sites.To explore potential stimulation locations for NIBS treatment in patients with MCI, combining meta- and resting state functional connectivity (rsFC) analyses.The meta-analysis was conducted to identify brain regions associated with MCI. Regions of interest (ROIs) were extracted based on this meta-analysis. The rsFC analysis was applied to 45 MCI patients to determine brain surface regions that are functionally connected with the above ROIs.We found that the dorsolateral prefrontal cortex (DLPFC) and inferior frontal gyrus (IFG) were the overlapping brain regions between our results and those of previous studies. In addition, we recommend that the temporoparietal junction (including the angular gyrus), which was found in both the meta- and rsFC analysis, should be considered in NIBS treatment of MCI. Furthermore, the bilateral orbital prefrontal gyrus, inferior temporal gyrus, medial superior frontal gyrus, and right inferior occipital gyrus may be potential brain stimulation sites for NIBS treatment of MCI.Our results provide several potential sites for NIBS, such as the DLFPC and IFG, and may shed light on the locations of NIBS sites in the treatment of patients with MCI.

  View details for DOI 10.3389/fnagi.2019.00228

  View details for Web of Science ID 000482809900001

  View details for PubMedID 31551754

  View details for PubMedCentralID PMC6736566

• Recommendations for the Nonpharmacological Treatment of Apathy in Brain Disorders. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Manera, V., Abrahams, S., Aguera-Ortiz, L., Bremond, F., David, R., Fairchild, K., Gros, A., Hanon, C., Husain, M., Konig, A., Lockwood, P. L., Pino, M., Radakovic, R., Robert, G., Slachevsky, A., Stella, F., Tribouillard, A., Trimarchi, P. D., Verhey, F., Yesavage, J., Zeghari, R., Robert, P. 2019

  Abstract

  Apathy is a common neuropsychiatric syndrome observed across many neurocognitive and psychiatric disorders. Although there are currently no definitive standard therapies for the treatment of apathy, nonpharmacological treatment (NPT) is often considered to be at the forefront of clinical management. However, guidelines on how to select, prescribe, and administer NPT in clinical practice are lacking. Furthermore, although new Information and Communication Technologies (ICT) are beginning to be employed in NPT, their role is still unclear. The objective of the present work is to provide recommendations for the use of NPT for apathy, and to discuss the role of ICT in this domain, based on opinions gathered from experts in the field. The expert panel included 20 researchers and healthcare professionals working on brain disorders and apathy. Following a standard Delphi methodology, experts answered questions via several rounds of web-surveys, and then discussed the results in a plenary meeting. The experts suggested that NPT are useful to consider as therapy for people presenting with different neurocognitive and psychiatric diseases at all stages, with evidence of apathy across domains. The presence of a therapist and/or a caregiver is important in delivering NPT effectively, but parts of the treatment may be performed by the patient alone. NPT can be delivered both in clinical settings and at home. However, while remote treatment delivery may be cost and time-effective, it should be considered with caution, and tailored based on the patient's cognitive and physical profile and living conditions.

  View details for DOI 10.1016/j.jagp.2019.07.014

  View details for PubMedID 31495772

• Non-coding variability at the APOE locus contributes to the Alzheimer's risk NATURE COMMUNICATIONS Zhou, X., Chen, Y., Mok, K. Y., Kwok, T. Y., Mok, V. T., Guo, Q., Ip, F. C., Chen, Y., Mullapudi, N., Giusti-Rodriguez, P., Sullivan, P. F., Hardy, J., Fu, A. Y., Li, Y., Ip, N. Y., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowski, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M. M., Potter, W., Snyder, P., Schwartz, A., Montine, T., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Harvey, D., Bernstein, M., Thompson, P., Schuff, N., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Cairns, N. J., Householder, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S. G., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Buckholtz, N., Albert, M., Frank, R., Hsiao, J., Kaye, J., Quinn, J., Lind, B., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Ances, B., Carroll, M., Leon, S., Mintun, M. A., Schneider, S., Oliver, A., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Grossman, H., Mitsis, E., De Toledo-Morrell, L., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Roberts, P., Onyike, C., D'Agostino, D., Kielb, S., Galvin, J. E., Cerbone, B., Michel, C. A., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P., Petrella, J. R., Wong, T. Z., Arnold, S. E., Karlawish, J. H., Wolk, D., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M., Brand, C., Mulnard, R. A., Thai, G., McAdams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Weiner, M., Martin-Cook, K., DeVous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Swerdlow, R. H., Apostolova, L., Tingus, K., Woo, E., Silverman, D. S., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., Farlow, M. R., Hake, A., Matthews, B. R., Herring, S., Hunt, C., Van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Chertkow, H., Bergman, H., Hosein, C., Hsiung, G., Feldman, H., Mudge, B., Assaly, M., Bernick, C., Munic, D., Kertesz, A., Rogers, J., Trost, D., Kerwin, D., Lipowski, K., Wu, C., Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Frey, M., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Allard, J., Lerner, A., Ogrocki, P., Hudson, L., Fletcher, E., Carmichael, O., Olichney, J., DeCarli, C., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Preda, A., Nguyen, D., Tariot, P., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Santulli, R. B., Kitzmiller, T. J., Schwartz, E. S., Sink, K. M., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rachinsky, I., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Ponto, L., Shim, H., Smith, K., Relkin, N., Chaing, G., Raudin, L., Smith, A., Fargher, K., Raj, B., Neylan, T., Grafman, J., Davis, M., Morrison, R., Hayes, J., Finley, S., Friedl, K., Fleischman, D., Arfanakis, K., James, O., Massoglia, D., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Alzheimer's Dis Neuroimaging In 2019; 10: 3310

  Abstract

  Alzheimer's disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.

  View details for DOI 10.1038/s41467-019-10945-z

  View details for Web of Science ID 000477017000003

  View details for PubMedID 31346172

  View details for PubMedCentralID PMC6658518

• Regional Amyloid-beta Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer's Dementia MOLECULAR NEUROBIOLOGY Schilling, L., Pascoal, T. A., Zimmer, E. R., Mathotaarachchi, S., Shin, M., de Mello Rieder, C., Gauthier, S., Palmini, A., Rosa-Neto, P., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Ances, B., Morris, J. C., Carroll, M., Creech, M. L., Franklin, E., Mintun, M. A., Schneider, S., Oliver, A., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Love, M., Grossman, H., Mitsis, E., Shah, R. C., deToledo-Morrell, L., Duara, R., Varon, D., Greig, M. T., Roberts, P., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Galvin, J. E., Cerbone, B., Michel, C. A., Pogorelec, D. M., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P., Petrella, J. R., Borges-Neto, S., Wong, T. Z., Coleman, E., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M., Brand, C., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Apostolova, L., Tingus, K., Woo, E., Silverman, D. S., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., Hunt, C., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, G., Feldman, H., Mudge, B., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Trost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C., Potkin, S. G., Preda, A., Nguyen, D., Tariot, P., Burke, A., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Gordineer, L., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pomara, N., Hernando, R., Sarrael, A., Relkin, N., Chaing, G., Lin, M., Ravdin, L., Smith, A., Raj, B., Fargher, K., Alzheimers Dis Neuroimaging 2019; 56 (7): 4916–24

  Abstract

  We investigated the association between amyloid-β deposition and white matter (WM) integrity as a determinant of brain glucose hypometabolism across the Alzheimer's disease (AD) spectrum. We assessed ninety-six subjects (27 cognitively normal, 49 mild cognitive impairment, and 20 AD dementia) who underwent [18F]FDG and [18F]Florbetapir positron emission tomography (PET) as well as magnetic resonance imaging (MRI) with diffusion tensor imaging. Among the regions with reduced fractional anisotropy (FA) in the AD group, we selected a voxel of interest in the angular bundle bilaterally for subsequent analyses. Using voxel-based interaction models at voxel level, we tested whether the regional hypometabolism is associated with FA in the angular bundle and regional amyloid-β deposition. In the AD patients, [18F]FDG hypometabolism in the striatum, mesiobasal temporal, orbitofrontal, precuneus, and cingulate cortices were associated with the interaction between high levels of [18F]Florbetapir standard uptake value ratios (SUVR) in these regions and low FA in the angular bundle. We found that the interaction between, rather than the independent effects of, high levels of amyloid-β deposition and WM integrity disruption determined limbic hypometabolism in patients with AD. This finding highlights a more integrative model for AD, where the interaction between partially independent processes determines the glucose hypometabolism.

  View details for DOI 10.1007/s12035-018-1405-1

  View details for Web of Science ID 000483159700024

  View details for PubMedID 30414086

• The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory NATURE COMMUNICATIONS Franzmeier, N., Rubinski, A., Neitzel, J., Ewers, M., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Logovinsky, V., Lilly, E., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakle, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Dana Nguyen, Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskin, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., Alzheimers Dis Neuroimaging Initia 2019; 10: 1766

  Abstract

  The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer's disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II-VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology.

  View details for DOI 10.1038/s41467-019-09564-5

  View details for Web of Science ID 000464654700005

  View details for PubMedID 30992433

  View details for PubMedCentralID PMC6467911

• White matter in different regions evolves differently during progression to dementia NEUROBIOLOGY OF AGING Dadar, M., Maranzano, J., Ducharme, S., Collins, D., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Witbracht, M., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Friedl, K., Hayes, J., Finley, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 76: 71–79

  Abstract

  White matter hyperintensities (WMHs) are common in individuals with mild cognitive impairment (MCI) and Alzheimer's disease. Patients with MCI with high WMH volumes are known to have an increased chance of conversion to Alzheimer's disease compared with those without WMHs. In this article, we assess the differences between patients with MCI that remain stable (N = 413) and those that progress to dementia (N = 178) in terms of WMH volume (as a surrogate of amount of tissue damage) and T1-weighted (T1w) image hypointensity (as a surrogate of severity of tissue damage) in periventricular, deep, and juxtacortical brain regions. Together, lesion volume and T1w hypointensity are used as a surrogate of vascular disease burden. Our results show a significantly greater increase of all regional WMH volumes in the MCI population that converts to dementia (p < 0.001). T1w hypointensity for the juxtacortical WMHs was significantly lower in the converter group (p < 0.0001) and was not affected by age. Conversely, T1w hypointensity in other regions showed a significant decrease with age (p < 0.0001). Within the converters, Time2Conversion was associated with both WMH volume and T1w hypointensity (p < 0.0001), and conversion to dementia was significantly associated with decreased intensity (and not volume) of periventricular and juxtacortical WMHs (p < 0.001). These changes differ according to the WM region, suggesting that different mechanisms affect the juxtacortical area in comparison to deep and periventricular regions in the process of conversion to dementia.

  View details for DOI 10.1016/j.neurobiolaging.2018.12.004

  View details for Web of Science ID 000459500800009

  View details for PubMedID 30703628

• A blood-based signature of cerebrospinal fluid A beta(1-42) status SCIENTIFIC REPORTS Goudey, B., Fung, B. J., Schieber, C., Faux, N. G., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Ances, B., Morris, J. C., Carroll, M., Creech, M. L., Franklin, E., Mintun, M. A., Schneider, S., Oliver, A., Marson, D., Griffth, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Love, M., Grossman, H., Mitsis, E., Shah, R. C., deToledo-Morrell, L., Duara, R., Varon, D., Greig, M. T., Roberts, P., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Galvin, J. E., Cerbone, B., Michel, C. A., Pogorelec, D. M., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P., Petrella, J. R., Borges-Neto, S., Wong, T. Z., Coleman, E., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M., Brand, C., Mulnard, R. A., Thai, G., McAdams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Apostolova, L., Tingus, K., Woo, E., Silverman, D. S., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parftt, F., Kendall, T., Johnson, H., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., Hunt, C., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, G., Feldman, H., Mudge, B., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Trost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Potkin, S. G., Preda, A., Nguyen, D., Tariot, P., Burke, A., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Gordineer, L., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pomara, N., Hernando, R., Sarrael, A., Relkin, N., Chaing, G., Lin, M., Ravdin, L., Smith, A., Raj, B., Fargher, K., Saykin, A., Nho, K., Kling, M., Toledo, J., Shaw, L., Trojanowski, J., Farrer, L., Kastsenmueller, G., Arnold, M., Wishart, D., Wurtz, P., Bhattcharyya, S., van Duijin, C., Mangravite, L., Han, X., Hankemeier, T., Fiehn, O., Barupal, D., Thiele, I., Heinken, A., Meikle, P., Price, N., Funk, C., Jia, W., Kueider-Paisley, A., Tenebaum, J., Black, C., Moseley, A., Thompson, W., Mahmoudiandehkorki, S., Baillie, R., Welsh-Bohmer, K., Plassman, B., Alzheimers Dis Metabol Consortium, Alzheimers Dis Neuroimaging Initia 2019; 9: 4163

  Abstract

  It is increasingly recognized that Alzheimer's disease (AD) exists before dementia is present and that shifts in amyloid beta occur long before clinical symptoms can be detected. Early detection of these molecular changes is a key aspect for the success of interventions aimed at slowing down rates of cognitive decline. Recent evidence indicates that of the two established methods for measuring amyloid, a decrease in cerebrospinal fluid (CSF) amyloid β1-42 (Aβ1-42) may be an earlier indicator of Alzheimer's disease risk than measures of amyloid obtained from Positron Emission Tomography (PET). However, CSF collection is highly invasive and expensive. In contrast, blood collection is routinely performed, minimally invasive and cheap. In this work, we develop a blood-based signature that can provide a cheap and minimally invasive estimation of an individual's CSF amyloid status using a machine learning approach. We show that a Random Forest model derived from plasma analytes can accurately predict subjects as having abnormal (low) CSF Aβ1-42 levels indicative of AD risk (0.84 AUC, 0.78 sensitivity, and 0.73 specificity). Refinement of the modeling indicates that only APOEε4 carrier status and four plasma analytes (CGA, Aβ1-42, Eotaxin 3, APOE) are required to achieve a high level of accuracy. Furthermore, we show across an independent validation cohort that individuals with predicted abnormal CSF Aβ1-42 levels transitioned to an AD diagnosis over 120 months significantly faster than those with predicted normal CSF Aβ1-42 levels and that the resulting model also validates reasonably across PET Aβ1-42 status (0.78 AUC). This is the first study to show that a machine learning approach, using plasma protein levels, age and APOEε4 carrier status, is able to predict CSF Aβ1-42 status, the earliest risk indicator for AD, with high accuracy.

  View details for DOI 10.1038/s41598-018-37149-7

  View details for Web of Science ID 000460755200011

  View details for PubMedID 30853713

• A review of statistical methods in imaging genetics CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE Nathoo, F. S., Kong, L., Zhu, H., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Mackin, S., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., Alzheimer's Dis Neuroimaging Initi 2019; 47 (1): 108–31

  View details for DOI 10.1002/cjs.11487

  View details for Web of Science ID 000459636600007

• A concise and persistent feature to study brain resting-state network dynamics: Findings from the Alzheimer's Disease Neuroimaging Initiative HUMAN BRAIN MAPPING Kuang, L., Han, X., Chen, K., Caselli, R. J., Reiman, E. M., Wang, Y., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Witbracht, M., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Friedl, K., Hayes, J., Finley, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 40 (4): 1062–81

  Abstract

  Alzheimer's disease (AD) is the most common type of dementia in the elderly with no effective treatment currently. Recent studies of noninvasive neuroimaging, resting-state functional magnetic resonance imaging (rs-fMRI) with graph theoretical analysis have shown that patients with AD and mild cognitive impairment (MCI) exhibit disrupted topological organization in large-scale brain networks. In previous work, it is a common practice to threshold such networks. However, it is not only difficult to make a principled choice of threshold values, but also worse is the discard of potential important information. To address this issue, we propose a threshold-free feature by integrating a prior persistent homology-based topological feature (the zeroth Betti number) and a newly defined connected component aggregation cost feature to model brain networks over all possible scales. We show that the induced topological feature (Integrated Persistent Feature) follows a monotonically decreasing convergence function and further propose to use its slope as a concise and persistent brain network topological measure. We apply this measure to study rs-fMRI data from the Alzheimer's Disease Neuroimaging Initiative and compare our approach with five other widely used graph measures across five parcellation schemes ranging from 90 to 1,024 region-of-interests. The experimental results demonstrate that the proposed network measure shows more statistical power and stronger robustness in group difference studies in that the absolute values of the proposed measure of AD are lower than MCI and much lower than normal controls, providing empirical evidence for decreased functional integration in AD dementia and MCI.

  View details for DOI 10.1002/hbm.24383

  View details for Web of Science ID 000459470400002

  View details for PubMedID 30569583

• Robust Motion Regression of Resting-State Data Using a Convolutional Neural Network Model FRONTIERS IN NEUROSCIENCE Yang, Z., Zhuang, X., Sreenivasan, K., Mishra, V., Cordes, D., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Witbracht, M., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Friedl, K., Hayes, J., Finley, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 13

  View details for DOI 10.3389/fnins.2019.00169

  View details for Web of Science ID 000459854900001

• The Relationship Between Hippocampal Volumes and Delayed Recall Is Modified by APOE epsilon 4 in Mild Cognitive Impairment FRONTIERS IN AGING NEUROSCIENCE Wang, X., Zhou, W., Ye, T., Lin, X., Zhang, J., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Logovinsky, V., Lilly, E., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Bodge, C., Weiner, M. W., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., Alzheimer's Dis Neuroimaging Initi 2019; 11

  View details for DOI 10.3389/fnagi.2019.00036

  View details for Web of Science ID 000459720800001

• Evaluating trajectories of episodic memory in normal cognition and mild cognitive impairment: Results from ADNI PLOS ONE Ding, X., Charnigo, R. J., Schmitt, F. A., Kryscio, R. J., Abner, E. L., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Mackin, S., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., Alzheimer's Dis Neuroimaging Initi 2019; 14 (2): e0212435

  Abstract

  Memory assessment is a key factor for the diagnosis of cognitive impairment. However, memory performance over time may be quite heterogeneous within diagnostic groups.To identify latent trajectories in memory performance and their associated risk factors, we analyzed data from Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who were classified either as cognitively normal or as Mild Cognitive Impairment (MCI) at baseline and were administered the Rey Auditory Verbal Learning test (RAVLT) for up to 9 years. Group-based trajectory modeling on the 30-minute RAVLT delayed recall score was applied separately to the two baseline diagnostic groups.There were 219 normal subjects with mean age 75.9 (range from 59.9 to 89.6) and 52.5% male participants, and 372 MCI subjects with mean age 74.8 (range from 55.1 to 89.3) and 63.7% male participants included in the analysis. For normal subjects, six trajectories were identified. Trajectories were classified into three types, determined by the shape, each of which may comprise more than one trajectory: stable (~30% of subjects), curvilinear decline (~ 28%), and linear decline (~ 42%). Notably, none of the normal subjects assigned to the stable stratum progressed to dementia during the study period. In contrast, all trajectories identified for the MCI group tended to decline, although some participants were later re-diagnosed with normal cognition. Age, sex, and education were significantly associated with trajectory membership for both diagnostic groups, while APOE ɛ4 was only significantly associated with trajectories among MCI participants.Memory trajectory is a strong indicator of dementia risk. If likely trajectory of memory performance can be identified early, such work may allow clinicians to monitor or predict progression of individual patient cognition. This work also shows the importance of longitudinal cognitive testing and monitoring.

  View details for DOI 10.1371/journal.pone.0212435

  View details for Web of Science ID 000459710700013

  View details for PubMedID 30802256

  View details for PubMedCentralID PMC6389289

• Longitudinal Brain Atrophy Rates in Transient Ischemic Attack and Minor Ischemic Stroke Patients and Cognitive Profiles FRONTIERS IN NEUROLOGY Munir, M., Ursenbach, J., Reid, M., Sah, R., Wang, M., Sitaram, A., Aftab, A., Tariq, S., Zamboni, G., Griffanti, L., Smith, E. E., Frayne, R., Sajobi, T. T., Coutts, S. B., d'Esterre, C. D., Barber, P. A., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hayes, J., Finley, S., Landau, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 10

  View details for DOI 10.3389/fneur.2019.00018

  View details for Web of Science ID 000459140700001

• Predicting Short-term MCI-to-AD Progression Using Imaging, CSF, Genetic Factors, Cognitive Resilience, and Demographics SCIENTIFIC REPORTS Varatharajah, Y., Ramanan, V. K., Iyer, R., Vemuri, P., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Saykin, A. J., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Schwartz, A., Montine, T., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Balasubramanian, A. B., Mason, J., Sim, I., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Faber, K., Kim, S., Nho, K., Thal, L., Buckholtz, N., Albert, M., Frank, R., Hsiao, J., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Pavlik, V., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Ances, B., Carroll, M., Creech, M. L., Franklin, E., Mintun, M. A., Schneider, S., Oliver, A., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Roberson, E., Grossman, H., Mitsis, E., Shah, R. C., deToledo-Morrell, L., Duara, R., Greig-Custo, M. T., Barker, W., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., Borges-Neto, S., Wong, T. Z., Coleman, E., Arnold, S. E., Karlawish, J. H., Wolk, D. A., Clark, C. M., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M., Brand, C., Preda, A., Nguyen, D., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Apostolova, L., Tingus, K., Woo, E., Silverman, D. S., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Rogers, J., Trost, D., Kertesz, A., Bernick, C., Munic, D., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Milliken, A., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Kelly, B., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Gordineer, L., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Tremont, G., Daiello, L. A., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Smith, K., Koleva, H., Nam, K., Shim, H., Relkin, N., Chaing, G., Lin, M., Ravdin, L., Smith, A., Raj, B., Fargher, K., Alzheimers Dis Neuroimaging Initia 2019; 9: 2235

  Abstract

  In the Alzheimer's disease (AD) continuum, the prodromal state of mild cognitive impairment (MCI) precedes AD dementia and identifying MCI individuals at risk of progression is important for clinical management. Our goal was to develop generalizable multivariate models that integrate high-dimensional data (multimodal neuroimaging and cerebrospinal fluid biomarkers, genetic factors, and measures of cognitive resilience) for identification of MCI individuals who progress to AD within 3 years. Our main findings were i) we were able to build generalizable models with clinically relevant accuracy (~93%) for identifying MCI individuals who progress to AD within 3 years; ii) markers of AD pathophysiology (amyloid, tau, neuronal injury) accounted for large shares of the variance in predicting progression; iii) our methodology allowed us to discover that expression of CR1 (complement receptor 1), an AD susceptibility gene involved in immune pathways, uniquely added independent predictive value. This work highlights the value of optimized machine learning approaches for analyzing multimodal patient information for making predictive assessments.

  View details for DOI 10.1038/s41598-019-38793-3

  View details for Web of Science ID 000459092800005

  View details for PubMedID 30783207

  View details for PubMedCentralID PMC6381141

• Diffusion MRI Indices and Their Relation to Cognitive Impairment in Brain Aging: The Updated Multi-protocol Approach in ADNI3 FRONTIERS IN NEUROINFORMATICS Zavaliangos-Petropulu, A., Nir, T. M., Thomopoulos, S., Reid, R., Bernstein, M. A., Borowski, B., Jack, C. R., Weiner, M. W., Jahanshad, N., Thompson, P. M., Aisen, P., Weiner, M., Petersen, R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Witbracht, M., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Friedl, K., Hayes, J., Finley, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 13

  View details for DOI 10.3389/fninf.2019.00002

  View details for Web of Science ID 000459087800001

• Association of CSF CD40 levels and synaptic degeneration across the Alzheimer's disease spectrum NEUROSCIENCE LETTERS Ye, X., Zhou, W., Zhang, J., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Witbracht, M., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Friedl, K., Hayes, J., Finley, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 694: 41–45

  Abstract

  The CD40 pathway has been implicated in microglial activation, which is considered as a key factor in the pathogenesis of Alzheimer's disease (AD). However, the association of CSF CD40 and synaptic degeneration in living human is not clear. A total of 294 subjects with different severities of cognitive impairments were included in this study: 84 participants with normal cognition, 143 patients with mild cognitive impairment (MCI) and 67 patients with mild AD. Levels of CD40 in CSF were compared among the three groups. Further, several linear regression models were conducted to explore the associations of CSF CD40 and neurogranin levels (reflecting synaptic degeneration) when controlling for age, gender, educational attainment, APOE4 genotype, clinical diagnosis, CSF Aβ42 and tau proteins. We found that CSF CD40 levels were significantly decreased in patients with mild AD compared with healthy controls and MCI patients (control vs. AD, p = 0.0026; MCI vs. AD, p = 0.0268). However, there were no significant differences in CSF CD40 levels between controls and patients with MCI (p = 0.37). In addition, CSF CD40 levels were associated with neurogranin in the pooled sample when controlling for age, gender, educational attainment, APOE4 genotype and diagnosis. In summary, our findings support the notion that the CD40 pathway may contribute to an important mechanism underlying synaptic degeneration in AD.

  View details for DOI 10.1016/j.neulet.2018.11.019

  View details for Web of Science ID 000459643800007

  View details for PubMedID 30447377

• MAPT rs242557 variant is associated with hippocampus tau uptake on F-18-AV-1451 PET in non-demented elders AGING-US Shen, X., Miao, D., Li, J., Tan, C., Cao, X., Tan, L., Yu, J., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Witbracht, M., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Friedl, K., Hayes, J., Finley, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 11 (3): 874–84

  Abstract

  The microtubule-associated protein tau gene (MAPT) rs242557 variant is associated with multiple tauopathies and dementia. This study investigated whether it was correlated with brain tau-PET uptake in non-demented elders. Ninety non-demented elders were identified from the Alzheimer's Disease Neuroimaging Initiative cohort. We compared standardized uptake value ratios (SUVRs) of tau-PET tracer 18F-AV-1451 between rs242557 variant carriers and non-carriers in 25 regions of interest (ROIs). The minor allele A was associated with increased hippocampus 18F-AV-1451 uptake in non-demented elders (left: β = 0.111, Bonferroni corrected p = 0.035; right: β = 0.103, Bonferroni corrected p = 0.031). Aβ-positive participants (left: β = 0.206, Bonferroni corrected p = 0.029; right: β = 0.198, Bonferroni corrected p = 0.035) and APOE ε4 non-carriers (left: β = 0.140, Bonferroni corrected p = 0.006; right: β = 0.134, Bonferroni corrected p = 0.004) exhibited approximately the same findings in hippocampus. Considering no obvious associations in other regions, we confirmed the significant correlation of MAPT rs242557 risk variant with increased hippocampus tau deposition in non-demented elders. With higher magnitude signals in the hippocampus that is more likely to be uniquely affected in AD, the tau PET ligand 18F-AV-1451 seemed to possess a specific binding property for AD-like tau pathology.

  View details for DOI 10.18632/aging.101783

  View details for Web of Science ID 000459482200011

  View details for PubMedID 30708351

  View details for PubMedCentralID PMC6382414

• Random forest prediction of Alzheimer's disease using pairwise selection from time series data PLOS ONE Moore, P. J., Lyons, T. J., Gallacher, J., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Donohue, M., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Buckholtz, N., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Harless, K., Hayes, J., Finley, S., Householder, E., Lee, V., Korecka, M., Figurski, M., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Fleischman, D., Arfanakis, K., Shah, R. C., Varon, D., Martin, K. S., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Jagust, W., Landau, S., Rosen, H., Perry, D., Behan, K., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Wolday, S., Allard, J., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Furst, A. J., Relkin, N., Chiang, G., Ravdin, L., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Nudelman, K. N., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Init 2019; 14 (2): e0211558

  Abstract

  Time-dependent data collected in studies of Alzheimer's disease usually has missing and irregularly sampled data points. For this reason time series methods which assume regular sampling cannot be applied directly to the data without a pre-processing step. In this paper we use a random forest to learn the relationship between pairs of data points at different time separations. The input vector is a summary of the time series history and it includes both demographic and non-time varying variables such as genetic data. To test the method we use data from the TADPOLE grand challenge, an initiative which aims to predict the evolution of subjects at risk of Alzheimer's disease using demographic, physical and cognitive input data. The task is to predict diagnosis, ADAS-13 score and normalised ventricles volume. While the competition proceeds, forecasting methods may be compared using a leaderboard dataset selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and with standard metrics for measuring accuracy. For diagnosis, we find an mAUC of 0.82, and a classification accuracy of 0.73 compared with a benchmark SVM predictor which gives mAUC = 0.62 and BCA = 0.52. The results show that the method is effective and comparable with other methods.

  View details for DOI 10.1371/journal.pone.0211558

  View details for Web of Science ID 000458763900015

  View details for PubMedID 30763336

  View details for PubMedCentralID PMC6375557

• Predicting Alzheimer's disease progression using multi-modal deep learning approach SCIENTIFIC REPORTS Lee, G., Nho, K., Kang, B., Sohn, K., Kim, D., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Thomas, R. G., Donohue, M., Walter, S., Sather, T., Jiminez, G., Balasubramanian, A. B., Mason, J., Sim, I., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Cairns, N. J., Householder, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Tha, L., Frank, R., Hsiao, J., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Ances, B., Carroll, M., Creech, M. L., Franklin, E., Mintun, M. A., Schneider, S., Oliver, A., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Love, M., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Grossman, H., Mitsis, E., Shah, R. C., deToledo-Morrell, L., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Duara, R., Varon, D., Greig, M. T., Roberts, P., Stern, Y., Honig, L. S., Bell, K. L., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Galvin, J. E., Cerbone, B., Michel, C. A., Pogorelec, D. M., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Womack, K., Mathews, D., Quiceno, M., Doraiswamy, P., Petrella, J. R., Borges-Neto, S., Wong, T. Z., Coleman, E., Levey, A. I., Lah, J. J., Cella, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Arnold, S. E., Karlawish, J. H., Wolk, D., Clark, C. M., Apostolova, L., Tingus, K., Woo, E., Silverman, D. S., Lu, P. H., Bartzokis, G., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., Lopez, O. L., Oakley, M., Simpson, D. M., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., Hunt, C., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M., Brand, C., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, G., Feldman, H., Mudge, B., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Trost, D., Kertesz, A., Bernick, C., Munic, D., Lipowski, K., Weintraub, M., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Preda, A., Nguyen, D., Tariot, P., Burke, A., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Gordineer, L., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Ponto, L., Shim, H., Smith, K., Relkin, N., Chaing, G., Lin, M., Ravdin, L., Smith, A., Raj, B., Fargher, K., Alzheimer's Dis Neuroimaging Initi 2019; 9: 1952

  Abstract

  Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI). The proposed framework integrated longitudinal multi-domain data. Our results showed that 1) our prediction model for MCI conversion to AD yielded up to 75% accuracy (area under the curve (AUC) = 0.83) when using only single modality of data separately; and 2) our prediction model achieved the best performance with 81% accuracy (AUC = 0.86) when incorporating longitudinal multi-domain data. A multi-modal deep learning approach has potential to identify persons at risk of developing AD who might benefit most from a clinical trial or as a stratification approach within clinical trials.

  View details for DOI 10.1038/s41598-018-37769-z

  View details for Web of Science ID 000458572500013

  View details for PubMedID 30760848

  View details for PubMedCentralID PMC6374429

• QuickNAT: A fully convolutional network for quick and accurate segmentation of neuroanatomy NEUROIMAGE Roy, A., Conjeti, S., Navab, N., Wachinger, C., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCarli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., Riham El Khouli, Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Dros, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hergesheimen, L., Hayes, J., Finley, S., Landau, S., Cairns, N. J., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 186: 713–27

  Abstract

  Whole brain segmentation from structural magnetic resonance imaging (MRI) is a prerequisite for most morphological analyses, but is computationally intense and can therefore delay the availability of image markers after scan acquisition. We introduce QuickNAT, a fully convolutional, densely connected neural network that segments a MRI brain scan in 20 s. To enable training of the complex network with millions of learnable parameters using limited annotated data, we propose to first pre-train on auxiliary labels created from existing segmentation software. Subsequently, the pre-trained model is fine-tuned on manual labels to rectify errors in auxiliary labels. With this learning strategy, we are able to use large neuroimaging repositories without manual annotations for training. In an extensive set of evaluations on eight datasets that cover a wide age range, pathology, and different scanners, we demonstrate that QuickNAT achieves superior segmentation accuracy and reliability in comparison to state-of-the-art methods, while being orders of magnitude faster. The speed up facilitates processing of large data repositories and supports translation of imaging biomarkers by making them available within seconds for fast clinical decision making.

  View details for DOI 10.1016/j.neuroimage.2018.11.042

  View details for Web of Science ID 000455968400064

  View details for PubMedID 30502445

• Communicability disruption in Alzheimer's disease connectivity networks JOURNAL OF COMPLEX NETWORKS Lella, E., Amoroso, N., Lombardi, A., Maggipinto, T., Tangaro, S., Bellotti, R., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Logovinsky, V., Lilly, E., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakle, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Dana Nguyen, Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskin, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., Alzheimers Dis Neuroimaging Initia 2019; 7 (1): 83–100

  View details for DOI 10.1093/comnet/cny009

  View details for Web of Science ID 000458284700004

• Functional signature of conversion of patients with mild cognitive impairment NEUROBIOLOGY OF AGING Pizzi, S., Punzi, M., Sensi, S. L., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Logovinsky, V., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCarli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., Van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Jack, C. R., Neylan, T., Grafman, J., Hergesheimen, L., Hayes, J., Finley, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W. R., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffe, E. R., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Alzheimers Dis Neuroimaging Initia 2019; 74: 21–37

  Abstract

  The entorhinal-hippocampal circuit is a strategic hub for cognition and the first site affected by Alzheimer's disease (AD). We investigated magnetic resonance imaging patterns of brain atrophy and functional connectivity in an Alzheimer's Disease Neuroimaging Initiative data set that included healthy controls, mild cognitive impairment (MCI), and patients with AD. Individuals with MCI were clinically evaluated 24 months after the first magnetic resonance imaging scan, and the cohort subdivided into sets of individuals who either did or did not convert to AD. The MCI group was also divided into patients who did show or not the presence of AD-related alterations in the cerebrospinal fluid. Patients with AD exhibited the collapse of the long-range hippocampal/entorhinal connectivity, pronounced cortical/subcortical atrophy, and a dramatic decline in cognitive performances. Patients with MCI who converted to AD or patients with MCI who showed the presence of AD-related alterations in the cerebrospinal fluid showed memory deficits, entorhinal/hippocampal hypoconnectivity, and concomitant atrophy of the two regions. Patients with MCI who did not convert to AD or patients with MCI who did not show the presence of AD-related alterations in the cerebrospinal fluid had no atrophy but showed hippocampal/entorhinal hyperconnectivity with selected neocortical/subcortical regions involved in memory processing and brain metastability. This hyperconnectivity may represent a compensatory strategy against the progression of cognitive impairment.

  View details for DOI 10.1016/j.neurobiolaging.2018.10.004

  View details for Web of Science ID 000455193900003

  View details for PubMedID 30408719

• Translating Alzheimer's disease-associated polymorphisms into functional candidates: a survey of IGAP genes and SNPs NEUROBIOLOGY OF AGING Katsumata, Y., Nelson, P. T., Estus, S., Fardo, D. W., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hergesheimen, L., Hayes, J., Finley, S., Landau, S., Cairns, N. J., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 74: 135–46

  Abstract

  The International Genomics of Alzheimer's Project (IGAP) is a consortium for characterizing the genetic landscape of Alzheimer's disease (AD). The identified and/or confirmed 19 single-nucleotide polymorphisms (SNPs) associated with AD are located on non-coding DNA regions, and their functional impacts on AD are as yet poorly understood. We evaluated the roles of the IGAP SNPs by integrating data from many resources, based on whether the IGAP SNP was (1) a proxy for a coding SNP or (2) associated with altered mRNA transcript levels. For (1), we confirmed that 12 AD-associated coding common SNPs and five nonsynonymous rare variants are in linkage disequilibrium with the IGAP SNPs. For (2), the IGAP SNPs in CELF1 and MS4A6A were associated with expression of their neighboring genes, MYBPC3 and MS4A6A, respectively, in blood. The IGAP SNP in DSG2 was an expression quantitative trait loci (eQTL) for DLGAP1 and NETO1 in the human frontal cortex. The IGAP SNPs in ABCA7, CD2AP, and CD33 each acted as eQTL for AD-associated genes in brain. Our approach for identifying proxies and examining eQTL highlighted potentially impactful, novel gene regulatory phenomena pertinent to the AD phenotype.

  View details for DOI 10.1016/j.neurobiolaging.2018.10.017

  View details for Web of Science ID 000455193900013

  View details for PubMedID 30448613

  View details for PubMedCentralID PMC6331247

• Amyloid beta-positive subjects exhibit longitudinal network-specific reductions in spontaneous brain activity NEUROBIOLOGY OF AGING Avants, B. B., Hutchison, R., Mikulskis, A., Salinas-Valenzuela, C., Hargreaves, R., Beaver, J., Chiao, P., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCarli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., Van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., Demarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hayes, J., Finley, S., Landau, S., Cairns, N. J., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W. R., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 74: 191–201

  Abstract

  Amyloid beta (Aβ) deposition and cognitive decline are key features of Alzheimer's disease. The relationship between Aβ status and changes in neuronal function over time, however, remains unclear. We evaluated the effect of baseline Aβ status on reference region spontaneous brain activity (SBA-rr) using resting-state functional magnetic resonance imaging and fluorodeoxyglucose positron emission tomography in patients with mild cognitive impairment. Patients (N = 62, [43 Aβ-positive]) from the Alzheimer's Disease Neuroimaging Initiative were divided into Aβ-positive and Aβ-negative groups via prespecified cerebrospinal fluid Aβ42 or 18F-florbetapir positron emission tomography standardized uptake value ratio cutoffs measured at baseline. We analyzed interaction of biomarker-confirmed Aβ status with SBA-rr change over a 2-year period using mixed-effects modeling. SBA-rr differences between Aβ-positive and Aβ-negative subjects increased significantly over time within subsystems of the default and visual networks. Changes exhibit an interaction with memory performance over time but were independent of glucose metabolism. Results reinforce the value of resting-state functional magnetic resonance imaging in evaluating Alzheimer''s disease progression and suggest spontaneous neuronal activity changes are concomitant with cognitive decline.

  View details for DOI 10.1016/j.neurobiolaging.2018.10.002

  View details for Web of Science ID 000455193900018

  View details for PubMedID 30471630

• A Novel Method to Estimate Long-Term Chronological Changes From Fragmented Observations in Disease Progression CLINICAL PHARMACOLOGY & THERAPEUTICS Ishida, T., Tokuda, K., Hisaka, A., Honma, M., Kijima, S., Takatoku, H., Iwatsubo, T., Moritoyo, T., Suzuki, H., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hayes, J., Finley, S., Landau, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging 2019; 105 (2): 436–47

  Abstract

  Clinical observations of patients with chronic diseases are often restricted in terms of duration. Therefore, obtaining a quantitative and comprehensive understanding of the chronology of chronic diseases is challenging, because of the inability to precisely estimate the patient's disease stage at the time point of observation. We developed a novel method to reconstitute long-term disease progression from temporally fragmented data by extending the nonlinear mixed-effects model to incorporate the estimation of "disease time" of each subject. Application of this method to sporadic Alzheimer's disease successfully depicted disease progression over 20 years. The covariate analysis revealed earlier onset of amyloid-β accumulation in male and female apolipoprotein E ε4 homozygotes, whereas disease progression was remarkably slower in female ε3 homozygotes compared with female ε4 carriers and males. Simulation of a clinical trial suggests patient recruitment using the information of precise disease time of each patient will decrease the sample size required for clinical trials.

  View details for DOI 10.1002/cpt.1166

  View details for Web of Science ID 000457465200029

  View details for PubMedID 29951994

• Medical Image Imputation From Image Collections IEEE TRANSACTIONS ON MEDICAL IMAGING Dalca, A. V., Bouman, K. L., Freeman, W. T., Rost, N. S., Sabuncu, M. R., Golland, P., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshal, G., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Mackin, S., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., Alzheimer's Dis Neuroimaging Initi 2019; 38 (2): 504–14

  Abstract

  We present an algorithm for creating high resolution anatomically plausible images consistent with acquired clinical brain MRI scans with large inter-slice spacing. Although large data sets of clinical images contain a wealth of information, time constraints during acquisition result in sparse scans that fail to capture much of the anatomy. These characteristics often render computational analysis impractical as many image analysis algorithms tend to fail when applied to such images. Highly specialized algorithms that explicitly handle sparse slice spacing do not generalize well across problem domains. In contrast, we aim to enable application of existing algorithms that were originally developed for high resolution research scans to significantly undersampled scans. We introduce a generative model that captures fine-scale anatomical structure across subjects in clinical image collections and derive an algorithm for filling in the missing data in scans with large inter-slice spacing. Our experimental results demonstrate that the resulting method outperforms state-of-the-art upsampling super-resolution techniques, and promises to facilitate subsequent analysis not previously possible with scans of this quality. Our implementation is freely available at https://github.com/adalca/papago.

  View details for DOI 10.1109/TMI.2018.2866692

  View details for Web of Science ID 000457604700017

  View details for PubMedID 30136936

• Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers ALZHEIMERS & DEMENTIA Nho, K., Kueider-Paisley, A., MahmoudianDehkordi, S., Arnold, M., Risacher, S. L., Louie, G., Blach, C., Baillie, R., Han, X., Kastenmueller, G., Jia, W., Xie, G., Ahmad, S., Hankemeier, T., van Duijn, C. M., Trojanowski, J. Q., Shaw, L. M., Weiner, M. W., Doraiswamy, P., Saykin, A. J., Kaddurah-Daouk, R., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Morris, J., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hayes, J., Finley, S., Landau, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia, Alzheimer Dis Metab Consortium 2019; 15 (2): 232–44

  Abstract

  Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer's disease (AD) including neuroinflammation and amyloid-β deposition.Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n = 1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD: cerebrospinal fluid (CSF) biomarkers, atrophy (magnetic resonance imaging), and brain glucose metabolism ([18F]FDG PET).Of 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSF Aβ1-42 ("A") and three with CSF p-tau181 ("T") (corrected P < .05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy ("N"), respectively (corrected P < .05).This is the first study to show serum-based BA metabolites are associated with "A/T/N" AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association.

  View details for PubMedID 30337152

• Accurate risk estimation of beta-amyloid positivity to identify prodromal Alzheimer's disease: Cross-validation study of practical algorithms ALZHEIMERS & DEMENTIA Palmqvist, S., Insel, P. S., Zetterberg, H., Blennow, K., Brix, B., Stomrud, E., Mattsson, N., Hansson, O., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Witbracht, M., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Carlsson, C. M., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Salloway, S., Malloy, P., Correia, S., Lee, A., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hergesheimen, L., Hayes, J., Finley, S., Householder, E., Friedl, K., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Li, G., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia, Swedish BioFINDER Study 2019; 15 (2): 194–204

  Abstract

  The aim was to create readily available algorithms that estimate the individual risk of β-amyloid (Aβ) positivity.The algorithms were tested in BioFINDER (n = 391, subjective cognitive decline or mild cognitive impairment) and validated in Alzheimer's Disease Neuroimaging Initiative (n = 661, subjective cognitive decline or mild cognitive impairment). The examined predictors of Aβ status were demographics; cognitive tests; white matter lesions; apolipoprotein E (APOE); and plasma Aβ42/Aβ40, tau, and neurofilament light.Aβ status was accurately estimated in BioFINDER using age, 10-word delayed recall or Mini-Mental State Examination, and APOE (area under the receiver operating characteristics curve = 0.81 [0.77-0.85] to 0.83 [0.79-0.87]). When validated, the models performed almost identical in Alzheimer's Disease Neuroimaging Initiative (area under the receiver operating characteristics curve = 0.80-0.82) and within different age, subjective cognitive decline, and mild cognitive impairment populations. Plasma Aβ42/Aβ40 improved the models slightly.The algorithms are implemented on http://amyloidrisk.com where the individual probability of being Aβ positive can be calculated. This is useful in the workup of prodromal Alzheimer's disease and can reduce the number needed to screen in Alzheimer's disease trials.

  View details for DOI 10.1016/j.jalz.2018.08.014

  View details for Web of Science ID 000457693500002

  View details for PubMedID 30365928

• Accuracy and generalization capability of an automatic method for the detection of typical brain hypometabolism in prodromal Alzheimer disease EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING De Carli, F., Nobili, F., Pagani, M., Bauckneht, M., Massa, F., Grazzini, M., Jonsson, C., Peira, E., Morbelli, S., Arnaldi, D., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Mackin, S., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., Alzheimer's Dis Neuroimaging Initi 2019; 46 (2): 334–47

  Abstract

  The aim of this study was to verify the reliability and generalizability of an automatic tool for the detection of Alzheimer-related hypometabolic pattern based on a Support-Vector-Machine (SVM) model analyzing 18F-fluorodeoxyglucose (FDG) PET data.The SVM model processed metabolic data from anatomical volumes of interest also considering interhemispheric asymmetries. It was trained on a homogeneous dataset from a memory clinic center and tested on an independent multicentric dataset drawn from the Alzheimer's Disease Neuroimaging Initiative. Subjects were included in the study and classified based on a diagnosis confirmed after an adequate follow-up time.The accuracy of the discrimination between patients with Alzheimer Disease (AD), in either prodromal or dementia stage, and normal aging subjects was 95.8%, after cross-validation, in the training set. The accuracy of the same model in the testing set was 86.5%. The role of the two datasets was then reversed, and the accuracy was 89.8% in the multicentric training set and 88.0% in the monocentric testing set. The classification rate was also evaluated in different subgroups, including non-converter mild cognitive impairment (MCI) patients, subjects with MCI reverted to normal conditions and subjects with non-confirmed memory concern. The percent of pattern detections increased from 77% in early prodromal AD to 91% in AD dementia, while it was about 10% for healthy controls and non-AD patients.The present findings show a good level of reproducibility and generalizability of a model for detecting the hypometabolic pattern in AD and confirm the accuracy of FDG-PET in Alzheimer disease.

  View details for DOI 10.1007/s00259-018-4197-7

  View details for Web of Science ID 000455817600009

  View details for PubMedID 30382303

• Disease progression timeline estimation for Alzheimer's disease using discriminative event based modeling NEUROIMAGE Venkatraghavan, V., Bron, E. E., Niessen, W. J., Klein, S., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Md, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hergesheimen, L., Hayes, J., Finley, S., Landau, S., Friedl, K., Cairns, N. J., Householder, E., Phd, V., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 186: 518–32

  Abstract

  Alzheimer's Disease (AD) is characterized by a cascade of biomarkers becoming abnormal, the pathophysiology of which is very complex and largely unknown. Event-based modeling (EBM) is a data-driven technique to estimate the sequence in which biomarkers for a disease become abnormal based on cross-sectional data. It can help in understanding the dynamics of disease progression and facilitate early diagnosis and prognosis by staging patients. In this work we propose a novel discriminative approach to EBM, which is shown to be more accurate than existing state-of-the-art EBM methods. The method first estimates for each subject an approximate ordering of events. Subsequently, the central ordering over all subjects is estimated by fitting a generalized Mallows model to these approximate subject-specific orderings based on a novel probabilistic Kendall's Tau distance. We also introduce the concept of relative distance between events which helps in creating a disease progression timeline. Subsequently, we propose a method to stage subjects by placing them on the estimated disease progression timeline. We evaluated the proposed method on Alzheimer's Disease Neuroimaging Initiative (ADNI) data and compared the results with existing state-of-the-art EBM methods. We also performed extensive experiments on synthetic data simulating the progression of Alzheimer's disease. The event orderings obtained on ADNI data seem plausible and are in agreement with the current understanding of progression of AD. The proposed patient staging algorithm performed consistently better than that of state-of-the-art EBM methods. Event orderings obtained in simulation experiments were more accurate than those of other EBM methods and the estimated disease progression timeline was observed to correlate with the timeline of actual disease progression. The results of these experiments are encouraging and suggest that discriminative EBM is a promising approach to disease progression modeling.

  View details for DOI 10.1016/j.neuroimage.2018.11.024

  View details for Web of Science ID 000455968400048

  View details for PubMedID 30471388

• Dual-Model Radiomic Biomarkers Predict Development of Mild Cognitive Impairment Progression to Alzheimer's Disease FRONTIERS IN NEUROSCIENCE Zhou, H., Jiang, J., Lu, J., Wang, M., Zhang, H., Zuo, C., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Logovinsky, V., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Landau, S., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stem, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Nlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hergesheimen, L., Hayes, J., Finley, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Dana Nguyen, Massoglia, D., Brawman-Mintzer, O., Martinez, W. R., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffe, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Reyes, D., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 12

  View details for DOI 10.3389/fnins.2018.01045

  View details for Web of Science ID 000455546700001

• Longitudinal Functional Brain Mapping in Supernormals CEREBRAL CORTEX Wang, X., Ren, P., Baran, T. M., Raizada, R. S., Mapstone, M., Lin, F., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Mackin, S., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., Alzheimers Dis Neuroimaging Initi 2019; 29 (1): 242–52

  Abstract

  Gene regulatory networks (GRNs) play an important role in cellular systems and are important for understanding biological processes. Many algorithms have been developed to infer the GRNs. However, most algorithms only pay attention to the gene expression data but do not consider the topology information in their inference process, while incorporating this information can partially compensate for the lack of reliable expression data. Here we develop a Bayesian group lasso with spike and slab priors to perform gene selection and estimation for nonparametric models. B-spline basis functions are used to capture the nonlinear relationships flexibly and penalties are used to avoid overfitting. Further, we incorporate the topology information into the Bayesian method as a prior. We present the application of our method on DREAM3 and DREAM4 datasets and two real biological datasets. The results show that our method performs better than existing methods and the topology information prior can improve the result.

  View details for DOI 10.1093/cercor/bhx322

  View details for Web of Science ID 000459518500019

  View details for PubMedID 28133490

  View details for PubMedCentralID PMC5241943

• Prediction and Classification of Alzheimer's Disease Based on Combined Features From Apolipoprotein-E Genotype, Cerebrospinal Fluid, MR, and FDG-PET Imaging Biomarkers. Frontiers in computational neuroscience Gupta, Y., Lama, R. K., Kwon, G., Alzheimer's Disease Neuroimaging Initiative, Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M. M., Potter, W., Snyder, P., Schwartz, A., Green, R. C., Montine, T., Petersen, R., Aisen, P., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Balasubramanian, A. B., Mason, J., Sim, I., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Pavlik, V., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Ances, B., Morris, J. C., Carroll, M., Creech, M. L., Franklin, E., Mintun, M. A., Schneider, S., Oliver, A., Marson, D., Geldmacher, D., Natelson Love, M., Griffith, R., Clark, D., Brockington, J., Roberson, E., Grossman, H., Mitsis, E., Shah, R. C., deToledo-Morrell, L., Duara, R., Greig-Custo, M. T., Barker, W., Albert, M., Onyike, C., D'Agostino, D. 2., Kielb, S., Sadowski, M., Sheikh, M. O., Anaztasia, U., Mrunalini, G., Doraiswamy, P. M., Petrella, J. R., Borges-Neto, S., Wong, T. Z., Coleman, E., Arnold, S. E., Karlawish, J. H., Wolk, D. A., Clark, C. M., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M. S., Brand, C., Potkin, S. G., Preda, A., Nguyen, D., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Apostolova, L., Tingus, K., Woo, E., Silverman, D. H., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A. M., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, G. R., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Trost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R. S., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Obisesan, T. O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Potkin, S. G., Preda, A., Nguyen, D., Tariot, P., Burke, A., Milliken, A. M., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Kelley, B., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Leslie, G., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Tremont, G., Daiello, L. A., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Smith, K. E., Koleva, H., Nam, K. W., Shim, H., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Raj, B. A., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Thomas, R. G., Donohue, M., Devon, G., Sather, T., Melissa, D., Morrison, R., Jiminez, G., Neylan, T., Jacqueline, H., Shannon, F., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kejal, K., Chad, W., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Karen, C., Scott, N., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Karl, F., Schneider, L. S., Pawluczyk, S., Mauricio, B., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P. M., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R. S., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J. J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Ravdin, L., Mackin, S., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y. H., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M. 2019; 13: 72

  Abstract

  Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.

  View details for DOI 10.3389/fncom.2019.00072

  View details for PubMedID 31680923

• A delta Homolog for Dementia Case Finding with Replication in the Alzheimer's Disease Neuroimaging Initiative JOURNAL OF ALZHEIMERS DISEASE Royall, D. R., Palmer, R. F., Weiner, M. W., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hayes, J., Finley, S., Landau, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Faber, K. M., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 67 (1): 67–79

  Abstract

  Dementia can be empirically described by the latent dementia phenotype "δ" and its various composite "homologs". We have explored δ's blood-based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. However, it would be convenient to replicate those associations in the Alzheimer's Disease Neuroimaging Initiative (ADNI). To this end, we have engineered a δ homolog from observed cognitive performance measures common to both projects. Our findings were replicated in randomly selected 50% splits of TARCC data (Group 1, N = 1,747; Group 2, N = 1,755), and then independently in ADNI (N = 1,737). The new δ homolog, i.e., "dT2A" (d-TARCC to ADNI), fit the data of both studies well, and was strongly correlated with dementia severity, as rated by the Clinical Dementia Rating Scale "sum of boxes" (TARCC: r = 0.99, p < 0.001; ADNI: r = 0.96, p < 0.001). dT2A achieved an area under the receiver operating characteristic curve of 0.981 (0.976-0.985) for the discrimination of Alzheimer's disease from normal controls in TARCC, and 0.988 (0.983-0.993) in ADNI. dT2A is the 12th δ homolog published to date, and opens the door to independent replications across these and similar studies.

  View details for PubMedID 30507569

• Next Generation Sequencing Analysis in Early Onset Dementia Patients JOURNAL OF ALZHEIMERS DISEASE Bonvicini, C., Scassellati, C., Benussi, L., Di Maria, E., Maj, C., Ciani, M., Fostinelli, S., Mega, A., Bocchetta, M., Lanzi, G., Giacopuzzi, E., Ferraboli, S., Pievani, M., Fedi, V., Defanti, C., Giliani, S., Frisoni, G., Ghidoni, R., Gennarelli, M., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Becerra, M., Landau, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Nlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., Demarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hergesheimen, L., Hayes, J., Finley, S., Householder, E., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W. R., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffe, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimers Dis Neuroimaging Initia 2019; 67 (1): 243–56

  Abstract

  Early onset dementias (EOD) are rare neurodegenerative dementias that present before 65 years. Genetic factors have a substantially higher pathogenetic contribution in EOD patients than in late onset dementia.To identify known and/or novel rare variants in major candidate genes associated to EOD by high-throughput sequencing. Common-risk variants of apolipoprotein E (APOE) and prion protein (PRNP) genes were also assessed.We studied 22 EOD patients recruited in Memory Clinics, in the context of studies investigating genetic forms of dementia. Two methodological approaches were applied for the target-Next Generation Sequencing (NGS) analysis of these patients. In addition, we performed progranulin plasma dosage, C9Orf72 hexanucleotide repeat expansion analysis, and APOE genotyping.We detected three rare known pathogenic mutations in the GRN and PSEN2 genes and eleven unknown-impact mutations in the GRN, VCP, MAPT, FUS, TREM2, and NOTCH3 genes. Six patients were carriers of only common risk variants (APOE and PRNP), and one did not show any risk mutation/variant. Overall, 69% (n = 9) of our early onset Alzheimer's disease (EAOD) patients, compared with 34% (n = 13) of sporadic late onset Alzheimer's disease (LOAD) patients and 27% (n = 73) of non-affected controls (ADNI, whole genome data), were carriers of at least two rare/common risk variants in the analyzed candidate genes panel, excluding the full penetrant mutations.This study suggests that EOD patients without full penetrant mutations are characterized by higher probability to carry polygenic risk alleles that patients with LOAD forms. This finding is in line with recently reported evidence, thus suggesting that the genetic risk factors identified in LOAD might modulate the risk also in EOAD.

  View details for DOI 10.3233/JAD-180482

  View details for Web of Science ID 000457778000020

  View details for PubMedID 30530974

• Understanding disease progression and improving Alzheimer's disease clinical trials: Recent highlights from the Alzheimer's Disease Neuroimaging Initiative ALZHEIMERS & DEMENTIA Veitch, D. P., Weiner, M. W., Aisen, P. S., Beckett, L. A., Cairns, N. J., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Petersen, R. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowski, J. Q., Aisen, P., Weiner, M., Petersen, R., Trojanowki, J. Q., Toga, A. W., Beckett, L., Morris, J., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Hsiung, C., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hergesheimen, L., Hayes, J., Finley, S., Householder, E., Friedl, K., Fleischman, D., Arfanakis, K., Varon, D., Greig, M. T., Porsteinsso, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Landau, S., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Li, G., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Yesavage, J. A., Furst, A. J., Alzheimers Dis Neuroimaging Ini 2019; 15 (1): 106–52

  Abstract

  The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI is a multisite, longitudinal, observational study that has collected many biomarkers since 2004. Recent publications highlight the multifactorial nature of late-onset AD. We discuss selected topics that provide insights into AD progression and outline how this knowledge may improve clinical trials.We used standard methods to identify nearly 600 publications using ADNI data from 2016 and 2017 (listed in Supplementary Material and searchable at http://adni.loni.usc.edu/news-publications/publications/).(1) Data-driven AD progression models supported multifactorial interactions rather than a linear cascade of events. (2) β-Amyloid (Aβ) deposition occurred concurrently with functional connectivity changes within the default mode network in preclinical subjects and was followed by specific and progressive disconnection of functional and anatomical networks. (3) Changes in functional connectivity, volumetric measures, regional hypometabolism, and cognition were detectable at subthreshold levels of Aβ deposition. 4. Tau positron emission tomography imaging studies detailed a specific temporal and spatial pattern of tau pathology dependent on prior Aβ deposition, and related to subsequent cognitive decline. 5. Clustering studies using a wide range of modalities consistently identified a "typical AD" subgroup and a second subgroup characterized by executive impairment and widespread cortical atrophy in preclinical and prodromal subjects. 6. Vascular pathology burden may act through both Aβ dependent and independent mechanisms to exacerbate AD progression. 7. The APOE ε4 allele interacted with cerebrovascular disease to impede Aβ clearance mechanisms. 8. Genetic approaches identified novel genetic risk factors involving a wide range of processes, and demonstrated shared genetic risk for AD and vascular disorders, as well as the temporal and regional pathological associations of established AD risk alleles. 9. Knowledge of early pathological changes guided the development of novel prognostic biomarkers for preclinical subjects. 10. Placebo populations of randomized controlled clinical trials had highly variable trajectories of cognitive change, underscoring the importance of subject selection and monitoring. 11. Selection criteria based on Aβ positivity, hippocampal volume, baseline cognitive/functional measures, and APOE ε4 status in combination with improved cognitive outcome measures were projected to decrease clinical trial duration and cost. 12. Multiple concurrent therapies targeting vascular health and other AD pathology in addition to Aβ may be more effective than single therapies.ADNI publications from 2016 and 2017 supported the idea of AD as a multifactorial disease and provided insights into the complexities of AD disease progression. These findings guided the development of novel biomarkers and suggested that subject selection on the basis of multiple factors may lower AD clinical trial costs and duration. The use of multiple concurrent therapies in these trials may prove more effective in reversing AD disease progression.

  View details for DOI 10.1016/j.jalz.2018.08.005

  View details for Web of Science ID 000455493000011

  View details for PubMedID 30321505

• Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-An emerging role for gut microbiome ALZHEIMERS & DEMENTIA MahmoudianDehkordi, S., Arnold, M., Nho, K., Ahmad, S., Jia, W., Xie, G., Louie, G., Kueider-Paisley, A., Moseley, M., Thompson, J., Williams, L., Tenenbaum, J. D., Blach, C., Baillie, R., Han, X., Bhattacharyya, S., Toledo, J. B., Schafferer, S., Klein, S., Koal, T., Risacher, S. L., Kling, M., Motsinger-Reif, A., Rotroff, D. M., Jack, J., Hankemeier, T., Bennett, D. A., De Jager, P. L., Trojanowski, J. Q., Shaw, L. M., Weiner, M. W., Doraiswamy, P., van Duijn, C. M., Saykin, A. J., Kastenmueller, G., Kaddurah-Daouk, R., Aisen, P., Weiner, M., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Morris, J., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Thal, L., Thal, L., Buckholtz, N., Snyder, P. J., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rogers, J., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hergesheimen, L., Hayes, J., Finley, S., Jack, C. R., Householder, E., Friedl, K., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Porsteinsso, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Landau, S., Rosen, H., Behan, K., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Li, G., Wolday, S., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Yesavage, J. A., Furst, A. J., Alzheimers Dis Neuroimaging, Alzheimer Dis Metabolomics 2019; 15 (1): 76–92

  Abstract

  Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. Bile acids (BAs), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer's disease (AD).Serum levels of 15 primary and secondary BAs and their conjugated forms were measured in 1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 with late mild cognitive impairment, and 305 AD cases enrolled in the AD Neuroimaging Initiative. We assessed associations of BA profiles including selected ratios with diagnosis, cognition, and AD-related genetic variants, adjusting for confounders and multiple testing.In AD compared to cognitively normal older adults, we observed significantly lower serum concentrations of a primary BA (cholic acid [CA]) and increased levels of the bacterially produced, secondary BA, deoxycholic acid, and its glycine and taurine conjugated forms. An increased ratio of deoxycholic acid:CA, which reflects 7α-dehydroxylation of CA by gut bacteria, strongly associated with cognitive decline, a finding replicated in serum and brain samples in the Rush Religious Orders and Memory and Aging Project. Several genetic variants in immune response-related genes implicated in AD showed associations with BA profiles.We report for the first time an association between altered BA profile, genetic variants implicated in AD, and cognitive changes in disease using a large multicenter study. These findings warrant further investigation of gut dysbiosis and possible role of gut-liver-brain axis in the pathogenesis of AD.

  View details for PubMedID 30337151

• Cortical thickness atrophy in the transentorhinal cortex in mild cognitive impairment NEUROIMAGE-CLINICAL Kulason, S., Tward, D. J., Brown, T., Sicat, C. S., Liu, C., Ratnanather, J., Younes, L., Bakker, A., Gallagher, M., Albert, M., Miller, M. I., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Mackin, S., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., Alzheimers Dis Neuroimaging Initi 2019; 21: 101617

  Abstract

  This study examines the atrophy rates of subjects with mild cognitive impairment (MCI) compared to controls in four regions within the medial temporal lobe: the transentorhinal cortex (TEC), entorhinal cortex (ERC), hippocampus, and amygdala. These regions were manually segmented and then corrected for undesirable longitudinal variability via Large Deformation Diffeomorphic Metric Mapping (LDDMM) based longitudinal diffeomorphometry. Diffeomorphometry techniques were used to compare thickness measurements in the TEC with the ERC. There were more significant changes in thickness atrophy rate in the TEC than medial regions of the entorhinal cortex. Volume measures were also calculated for all four regions. Classifiers were constructed using linear discriminant analysis to demonstrate that average thickness and atrophy rate of TEC together was the most discriminating measure compared to the thickness and volume measures in the areas examined, in differentiating MCI from controls. These findings are consistent with autopsy findings demonstrating that initial neuronal changes are found in TEC before spreading more medially in the ERC and to other regions in the medial temporal lobe. These findings suggest that the TEC thickness could serve as a biomarker for Alzheimer's disease in the prodromal phase of the disease.

  View details for DOI 10.1016/j.nicl.2018.101617

  View details for Web of Science ID 000460337700030

  View details for PubMedID 30552075

• Prognosis of conversion of mild cognitive impairment to Alzheimer's dementia by voxel-wise Cox regression based on FDG PET data NEUROIMAGE-CLINICAL Soerensen, A., Blazhenets, G., Ruecker, G., Schiller, F., Meyer, P., Frings, L., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Mackin, S., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., Alzheimers Dis Neuroimaging Initi 2019; 21: 101637

  Abstract

  The value of 18F-fluorodeoxyglucose (FDG) PET for the prognosis of conversion from mild cognitive impairment (MCI) to Alzheimer's dementia (AD) is controversial. In the present work, the identification of cerebral metabolic patterns with significant prognostic value for conversion of MCI patients to AD is investigated with voxel-based Cox regression, which in contrast to common categorical comparisons also utilizes time information.FDG PET data of 544 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were randomly split into two equally-sized datasets (training and test). Within a median follow-up duration of 47 months (95% CI: 46-48 months) 181 patients developed AD. In the training dataset, voxel-wise Cox regressions were used to identify regions associated with conversion of MCI to AD. These were compared to regions identified by a classical group comparison (analysis of covariance (ANCOVA) with statistical parametric mapping (SPM) 8) between converters and non-converters (both adjusted for apolipoprotein E (APOE) genotype, mini-mental state examination (MMSE) score, age, sex and education). In the test dataset, normalized FDG uptake within significant brain regions from voxel-wise Cox- and ANCOVA analyses (Cox- and ANCOVA- regions of interest (ROI), respectively) and clinical variables APOE status, MMSE score and education were tested in different Cox models (adjusted for age, sex) including: (1) only clinical variables, (2) only normalized FDG uptake in ANCOVA-ROI, (3) only normalized FDG uptake from Cox-ROI, (4) clinical variables plus FDG uptake in ANCOVA-ROI, (5) clinical variables plus FDG uptake from Cox-ROI.Conversion-related regions with relative hypometabolism comprised parts of the temporo-parietal and posterior cingulate cortex/precuneus for voxel-wise ANCOVA, plus frontal regions for voxel-wise Cox regression (both p < .01, false discovery rate (FDR) corrected). The clinical-only model (1) and the models based on normalized FDG uptake from Cox-ROI only (2) and ANCOVA-ROI only (3) all significantly predicted conversion to AD (Wald Test (WT): p < .001). The clinical model (1) was significantly improved by adding imaging information in model (4) (Akaike information criterion (AIC) relative likelihood (RL) (1) vs (4): RL < 0.018). There were no significant differences between models (2) and (3), as well as (4) and (5).Voxel-wise Cox regression identifies conversion-related patterns of cerebral glucose metabolism, but is not superior to classical group contrasts in this regard. With imaging information from both FDG PET patterns, the prediction of conversion to AD was improved.

  View details for DOI 10.1016/j.nicl.2018.101637

  View details for Web of Science ID 000460337700050

  View details for PubMedID 30553760

• Sex Differences in the Neuropsychiatric Symptoms of Patients With Alzheimer's Disease AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS Tao, Y., Peters, M. E., Drye, L. T., Devanand, D. P., Mintzer, J. E., Pollock, B. G., Porsteinsson, A. P., Rosenberg, P. B., Schneider, L. S., Shade, D. M., Weintraub, D., Yesavage, J., Lyketsos, C. G., Munro, C. A., CitAD Res Grp 2018; 33 (7): 450–57

  Abstract

  The aim of this study was to describe sex differences in neuropsychiatric symptoms (NPSs) in patients with Alzheimer's disease (AD). Baseline scores on the Cohen-Mansfield Agitation Inventory, Neurobehavioral Rating Scale-Agitation subscale, and the Neuropsychiatric Inventory from patients with AD enrolled in a multicenter trial of citalopram for the treatment of agitation were analyzed. We found not only that patients with AD having agitation were likely to exhibit many other NPSs but also that the women in this study were more likely to exhibit a broader range of NPS than were the men. These results suggest greater heterogeneity in the clinical presentation of women compared to men, and thus in the potential targets for treatment in these patients. Further characterization of sex differences in NPS can inform future efforts aimed at establishing subtypes of patients for whom various treatment approaches will be most appropriate.

  View details for PubMedID 29969907

• Effect of Repetitive Transcranial Magnetic Stimulation on Treatment-Resistant Major Depression in US Veterans A Randomized Clinical Trial JAMA PSYCHIATRY Yesavage, J. A., Fairchild, J., Mi, Z., Biswas, K., Davis-Karim, A., Phibbs, C. S., Forman, S. D., Thase, M., Williams, L. M., Etkin, A., O'Hara, R., Georgette, G., Beale, T., Huang, G. D., Noda, A., George, M. S., VA Cooperative Studies Program Stu 2018; 75 (9): 884–93

  Abstract

  Treatment-resistant major depression (TRMD) in veterans is a major clinical challenge given the high risk for suicidality in these patients. Repetitive transcranial magnetic stimulation (rTMS) offers the potential for a novel treatment modality for these veterans.To determine the efficacy of rTMS in the treatment of TRMD in veterans.A double-blind, sham-controlled randomized clinical trial was conducted from September 1, 2012, to December 31, 2016, in 9 Veterans Affairs medical centers. A total of 164 veterans with TRD participated.Participants were randomized to either left prefrontal rTMS treatment (10 Hz, 120% motor threshold, 4000 pulses/session) or to sham (control) rTMS treatment for up to 30 treatment sessions.The primary dependent measure of the intention-to-treat analysis was remission rate (Hamilton Rating Scale for Depression score ≤10, indicating that depression is in remission and not a clinically significant burden), and secondary analyses were conducted on other indices of posttraumatic stress disorder, depression, hopelessness, suicidality, and quality of life.The 164 participants had a mean (SD) age of 55.2 (12.4) years, 132 (80.5%) were men, and 126 (76.8%) were of white race. Of these, 81 were randomized to receive active rTMS and 83 to receive sham. For the primary analysis of remission, there was no significant effect of treatment (odds ratio, 1.16; 95% CI, 0.59-2.26; P = .67). At the end of the acute treatment phase, 33 of 81 (40.7%) of those in the active treatment group achieved remission of depressive symptoms compared with 31 of 83 (37.4%) of those in the sham treatment group. Overall, 64 of 164 (39.0%) of the participants achieved remission.A total of 39.0% of the veterans who participated in this trial experienced clinically significant improvement resulting in remission of depressive symptoms; however, there was no evidence of difference in remission rates between the active and sham treatments. These findings may reflect the importance of close clinical surveillance, rigorous monitoring of concomitant medication, and regular interaction with clinic staff in bringing about significant improvement in this treatment-resistant population.ClinicalTrials.gov Identifier: NCT01191333.

  View details for PubMedID 29955803

• REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION FOR IMPROVING COGNITION IN VETERANS WITH TBI: RESULTS FROM PILOT CLINICAL TRIAL Adamson, M., Siddiqi, S., Swaminath, G., Wu, L., Mcnerney, W., Darcy, V., Noda, A., Hernandez, B., Furst, A., Toll, R., Yutsis, M., Yochim, B., Clark, D., Etkin, A., Harris, O., Yesavage, J. MARY ANN LIEBERT, INC. 2018: A238

  View details for Web of Science ID 000441527400638

• F-18-florbetapir Positron Emission Tomography-determined Cerebral -Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery ANESTHESIOLOGY Klinger, R. Y., James, O. G., Borges-Neto, S., Bisanar, T., Li, Y., Qi, W., Berger, M., Terrando, N., Newman, M. F., Doraiswamy, P., Mathew, J. P., Alzheimers Dis Neuroimaging, NORG 2018; 128 (4): 728–44

  Abstract

  Amyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively.Amyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9). The association of 6-week amyloid deposition with cognitive dysfunction was assessed by multivariable regression, accounting for age, years of education, and baseline cognition. Differences between the surgical cohort with cognitive deficit and the Alzheimer's Disease Neuroimaging Initiative cohorts (normal and early/late mild cognitive impairment) was assessed, adjusting for age, education, and apolipoprotein E4 genotype.The authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) at 6 weeks postoperatively (median standard uptake value ratio [interquartile range]: cognitive dysfunction 0.92 [0.89 to 1.07] vs. 0.98 [0.93 to 1.05]; P = 0.455). In post hoc analyses, global cortical amyloid was also not associated with cognitive dysfunction at 1 or 3 yr postoperatively. Amyloid deposition at 6 weeks in the surgical cohort was not different from that in normal Alzheimer's Disease Neuroimaging Initiative subjects, but increased over 1 yr in many areas at a rate greater than in controls.In this study, postoperative cognitive dysfunction was not associated with 6-week cortical amyloid deposition. The relationship between cognitive dysfunction and regional amyloid burden and the rate of postoperative amyloid deposition merit further investigation.

  View details for PubMedID 29389750

  View details for PubMedCentralID PMC5849499

• Intrinsic functional connectivity predicts remission on antidepressants: a randomized controlled trial to identify clinically applicable imaging biomarkers TRANSLATIONAL PSYCHIATRY Goldstein-Piekarski, A. N., Staveland, B. R., Ball, T. M., Yesavage, J., Korgaonkar, M. S., Williams, L. M. 2018; 8: 57

  Abstract

  Default mode network (DMN) dysfunction (particularly within the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC)) has been implicated in major depressive disorder (MDD); however, its contribution to treatment outcome has not been clearly established. Here we tested the role of DMN functional connectivity as a general and differential biomarker for predicting treatment outcomes in a large, unmedicated adult sample with MDD. Seventy-five MDD outpatients completed fMRI scans before and 8 weeks after randomization to escitalopram, sertraline, or venlafaxine-XR. A whole-brain voxel-wise t-test identified profiles of pretreatment intrinsic functional connectivity that distinguished patients who were subsequently classified as remitters or non-remitters at follow-up. Connectivity was seeded in the PCC, an important node of the DMN. We further characterized differences between remitters, non-remitters, and 31 healthy controls and characterized changes pretreatment to posttreatment. Remitters were distinguished from non-remitters by relatively intact connectivity between the PCC and ACC/mPFC, not distinguishable from healthy controls, while non-remitters showed relative hypo-connectivity. In validation analyses, we demonstrate that PCC-ACC/mPFC connectivity predicts remission status with >80% cross-validated accuracy. In analyses testing whether intrinsic connectivity differentially relates to outcomes for a specific type of antidepressant, interaction models did not survive the corrected threshold. Our findings demonstrate that the overall capacity to remit on commonly used antidepressants may depend on intact organization of intrinsic functional connectivity between PCC and ACC/mPFC prior to treatment. The findings highlight the potential utility of functional scans for advancing a more precise approach to tailoring antidepressant treatment choices.

  View details for PubMedID 29507282

• Integration of neural and epigenetic contributions to posttraumatic stress symptoms: The role of hippocampal volume and glucocorticoid receptor gene methylation PLOS ONE McNerney, M., Sheng, T., Nechvatal, J. M., Lee, A. G., Lyons, D. M., Soman, S., Liao, C., O'Hara, R., Hallmayer, J., Taylor, J., Ashford, J., Yesavage, J., Adamson, M. M. 2018; 13 (2): e0192222

  Abstract

  Many Veterans exposed to physical and psychological trauma experience symptoms of posttraumatic stress disorder (PTSD). As the etiology of PTSD symptoms is complex, a better understanding of the underlying biological mechanisms may improve preventative care and treatment for PTSD. Recent findings from the fields of neuroimaging and epigenetics offer important insights into the potential brain structures and biochemical pathways of modified gene expression associated with PTSD. We combined neuroimaging and epigenetic measures to assess current PTSD symptoms by measuring overall hippocampal volume and methylation of the glucocorticoid receptor (GR) gene (promoter region). Multiple regression analyses indicated that the hippocampal volume/GR methylation interaction was a predictor of PTSD symptoms. Our findings suggest that neuroimaging and epigenetic measures contribute interactively to PTSD symptoms. Incorporation of these metrics may aid in the identification and treatment of PTSD patients.

  View details for DOI 10.1371/journal.pone.0192222

  View details for Web of Science ID 000424325300060

  View details for PubMedID 29415058

  View details for PubMedCentralID PMC5802910

• MULTIPLE INCOMPLETE VIEWS CLUSTERING VIA NON-NEGATIVE MATRIX FACTORIZATION WITH ITS APPLICATION IN ALZHEIMER'S DISEASE ANALYSIS Liu, K., Wang, H., Risacher, S., Saykin, A., Shen, L., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Carlsson, C. M., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Potkin, S. G., Preda, A., Nguyen, D., Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshal, G., Sabbagh, M. N., Jacobson, S. A., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Mackin, S., Aisen, P., Raman, R., Mackin, S., Weiner, M., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Feber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., ADNI, IEEE IEEE. 2018: 1402–5

  View details for Web of Science ID 000455045600323

• INTEGRATING SEMI-SUPERVISED LABEL PROPAGATION AND RANDOM FORESTS FOR MULTI-ATLAS BASED HIPPOCAMPUS SEGMENTATION Zheng, Q., Fan, Y., Weiner, M. W., Aisen, P., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Lilly, E., Logovinsky, V., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Thal, L., Khachaturian, Z., Thal, L., Buckholtz, N., Weiner, M. W., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Khachaturian, Z., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Carlsson, C. M., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Potkin, S. G., Preda, A., Nguyen, D., Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Mackin, S., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Koeppe, R. A., Landau, S., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., Alzheimer's Dis Neuroimaging, IEEE IEEE. 2018: 154–57

  Abstract

  A novel multi-atlas based image segmentation method is proposed by integrating a semi-supervised label propagation method and a supervised random forests method in a pattern recognition based label fusion framework. The semi-supervised label propagation method takes into consideration local and global image appearance of images to be segmented and segments the images by propagating reliable segmentation results obtained by the supervised random forests method. Particularly, the random forests method is used to train a regression model based on image patches of atlas images for each voxel of the images to be segmented. The regression model is used to obtain reliable segmentation results to guide the label propagation for the segmentation. The proposed method has been compared with state-of-the-art multi-atlas based image segmentation methods for segmenting the hippocampus in MR images. The experiment results have demonstrated that our method obtained superior segmentation performance.

  View details for Web of Science ID 000455045600033

  View details for PubMedID 30079126

  View details for PubMedCentralID PMC6070300

• PREDICTING PROGRESSIONS OF COGNITIVE OUTCOMES VIA HIGH-ORDER MULTI-MODAL MULTI-TASK FEATURE LEARNING Lu, L., Wang, H., Yao, X., Risacher, S., Saykin, A., Shen, L., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Logovinsky, V., Lilly, E., Green, R. C., Montine, T., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarc, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Khachaturian, Z., Buckholtz, N., Snyder, P. J., Potter, W., Paul, S., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silbert, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Morris, J. C., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulyss, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyc, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltze, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Weiner, M. W., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowki, J. Q., Neylan, T., Grafman, J., Green, R. C., Montine, T., Weiner, M., Petersen, R., Aisen, P., Jimenez, G., Donohue, M., Gessert, D., Salazar, J., Cabrera, Y., Walter, S., Hergesheimen, L., Neylan, T., Hayes, J., Finley, S., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Weiner, M. W., Friedl, K., Schneider, L. S., Pawluczyk, S., Becerra, M., Brewer, J., Vanderswag, H., Stern, Y., Honig, L. S., Bell, K. L., Fleischman, D., Arfanakis, K., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Doraiswamy, P., Petrella, J. R., James, O., Porsteinsson, A. P., Goldstein, B., Martin, K. S., Potkin, S. G., Preda, A., Nguyen, D., Mintzer, J., Massoglia, D., Brawman-Mintzer, O., Sadowsky, C., Martinez, W., Villena, T., Jagust, W., Landau, S., Rosen, H., Perry, D., Turner, R., Behan, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Obisesan, T. O., Wolday, S., Allard, J., Johnson, S. C., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., Furst, A. J., Chao, S., Relkin, N., Chiang, G., Ravdin, L., Mackin, S., Aisen, P., Raman, R., Mackin, S., Weiner, M., Aisen, P., Raman, R., Jack, C. R., Landau, S., Saykin, A. J., Toga, A. W., DeCarli, C., Koeppe, R. A., Green, R. C., Drake, E., Weiner, M., Aisen, P., Raman, R., Donohue, M., Jimenez, G., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Shaffer, E., Mackin, S., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Kantarci, K., Ward, C., Reyes, D., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Faber, K. M., Nho, K., Nudelman, K. N., Mackin, S., Rosen, H., Nelson, C., Bickford, D., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Butters, M., Zmuda, M., Lopez, O. L., Oakley, M., Simpson, D. M., ADNI, IEEE IEEE. 2018: 545–48

  View details for Web of Science ID 000455045600124

• APOE genotype and early beta-amyloid accumulation in older adults without dementia NEUROLOGY Lim, Y., Mormino, E. C., Alzheimer's Dis Neuroimaging Initi 2017; 89 (10): 1028–34

  Abstract

  To clarify associations between APOE ε4 allele and age on longitudinal rates of β-amyloid (Aβ) accumulation within Aβ+ and Aβ- older individuals without dementia.We analyzed 595 older adults without dementia classified cross-sectionally as Aβ- (n = 325) and Aβ+ (n = 270) using longitudinal florbetapir PET. The influence of age and APOE genotype on longitudinal accumulation of Aβ was examined with linear mixed models.APOE ε4 and older age were associated with higher risk of being classified as Aβ+ at baseline. The annual rate of Aβ accumulation was significantly greater than zero for Aβ- ε3 (0.0021 ± 0.0007 standardized uptake value ratio [SUVR] units) and Aβ- ε4 (0.0044 ± 0.0010 SUVR units), as well as Aβ+ ε3 (0.0141 ± 0.0019 SUVR units) and Aβ+ ε4 (0.0126 ± 0.0018 SUVR units). Aβ accumulation was significantly faster in Aβ- ε4 compared to Aβ- ε3 and Aβ- ε2. Rates of Aβ accumulation did not differ significantly between Aβ+ APOE groups. Older age was associated with higher rates of Aβ accumulation in the Aβ- group.APOE ε4 carriage and older age were predictors of longitudinal Aβ accumulation within the Aβ- group but not the Aβ+ group. APOE ε2 carriage was protective against longitudinal Aβ accumulation within the Aβ- group. APOE genotype in conjunction with chronologic age may aid in participant selection for primary prevention trials aimed at halting Aβ accumulation before abnormal levels are reached.

  View details for PubMedID 28794245

  View details for PubMedCentralID PMC5589795

• Repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression (TRMD) Veteran patients: study protocol for a randomized controlled trial TRIALS Mi, Z., Biswas, K., Fairchild, J., Davis-Karim, A., Phibbs, C. S., Forman, S. D., Thase, M., Georgette, G., Beale, T., Pittman, D., McNerney, M., Rosen, A., Huang, G. D., George, M., Noda, A., Yesavage, J. A. 2017; 18: 409

  Abstract

  Evaluation of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression (TRMD) in Veterans offers unique clinical trial challenges. Here we describe a randomized, double-blinded, intent-to-treat, two-arm, superiority parallel design, a multicenter study funded by the Cooperative Studies Program (CSP No. 556) of the US Department of Veterans Affairs.We recruited medical providers with clinical expertise in treating TRMD at nine Veterans Affairs (VA) medical centers as the trial local investigators. We plan to enroll 360 Veterans diagnosed with TRMD at the nine VA medical centers over a 3-year period. We will randomize participants into a double-blinded clinical trial to left prefrontal rTMS treatment or to sham (control) rTMS treatment (180 participants each group) for up to 30 treatment sessions. All participants will meet Diagnostic and statistical manual of mental disorders, 4 th edition (DSM-IV) criteria for major depression and will have failed at least two prior pharmacological interventions. In contrast with other rTMS clinical trials, we will not exclude Veterans with posttraumatic stress disorder (PTSD) or history of substance abuse and we will obtain detailed history regarding these disorders. Furthermore, we will maintain participants on stable anti-depressant medication throughout the trial. We will evaluate all participants on a wide variety of potential predictors of treatment response including cognitive, psychological and functional parameters.The primary dependent measure will be remission rate (Hamilton Rating Scale for Depression (HRSD24) ≤ 10), and secondary analyses will be conducted on other indices. Comparisons between the rTMS and the sham groups will be made at the end of the acute treatment phase to test the primary hypothesis. The unique challenges to performing such a large technically challenging clinical trial with Veterans and potential avenues for improvement of the design in future trials will be described.ClinicalTrials.gov, NCT01191333 . Registered on 26 August 2010. This report is based on the protocol version 4.6 amended in February 2016. All items from the World Health Organization Trial Registration Data Set are listed in Appendix A.

  View details for PubMedID 28865495

• Clustering by Salience Network Activation to Emotional Faces Identifies a Transdiagnostic Subtype that is Associated with Specific Interoceptive Related Symptoms Goldstein-Piekarski, A., Ball, T., Samara, Z., Yesavage, J., Schatzberg, A., Korgaonkar, M., Williams, L. ELSEVIER SCIENCE INC. 2017: S133–S134

  View details for DOI 10.1016/j.biopsych.2017.02.341

  View details for Web of Science ID 000400348700327

• Resting-State Functional Connectivity Dysfunction of the Ventral Striatum in Anhedonia as a Transdiagnostic Process Samara, Z., Goldstein-Piekarski, A., Suppes, T., Yesavage, J., Williams, L. ELSEVIER SCIENCE INC. 2017: S192–S193

  View details for DOI 10.1016/j.biopsych.2017.02.956

  View details for Web of Science ID 000400348700469

• Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative FRONTIERS IN AGING NEUROSCIENCE Russo, M. J., Campos, J., Vazquez, S., Sevlever, G., Allegri, R. F., Alzheimer Dis Neuroimaging Initiat 2017; 9: 46

  Abstract

  Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ2 = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI.

  View details for PubMedID 28344552

• Susceptibility-Based Neuroimaging: Standard Methods, Clinical Applications, and Future Directions. Current radiology reports Soman, S., Bregni, J. A., Bilgic, B., Nemec, U., Fan, A., Liu, Z., Barry, R. L., Du, J., Main, K., Yesavage, J., Adamson, M. M., Moseley, M., Wang, Y. 2017; 5 (3)

  Abstract

  The evaluation of neuropathologies using MRI methods that leverage tissue susceptibility have become standard practice, especially to detect blood products or mineralization. Additionally, emerging MRI techniques have the ability to provide new information based on tissue susceptibility properties in a robust and quantitative manner. This paper discusses these advanced susceptibility imaging techniques and their clinical applications.

  View details for DOI 10.1007/s40134-017-0204-1

  View details for PubMedID 28695062

• DTI measures identify mild and moderate TBI cases among patients with complex health problems: A receiver operating characteristic analysis of US veterans NEUROIMAGE-CLINICAL Main, K. L., Soman, S., Pestilli, F., Furst, A., Noda, A., Hernandez, B., Kong, J., Cheng, J., Fairchild, J. K., Taylor, J., Yesavage, J., Ashford, J., Kraemer, H., Adamson, M. M. 2017; 16: 1–16

  Abstract

  Standard MRI methods are often inadequate for identifying mild traumatic brain injury (TBI). Advances in diffusion tensor imaging now provide potential biomarkers of TBI among white matter fascicles (tracts). However, it is still unclear which tracts are most pertinent to TBI diagnosis. This study ranked fiber tracts on their ability to discriminate patients with and without TBI. We acquired diffusion tensor imaging data from military veterans admitted to a polytrauma clinic (Overall n = 109; Age: M = 47.2, SD = 11.3; Male: 88%; TBI: 67%). TBI diagnosis was based on self-report and neurological examination. Fiber tractography analysis produced 20 fiber tracts per patient. Each tract yielded four clinically relevant measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity). We applied receiver operating characteristic (ROC) analyses to identify the most diagnostic tract for each measure. The analyses produced an optimal cutpoint for each tract. We then used kappa coefficients to rate the agreement of each cutpoint with the neurologist's diagnosis. The tract with the highest kappa was most diagnostic. As a check on the ROC results, we performed a stepwise logistic regression on each measure using all 20 tracts as predictors. We also bootstrapped the ROC analyses to compute the 95% confidence intervals for sensitivity, specificity, and the highest kappa coefficients. The ROC analyses identified two fiber tracts as most diagnostic of TBI: the left cingulum (LCG) and the left inferior fronto-occipital fasciculus (LIF). Like ROC, logistic regression identified LCG as most predictive for the FA measure but identified the right anterior thalamic tract (RAT) for the MD, RD, and AD measures. These findings are potentially relevant to the development of TBI biomarkers. Our methods also demonstrate how ROC analysis may be used to identify clinically relevant variables in the TBI population.

  View details for PubMedID 28725550

• Altered Microstructural Caudate Integrity in Posttraumatic Stress Disorder but Not Traumatic Brain Injury. PloS one Waltzman, D., Soman, S., Hantke, N. C., Fairchild, J. K., Kinoshita, L. M., Wintermark, M., Ashford, J. W., Yesavage, J., Williams, L., Adamson, M. M., Furst, A. J. 2017; 12 (1)

  Abstract

  Given the high prevalence and comorbidity of combat-related PTSD and TBI in Veterans, it is often difficult to disentangle the contributions of each disorder. Examining these pathologies separately may help to understand the neurobiological basis of memory impairment in PTSD and TBI independently of each other. Thus, we investigated whether a) PTSD and TBI are characterized by subcortical structural abnormalities by examining diffusion tensor imaging (DTI) metrics and volume and b) if these abnormalities were specific to PTSD versus TBI.We investigated whether individuals with PTSD or TBI display subcortical structural abnormalities in memory regions by examining DTI metrics and volume of the hippocampus and caudate in three groups of Veterans: Veterans with PTSD, Veterans with TBI, and Veterans with neither PTSD nor TBI (Veteran controls).While our results demonstrated no macrostructural differences among the groups in these regions, there were significant alterations in microstructural DTI indices in the caudate for the PTSD group but not the TBI group compared to Veteran controls.The result of increased mean, radial, and axial diffusivity, and decreased fractional anisotropy in the caudate in absence of significant volume atrophy in the PTSD group suggests the presence of subtle abnormalities evident only at a microstructural level. The caudate is thought to play a role in the physiopathology of PTSD, and the habit-like behavioral features of the disorder could be due to striatal-dependent habit learning mechanisms. Thus, DTI appears to be a vital tool to investigate subcortical pathology, greatly enhancing the ability to detect subtle brain changes in complex disorders.

  View details for DOI 10.1371/journal.pone.0170564

  View details for PubMedID 28114393

  View details for PubMedCentralID PMC5256941

• Exploratory Clustering for Patient Subpopulation Discovery INFORMATICS FOR HEALTH: CONNECTED CITIZEN-LED WELLNESS AND POPULATION HEALTH Gamberger, D., Zenko, B., Lavrac, N., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M., Potter, W., Snyder, P., Logovinsky, V., Montine, T., Jimenez, G., Donohue, M., Gessert, D., Harless, K., Salazar, J., Cabrera, Y., Walter, S., Hergesheimer, L., Harvey, D., Donohue, M., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Cairns, N. J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Buckholtz, N., Albert, M., Frank, R., Hsiao, J., Quinn, J., Silber, L. C., Lind, B., Kaye, J. A., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Becerra, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Ziolkowski, J., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Villanueva-Meyer, J., Pavlik, V., Pacini, N., Lamb, A., Kass, J. S., Doody, R. S., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Yeh, R., Ances, B., Winkfield, D., Carroll, M., Oliver, A., Creech, M. L., Mintun, M. A., Schneider, S., Marson, D., Geldmacher, D., Love, M., Griffith, R., Clark, D., Brockington, J., Grossman, H., Mitsis, E., Shah, R. C., Lamar, M., Samuels, P., Duara, R., Greig-Custo, M. T., Rodriguez, R., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M. O., Singleton-Garvin, J., Ulysse, A., Gaikwad, M., Doraiswamy, P., Petrella, J. R., James, O., Borges-Neto, S., Wong, T. Z., Coleman, E., Karlawish, J. H., Wolk, D. A., Vaishnavi, S., Clark, C. M., Arnold, S. E., Smith, C. D., Jicha, G., Hardy, P., El Khouli, R., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Martin, K., Kowalksi, N., Keltz, M., Goldstein, B. S., Makino, K. M., Ismail, M., Brand, C., Thai, G., Pierce, A., Yanez, B., Sosa, E., Witbracht, M., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Woo, E., Silverman, D. S., Teng, E., Kremen, S., Apostolova, L., Tingus, K., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Poki-Walker, K., Farlow, M. R., Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., van Dyck, C. H., Carson, R. E., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Heyn, C., Hsiung, G., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Pavlosky, W., Rachinsky, I., Drost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C., Johnson, N., Sadowsky, C., Villena, T., Turner, R., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G. A., Yesavage, J., Taylor, J. L., Chao, S., Lane, B., Rosen, A., Tinklenberg, J., Zamrini, E., Belden, C. M., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P., Obisesan, T. O., Oyonumo, N. E., Allard, J., Ogunlana, O., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Tariot, P., Burke, A., Hetelle, J., DeMarco, K., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Tarawneh, R., Zimmerman, E. A., Celmins, D., Hart, D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Yang, M., Mintz, A., Ott, B. R., Tremont, G., Daiello, L. A., Bodge, C., Salloway, S., Malloy, P., Correia, S., Lee, A., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Miller, D. D., Smith, K., Koleva, H., Nam, K., Shim, H., Schultz, S. K., Relkin, N., Chiang, G., Lin, M., Ravdin, L., Smith, A., Leach, C., Raj, B., Fargher, K., Neylan, T., Grafman, J., Hayes, J., Finley, S., Landau, S., Householder, E., Lee, V., Korecka, M., Figurski, M., Friedl, K., Fleischman, D., Arfanakis, K., Varon, D., Preda, A., Nguyen, D., Massoglia, D., Brawman-Mintzer, O., Martinez, W., Jagust, W., Landau, S., Rosen, H., Behan, K., Sabbagh, M. N., Jacobson, S. A., Sirrel, S. A., Wolday, S., Fruehling, J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Furst, A. J., Mackin, S., Raman, R., Drake, E., Donohue, M., Shaffer, E., Nelson, C., Bickford, D., Butters, M., Zmuda, M., Reyes, D., Nudelman, K. N., Au, Y., Scherer, K., Catalinotto, D., Stark, S., Ong, E., Fernandez, D., Alzheimer's Dis Neuroimaging Init, Randell, R., Cornet, R., McCowan, C., Peek, N., Scott, P. J. 2017; 235: 101–5

  View details for DOI 10.3233/978-1-61499-753-5-101

  View details for Web of Science ID 000458298900021

• Resting-State Functional Connectivity Dysfunction in Anhedonia as a Transdiagnostic Process: An RDoC Investigation Samara, Z., Goldstein-Piekarski, A. N., Suppes, T., Yesavage, J., Williams, L. NATURE PUBLISHING GROUP. 2016: S503

  View details for Web of Science ID 000440366400073

• R- and S-citalopram concentrations have differential effects on neuropsychiatric scores in elders with dementia and agitation. British journal of clinical pharmacology Ho, T., Pollock, B. G., Mulsant, B. H., Schantz, O., Devanand, D. P., Mintzer, J. E., Porsteinsson, A. P., Schneider, L. S., Weintraub, D., Yesavage, J., Drye, L. T., Munro, C. A., Shade, D. M., Lyketsos, C., Bies, R. 2016; 82 (3): 784-792

  Abstract

  The aim was to determine the relationship between (R) and (S)-citalopram enantiomer exposure (AUC(0,24 h)) and therapeutic response in agitated individuals greater than 60 years old with Alzheimer's dementia (AD).Citalopram enantiomer exposures (AUC(0,24 h)) derived from an established population pharmacokinetic analysis were utilized to explore the relationship between (R)- and (S)-citalopram area under the curve (AUC(0,24 )) and Mini-Mental State Examination (MMSE), Neurobehavioural Rating Scale-Agitation Subscale (NBRS-A), modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC) and Neuropsychiatric Inventory Agitation subscale (NPIA) scores. Time dependent changes in these scores (disease progression) were accounted for prior to exploring the exposure effect relationship for each enantiomer. These relationships were evaluated using a non-linear-mixed effects modelling approach as implemented in nonmem v7.3.(S)-AUC(0,24 h) and (R)-AUC(0,24 h) each contributed to improvement in NBRS-A scores (k3(R) -0.502; k4(S) -0.712) as did time in treatment. However, increasing (R)-AUC(0,24 h) decreased the probability of patient response (maximum Δ -0.182%/AUC(0,24 h)) based on the CGIC while (S)-AUC(0,24 h) improved the probability of response (maximum Δ 0.112%/AUC(0,24 h)). (R)-AUC(0,24 h) was also associated with worsening in MMSE scores (-0.5 points).Our results suggest that citalopram enantiomers contributed differentially to treatment outcomes. (R)-citalopram accounted for a greater proportion of the adverse consequences associated with racemic citalopram treatment in patients with AD including a decreased probability of treatment response as measured by the CGIC and a reduction in MMSE scores. The S-enantiomer was associated with increased probability of response based on the CGIC.

  View details for DOI 10.1111/bcp.12997

  View details for PubMedID 27145364

• Principal components analysis of agitation outcomes in Alzheimer's disease JOURNAL OF PSYCHIATRIC RESEARCH Yesavage, J. A., Taylor, J. L., Friedman, L., Rosenberg, P. B., Lazzeroni, L. C., Leoutsakos, J. S., Kinoshita, L. M., Perlow, M. J., Munro, C. A., Devanand, D. P., Drye, L. T., Mintzer, J. E., Pollock, B. G., Porsteinsson, A. P., Schneider, L. S., Shade, D. M., Weintraub, D., Lyketsos, C. G., Noda, A. 2016; 79: 4-7

  Abstract

  We developed a composite measure of agitation as a secondary outcome of change over time in the Citalopram for Agitation in Alzheimer's disease study (CitAD). CitAD demonstrated a positive effect of citalopram on agitation on the Neurobehavioral Rating Scale agitation subscale (NBRS-A). CitAD included additional agitation measures such as the Cohen-Mansfield Agitation Inventory and the Neuropsychiatric Inventory.We performed principal components analyses on change in individual item of these scales for the same, original CitAD subjects.The first principal component accounted for 12.6% of the observed variance and was composed of items that appear to reflect agitation. The effect size for citalopram calculated using this component was 0.53 (95% CI 0.22-0.83) versus 0.32 for the NBRS-A (95% CI 0.01-0.62).Results suggest that a composite measure of change in agitation might be more sensitive than change in a single primary agitation measure.

  View details for DOI 10.1016/j.jpsychires.2016.04.004

  View details for Web of Science ID 000378179000002

  View details for PubMedID 27115509

• Volume of Subclinical Microembolization Correlates to Long-term Cognitive Changes Following Carotid Revascularization Zhou, W., Hitchner, E., Bhat, J., Baughman, B., Soman, S., Wintermark, M., Rosen, A., Yesavage, J. MOSBY-ELSEVIER. 2016: 141S–142S

  View details for DOI 10.1016/j.jvs.2016.03.245

  View details for Web of Science ID 000376230600226

• Effects of Citalopram on Neuropsychiatric Symptoms in Alzheimer's Dementia: Evidence From the CitAD Study AMERICAN JOURNAL OF PSYCHIATRY Leonpacher, A. K., Peters, M. E., Drye, L. T., Makino, K. M., Newell, J. A., Devanand, D. P., Frangakis, C., Munro, C. A., Mintzer, J. E., Pollock, B. G., Rosenberg, P. B., Schneider, L. S., Shade, D. M., Weintraub, D., Yesavage, J., Lyketsos, C. G., Porsteinsson, A. P. 2016; 173 (5): 473-480

  Abstract

  Citalopram has been shown to improve agitation in patients with Alzheimer's disease. The authors evaluated whether other neuropsychiatric symptoms improve with citalopram treatment compared with placebo.In this planned secondary analysis of the Citalopram for Agitation in Alzheimer's Disease study, the authors evaluated the effect of citalopram on the 12 neuropsychiatric symptom domains assessed by the Neuropsychiatric Inventory (NPI). They compared caregiver-reported NPI scores at week 9 in patients receiving citalopram (30 mg/day) or placebo with regard to both the presence or absence of individual neuropsychiatric symptoms and individual domain scores (reflecting severity) in participants who had symptoms at week 9.At week 9, participants treated with citalopram were significantly less likely to be reported as showing delusions (odds ratio=0.40), anxiety (odds ratio=0.43), and irritability/lability (odds ratio=0.38). A comparison of median scores of participants with symptoms present at week 9 showed significant differences favoring citalopram for hallucinations and favoring placebo for sleep/nighttime behavior disorders.While dosage constraints must be considered because of citalopram's adverse effect profile, this agent's overall therapeutic effects in patients with Alzheimer's disease and agitation, in addition to efficacy for agitation/aggression, included reductions in the frequency of irritability, anxiety, and delusions; among patients who had these symptoms at week 9, they included a reduction in the severity of hallucinations but an increase in the severity of sleep/nighttime behavior disorders.

  View details for DOI 10.1176/appi.ajp.2016.15020248

  View details for Web of Science ID 000375291500010

  View details for PubMedID 27032628

• Heterogeneity of Treatment Response to Citalopram for Patients With Alzheimer's Disease With Aggression or Agitation: The CitAD Randomized Clinical Trial AMERICAN JOURNAL OF PSYCHIATRY Schneider, L. S., Frangakis, C., Drye, L. T., Devanand, D. P., Marano, C. M., Mintzer, J., Mulsant, B. H., Munro, C. A., Newell, J. A., Pawluczyk, S., Pelton, G., Pollock, B. G., Porsteinsson, A. P., Rabins, P. V., Rein, L., Rosenberg, P. B., Shade, D., Weintraub, D., Yesavage, J., Lyketsos, C. G. 2016; 173 (5): 465-472

  Abstract

  Pharmacological treatments for agitation and aggression in patients with Alzheimer's disease have shown limited efficacy. The authors assessed the heterogeneity of response to citalopram in the Citalopram for Agitation in Alzheimer Disease (CitAD) study to identify individuals who may be helped or harmed.In this double-blind parallel-group multicenter trial of 186 patients with Alzheimer's disease and clinically significant agitation, participants were randomly assigned to receive citalopram or placebo for 9 weeks, with the dosage titrated to 30 mg/day over the first 3 weeks. Five planned potential predictors of treatment outcome were assessed, along with six additional predictors. The authors then used a two-stage multivariate method to select the most likely predictors; grouped participants into 10 subgroups by their index scores; and estimated the citalopram treatment effect for each.Five covariates were likely predictors, and treatment effect was heterogeneous across the subgroups. Patients for whom citalopram was more effective were more likely to be outpatients, have the least cognitive impairment, have moderate agitation, and be within the middle age range (76-82 years). Patients for whom placebo was more effective were more likely to be in long-term care, have more severe cognitive impairment, have more severe agitation, and be treated with lorazepam.Considering several covariates together allowed the identification of responders. Those with moderate agitation and with lower levels of cognitive impairment were more likely to benefit from citalopram, and those with more severe agitation and greater cognitive impairment were at greater risk for adverse responses. Considering the dosages used and the association of citalopram with cardiac QT prolongation, use of this agent to treat agitation may be limited to a subgroup of people with dementia.

  View details for DOI 10.1176/appi.ajp.2015.15050648

  View details for Web of Science ID 000375291500009

  View details for PubMedID 26771737

• Negative Tuberculin Skin Test and Prediction of Reversion of QuantiFERON Interferon Gamma Release Assay in US Healthcare Workers INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Thanassi, W., Noda, A., Hernandez, B., Friedman, L., Dorman, S., Yesavage, J. 2016; 37 (4): 478-482

  Abstract

  QuantiFERON tuberculosis tests (QFT) reverted in (612) 77% of 1,094 low-risk healthcare workers (HCW) testing less than 1.16 IU/mL. Of HCW testing greater than 1.1 IU/mL, 33 (59%) of 56 with negative tuberculin skin tests (TST) reverted vs 8 (6%) of 125 with positive TSTs. Retesting low-risk QFT-positive and TST-negative HCW is prudent.

  View details for DOI 10.1017/ice.2015.324

  View details for Web of Science ID 000372796200018

• Developing a clinical translational neuroscience taxonomy for anxiety and mood disorder: protocol for the baseline-follow up Research domain criteria Anxiety and Depression ("RAD") project BMC PSYCHIATRY Williams, L. M., Goldstein-Piekarski, A. N., Chowdhry, N., Grisanzio, K. A., Haug, N. A., Samara, Z., Etkin, A., O'Hara, R., Schatzberg, A. F., Suppes, T., Yesavage, J. 2016; 16

  Abstract

  Understanding how brain circuit dysfunctions relate to specific symptoms offers promise for developing a brain-based taxonomy for classifying psychopathology, identifying targets for mechanistic studies and ultimately for guiding treatment choice. The goal of the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health is to accelerate the development of such neurobiological models of mental disorder independent of traditional diagnostic criteria. In our RDoC Anxiety and Depression ("RAD") project we focus trans-diagnostically on the spectrum of depression and anxiety psychopathology. Our aims are a) to use brain imaging to define cohesive dimensions defined by dysfunction of circuits involved in reactivity to and regulation of negatively valenced emotional stimulation and in cognitive control, b) to assess the relationships between these dimension and specific symptoms, behavioral performance and the real world capacity to function socially and at work and c) to assess the stability of brain-symptom-behavior-function relationships over time.Here we present the protocol for the "RAD" project, one of the first RDoC studies to use brain circuit functioning to define new dimensions of psychopathology. The RAD project follows baseline-follow up design. In line with RDoC principles we use a strategy for recruiting all clients who "walk through the door" of a large community mental health clinic as well as the surrounding community. The clinic attends to a broad spectrum of anxiety and mood-related symptoms. Participants are unmedicated and studied at baseline using a standardized battery of functional brain imaging, structural brain imaging and behavioral probes that assay constructs of threat reactivity, threat regulation and cognitive control. The battery also includes self-report measures of anxiety and mood symptoms, and social and occupational functioning. After baseline assessments, therapists in the clinic apply treatment planning as usual. Follow-up assessments are undertaken at 3 months, to establish the reliability of brain-based subgroups over time and to assess whether these subgroups predict real-world functional capacity over time. First enrollment was August 2013, and is ongoing.This project is designed to advance knowledge toward a neural circuit taxonomy for mental disorder. Data will be shared via the RDoC database for dissemination to the scientific community. The clinical translational neuroscience goals of the project are to develop brain-behavior profile reports for each individual participant and to refine these reports with therapist feedback. Reporting of results is expected from December 2016 onward.ClinicalTrials.gov Identifier: NCT02220309 . Registered: August 13, 2014.

  View details for DOI 10.1186/s12888-016-0771-3

  View details for Web of Science ID 000372738400001

  View details for PubMedCentralID PMC4793523

• Sedation mediates part of Citalopram's effect on agitation in Alzheimer's disease. Journal of psychiatric research Newell, J., Yesavage, J. A., Taylor, J. L., Kraemer, H. C., Munro, C. A., Friedman, L., Rosenberg, P. B., Madore, M., Chao, S. Z., Devanand, D. P., Drye, L. T., Mintzer, J. E., Pollock, B. G., Porsteinsson, A. P., Schneider, L. S., Shade, D. M., Weintraub, D., Lyketsos, C. G., Noda, A. 2016; 74: 17-21

  Abstract

  We found a benefit of citalopram for agitation in the Citalopram for Agitation in Alzheimer's Disease study (CitAD), and wondered if this was mediated by a sedative effect. CitAD was a randomized, placebo-controlled, double-blind, parallel group trial conducted at 8 academic centers in the United States and Canada from August 2009 to January 2013. One hundred sixty-two participants with probable Alzheimer's disease (AD) and clinically significant agitation were analyzed in this study. Participants received a psychosocial intervention and were randomized to receive either citalopram or placebo (approximately half assigned to each group). Participants were rated on the Neurobehavioral Rating Scale Agitation subscale and measures of sedation (i.e., fatigue and somnolence).Using the MacArthur Foundation procedures for documenting a mediator effect, we performed a secondary analysis examining whether sedation mediates the effect of treatment on agitation outcome.We found a statistically significant mediating effect of sedation on agitation outcomes, but the magnitude of the effect was small, only explaining 11% of the variance in agitation, with a significant, but modest effect size of 0.16 (95% CI: 0.08 to 0.22).The benefit of citalopram was partly due to sedation but largely due to other mechanisms of action.

  View details for DOI 10.1016/j.jpsychires.2015.12.005

  View details for PubMedID 26736036

  View details for PubMedCentralID PMC4744510

• Indirect Effects of Behavioral Treatment for Insomnia on Depression, Anxiety, Perceived Stress and Telomere Length Yesavage, J. A., Yessengaliyeva, E., Hernandez, B., Noda, A., Thompson, S., Lee, R., Posner, D. A., Lin, J., Neylan, T., Zeitzer, J., Friedman, L. ELSEVIER SCIENCE INC. 2016: S84–S85

  View details for DOI 10.1016/j.jagp.2016.01.081

  View details for Web of Science ID 000408541600072

• Citalopram for the Treatment of Agitation in Alzheimer Dementia: Genetic Influences. Journal of geriatric psychiatry and neurology Peters, M. E., Vaidya, V., Drye, L. T., Devanand, D. P., Mintzer, J. E., Pollock, B. G., Porsteinsson, A. P., Rosenberg, P. B., Schneider, L. S., Shade, D. M., Weintraub, D., Yesavage, J., Lyketsos, C. G., Avramopoulos, D. 2016; 29 (2): 59-64

  Abstract

  To assess potential genetic influences on citalopram treatment efficacy for agitation in individuals with Alzheimer dementia (AD). Six functional genetic variants were studied in the following genes: serotonin receptor 2A (HTR2A-T102C), serotonin receptor 2C (HTR2C-Cys23Ser), serotonin transporter (5HTT-LPR), brain-derived neurotropic factor (BDNF-Val66Met), apolipoprotein E (ε2, ε3, ε4 variants), and cytochrome P450 (CYP2C19). Treatment response by genotype was measured by (1) the agitation domain of the Neurobehavioral Rating Scale, (2) the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change scale (mADCS-CGIC), (3) the agitation domain of the Neuropsychiatric Inventory (NPI), and (4) the Cohen-Mansfield Agitation Inventory.We utilized data from the Citalopram for Agitation in Alzheimer's Disease (CitAD) database. CitAD was a 9-week randomized, double-blind, placebo-controlled multicenter clinical trial showing significant improvement in agitation and caregiver distress in patients treated with citalopram. Proportional odds logistic regression and mixed effects models were used to examine the above-mentioned outcome measures.Significant interactions were noted on the NPI agitation domain for HTR2A (likelihood ratio [LR] = 6.19, df = 2, P = .04) and the mADCS-CGIC for HTR2C (LR = 4.33, df = 2, P = .02) over 9 weeks.Treatment outcomes in CitAD showed modest, although statistically significant, influence of genetic variation at HTR2A and HTR2C loci. Future studies should continue to examine the interaction of known genetic variants with antidepressant treatment in patients with AD having agitation.

  View details for DOI 10.1177/0891988715601735

  View details for PubMedID 26303700

• A population pharmacokinetic model for R- and S-citalopram and desmethylcitalopram in Alzheimer's disease patients with agitation. Journal of pharmacokinetics and pharmacodynamics Akil, A., Bies, R. R., Pollock, B. G., Avramopoulos, D., Devanand, D. P., Mintzer, J. E., Porsteinsson, A. P., Schneider, L. S., Weintraub, D., Yesavage, J., Shade, D. M., Lyketsos, C. G. 2016; 43 (1): 99-109

  Abstract

  The citalopram for Alzheimer's disease trial evaluated citalopram for the management for agitation in Alzheimer's disease patients. Sparse data was available from this elderly patient population. A nonlinear mixed effects population pharmacokinetic modeling approach was used to describe the pharmacokinetics of R- and S-citalopram and their primary metabolite (desmethylcitalopram). A structural model with 4 compartments (one compartment/compound) with linear oral absorption and elimination described the data adequately. Overall, the model showed that clearance of the R-enantiomer was slower than the clearance of the S-enantiomer. Without accounting for any patient-specific covariates, the population estimate of the metabolic clearance of citalopram was 8.6 (R-citalopram) and 14 L/h (S-citalopram). The population estimate of the clearance of desmethylcitalopram was 23.8 (R-Dcit) and 38.5 L/h (S-Dcit). Several patient-specific covariates were found to have a significant effect on the pharmacokinetics of R,S-citalopram and desmethylcitalopram. A significant difference in the metabolic clearance of R-citalopram between males and females (13 vs 9.05 L/h) was identified in this analysis. Both R- and S-citalopram metabolic clearance decreased with age. Additionally, consistent with literature reports S-citalopram metabolic clearance increased with increasing body weight and was significantly influenced by CYPC19 genotype, with a difference of 5.8 L/h between extensive/rapid and intermediate/poor metabolizers. R,S-desmethylcitalopram clearance increased with increasing body weight. This model may allow for the opportunity to delineate the effect of R- and S-citalopram on pharmacodynamics outcomes related to the management of agitation in Alzheimer's disease.

  View details for DOI 10.1007/s10928-015-9457-6

  View details for PubMedID 26611790

  View details for PubMedCentralID PMC4720707

• Effects of Posttraumatic Stress Disorder and Metabolic Syndrome on Cognitive Aging in Veterans. Gerontologist Green, E., Fairchild, J. K., Kinoshita, L. M., Noda, A., Yesavage, J. 2016; 56 (1): 72-81

  Abstract

  With the influx of veterans entering older adulthood, it is increasingly important to understand risk factors for cognitive decline. Posttraumatic stress disorder (PTSD) and the metabolic syndrome (MetS) are highly prevalent in older veterans. Although both increase risk for cognitive decline and often co-occur, it is unclear how they may interact to negatively impact cognition. The aim of this cross-sectional study was to investigate associations among PTSD, MetS, and cognitive function in older veterans. We hypothesized that co-occurring PTSD and MetS would be associated with worse cognitive performance than seen in either illness alone.Participants completed cognitive testing to assess processing speed, verbal memory, and executive function. Data from 204 male veterans aged 55-89 were analyzed with the use of hierarchical multiple regression models.Veterans with MetS demonstrated poorer performance on tasks of executive function (response inhibition and cognitive set shifting) and immediate verbal memory regardless of PTSD status. There was an interaction between MetS and PTSD on delayed verbal memory, suggesting that the negative impact of MetS on verbal memory was only significant for veterans not classified as having PTSD.This is the first study to examine the impact of comorbid PTSD and MetS on cognition. The results suggest that MetS is associated with poorer verbal learning and executive functioning independent of PTSD. We discuss the necessity of monitoring cerebrovascular risk factors and providing early behavioral and/or pharmaceutical interventions to lessen the risk of cognitive decline in older age.

  View details for DOI 10.1093/geront/gnv040

  View details for PubMedID 26220415

• Ubiquity of Undiagnosed Sleep Disordered Breathing in Community-Dwelling Older Male Veterans. American journal of geriatric psychiatry Iqbal, N., Kinoshita, L. M., Noda, A., Friedman, L., Yesavage, J. A., Zeitzer, J. M. 2016; 24 (2): 170-173

  Abstract

  To determine the point prevalence of sleep disordered breathing (SDB) in a community-based sample of older male veterans and to determine if common markers of SDB apply to this population.Two hundred fourteen older male Veterans (age 55-89 years) were recruited for a study on post-traumatic stress disorder and cognitive decline. Questionnaires concerning anthropomorphic and psychological variables were obtained, as was an overnight polysomnographic examination of sleep.Only 13% of the participants lacked clinically meaningful SDB, whereas 33% had moderate SDB and 54% had severe SDB. Being overweight, self-reported snoring, and excessive daytime sleepiness all had good sensitivity (0.86-0.92) but very poor specificity (0.10-0.28) for the prediction of SDB.Undiagnosed SDB was more than threefold higher than expected in these community-dwelling older veterans. Traditional markers of SDB were not specific for predicting clinically relevant SDB.

  View details for DOI 10.1016/j.jagp.2015.08.004

  View details for PubMedID 26778348

• The influence of physical and mental health symptoms on Veterans' functional health status JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT Sheng, T., Fairchild, J. K., Kong, J. Y., Kinoshita, L. M., Cheng, J. J., Yesavage, J. A., Helmer, D. A., Reinhard, M. J., Ashford, J. W., Adamson, M. M. 2016; 53 (6): 781-795

  Abstract

  Veterans who have been deployed to combat often have complex medical histories including some combination of traumatic brain injury (TBI); mental health problems; and other chronic, medically unexplained symptoms (i.e., chronic multisymptom illness [CMI] clusters). How these multiple pathologies relate to functional health is unclear. In the current study, 120 Veterans (across multiple combat cohorts) underwent comprehensive clinical evaluations and completed self-report assessments of mental health symptoms (Patient Health Questionnaire-2 [PHQ-2], PTSD Checklist-Civilian Version [PCL-C]) and functional health (Veterans Rand 36-Item Health Survey). Canonical correlation and regression modeling using split-sample permutation tests revealed that the PHQ-2/PCL-C composite variable (among TBI severity and number of problematic CMI clusters) was the primary predictor of multiple functional health domains. Two subscales, Bodily Pain and General Health, were associated with multiple predictors (TBI, PHQ-2/PCL-C, and CMI; and PHQ-2/PCL-C and CMI, respectively), demonstrating the multifaceted nature of how distinct medical problems might uniquely and collectively impair aspects of functional health. Apart from these findings, however, TBI and CMI were not predictors of any other aspects of functional health. Taken together, our findings suggest that mental health problems might exert ubiquitous influence over multiple domains of functional health. Thus, screening of mental health problems and education and promotion of mental health resources can be important to the treatment and care of Veterans.

  View details for DOI 10.1682/JRRD.2015.07.0146

  View details for Web of Science ID 000393985100012

• The influence of physical and mental health symptoms on Veterans' functional health status. Journal of rehabilitation research and development Sheng, T., Fairchild, J. K., Kong, J. Y., Kinoshita, L. M., Cheng, J. J., Yesavage, J. A., Helmer, D. A., Reinhard, M. J., Ashford, J. W., Adamson, M. M. 2016; 53 (6): 781-796

  Abstract

  Veterans who have been deployed to combat often have complex medical histories including some combination of traumatic brain injury (TBI); mental health problems; and other chronic, medically unexplained symptoms (i.e., chronic multisymptom illness [CMI] clusters). How these multiple pathologies relate to functional health is unclear. In the current study, 120 Veterans (across multiple combat cohorts) underwent comprehensive clinical evaluations and completed self-report assessments of mental health symptoms (Patient Health Questionnaire-2 [PHQ-2], PTSD Checklist-Civilian Version [PCL-C]) and functional health (Veterans Rand 36-Item Health Survey). Canonical correlation and regression modeling using split-sample permutation tests revealed that the PHQ-2/PCL-C composite variable (among TBI severity and number of problematic CMI clusters) was the primary predictor of multiple functional health domains. Two subscales, Bodily Pain and General Health, were associated with multiple predictors (TBI, PHQ-2/PCL-C, and CMI; and PHQ-2/PCL-C and CMI, respectively), demonstrating the multifaceted nature of how distinct medical problems might uniquely and collectively impair aspects of functional health. Apart from these findings, however, TBI and CMI were not predictors of any other aspects of functional health. Taken together, our findings suggest that mental health problems might exert ubiquitous influence over multiple domains of functional health. Thus, screening of mental health problems and education and promotion of mental health resources can be important to the treatment and care of Veterans.

  View details for DOI 10.1682/JRRD.2015.07.0146

  View details for PubMedID 28273324

• Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial INTERNATIONAL PSYCHOGERIATRICS Rosenberg, P. B., Drye, L. T., Porsteinsson, A. P., Pollock, B. G., Devanand, D. P., Frangakis, C., Ismail, Z., Marano, C., Meinert, C. L., Mintzer, J. E., Munro, C. A., Pelton, G., Rabins, P. V., Schneider, L. S., Shade, D. M., Weintraub, D., Newell, J., Yesavage, J., Lyketsos, C. G. 2015; 27 (12): 2059-2067

  Abstract

  Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.

  View details for DOI 10.1017/S1041610215001106

  View details for Web of Science ID 000364938400015

  View details for PubMedID 26305876

  View details for PubMedCentralID PMC4669064

• Time to Response to Citalopram Treatment for Agitation in Alzheimer Disease AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Weintraub, D., Drye, L. T., Porsteinsson, A. P., Rosenberg, P. B., Pollock, B. G., Devanand, D. P., Frangakis, C., Ismail, Z., Marano, C., Meinert, C. L., Mintzer, J. E., Munro, C. A., Pelton, G., Rabins, P. V., Schneider, L. S., Shade, D. M., Yesavage, J., Lyketsos, C. G. 2015; 23 (11): 1127-1133

  Abstract

  Agitation is a common and significant problem in Alzheimer disease (AD). In the recent Citalopram for Agitation in Alzheimer's Disease (CitAD) study, citalopram was efficacious for the treatment of AD agitation. Here we examined the time course and predictors of response to treatment.Response in CitAD was defined as a modified Alzheimer Disease Cooperative Study Clinical Global Impression of Change (CGIC) score of 1 or 2 or a Neurobehavioral Rating Scale agitation subscale (NBRS-A) score reduction ≥ 50% from baseline. "Stable early response" was defined as meeting the aforementioned criteria at both weeks 3 and 9, "late response" was response at week 9 but not at week 3, and "unstable response" was response at week 3 but not at week 9.In the primary analyses, citalopram was superior to placebo on both the CGIC and the NBRS-A response measures. Little between-group differences were found in response rates in the first 3 weeks of the study (21% versus 19% on the CGIC). Citalopram patients were more likely than placebo patients to be a late responder (18% versus 8% on CGIC, Fisher's exact p = 0.09; 31% versus 15% on NBRS-A, Fisher's exact p = 0.02). Approximately half of citalopram responders (45%-56%) at end of study achieved response later in the study compared with 30%-44% of placebo responders.Treatment with citalopram for agitation in AD needs to be at least 9 weeks in duration to allow sufficient time for full response. Study duration is an important factor to consider in the design of clinical trials for agitation in AD.

  View details for DOI 10.1016/j.jagp.2015.05.006

  View details for Web of Science ID 000365588900004

  View details for PubMedID 26238225

  View details for PubMedCentralID PMC4653092

• The STEP Model: Characterizing Simultaneous Time Effects on Practice for Flight Simulator Performance Among Middle-Aged and Older Pilots PSYCHOLOGY AND AGING Kennedy, Q., Taylor, J., Noda, A., Yesavage, J., Lazzeroni, L. C. 2015; 30 (3): 699-711

  Abstract

  Understanding the possible effects of the number of practice sessions (practice) and time between practice sessions (interval) among middle-aged and older adults in real-world tasks has important implications for skill maintenance. Prior training and cognitive ability may impact practice and interval effects on real-world tasks. In this study, we took advantage of existing practice data from 5 simulated flights among 263 middle-aged and older pilots with varying levels of flight expertise (defined by U.S. Federal Aviation Administration proficiency ratings). We developed a new Simultaneous Time Effects on Practice (STEP) model: (a) to model the simultaneous effects of practice and interval on performance of the 5 flights, and (b) to examine the effects of selected covariates (i.e., age, flight expertise, and 3 composite measures of cognitive ability). The STEP model demonstrated consistent positive practice effects, negative interval effects, and predicted covariate effects. Age negatively moderated the beneficial effects of practice. Additionally, cognitive processing speed and intraindividual variability (IIV) in processing speed moderated the benefits of practice and/or the negative influence of interval for particular flight performance measures. Expertise did not interact with practice or interval. Results indicated that practice and interval effects occur in simulated flight tasks. However, processing speed and IIV may influence these effects, even among high-functioning adults. Results have implications for the design and assessment of training interventions targeted at middle-aged and older adults for complex real-world tasks. (PsycINFO Database Record

  View details for DOI 10.1037/pag0000043

  View details for Web of Science ID 000360585600020

  View details for PubMedCentralID PMC4556540

• The STEP model: Characterizing simultaneous time effects on practice for flight simulator performance among middle-aged and older pilots. Psychology and aging Kennedy, Q., Taylor, J., Noda, A., Yesavage, J., Lazzeroni, L. C. 2015; 30 (3): 699-711

  Abstract

  Understanding the possible effects of the number of practice sessions (practice) and time between practice sessions (interval) among middle-aged and older adults in real-world tasks has important implications for skill maintenance. Prior training and cognitive ability may impact practice and interval effects on real-world tasks. In this study, we took advantage of existing practice data from 5 simulated flights among 263 middle-aged and older pilots with varying levels of flight expertise (defined by U.S. Federal Aviation Administration proficiency ratings). We developed a new Simultaneous Time Effects on Practice (STEP) model: (a) to model the simultaneous effects of practice and interval on performance of the 5 flights, and (b) to examine the effects of selected covariates (i.e., age, flight expertise, and 3 composite measures of cognitive ability). The STEP model demonstrated consistent positive practice effects, negative interval effects, and predicted covariate effects. Age negatively moderated the beneficial effects of practice. Additionally, cognitive processing speed and intraindividual variability (IIV) in processing speed moderated the benefits of practice and/or the negative influence of interval for particular flight performance measures. Expertise did not interact with practice or interval. Results indicated that practice and interval effects occur in simulated flight tasks. However, processing speed and IIV may influence these effects, even among high-functioning adults. Results have implications for the design and assessment of training interventions targeted at middle-aged and older adults for complex real-world tasks. (PsycINFO Database Record

  View details for DOI 10.1037/pag0000043

  View details for PubMedID 26280383

  View details for PubMedCentralID PMC4556540

• Sleep Quality and Risk of Dementia Among Older Male Veterans AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Yaffe, K., Nettiksimmons, J., Yesavage, J., Byers, A. 2015; 23 (6): 651-654

  Abstract

  To determine whether a diagnosis of sleep disturbance is associated with dementia in older veterans.For this retrospective cohort study, we obtained medical record data from the Department of Veterans Affairs National Patient Care Database for 200,000 randomly selected veterans aged 55 years and older. Prevalent cases of dementia from the baseline period (2000-2003) were excluded, leaving an analytic sample of 179,738 male veterans. Follow-up took place from 2004 to 2011. The primary outcome was all-cause dementia, ascertained using International Classification of Disease, Ninth Revision codes. Sleep disturbance, the primary predictor, was also ascertained using these codes.After adjusting for potential confounders, those with sleep disturbance had a 27% increased risk of dementia (hazard ratio: 1.27; 95% confidence interval: 1.20-1.34).Sleep disturbance was associated with increased risk of dementia among a large cohort of older, primarily male veterans.

  View details for DOI 10.1016/j.jagp.2015.02.008

  View details for Web of Science ID 000354338100013

  View details for PubMedID 25794635

• Personalizing the Treatment of Depression: Emotional Reactivity and Early Life Stress Predict Antidepressant Outcomes Goldstein-Piekarski, A. N., Yesavage, J., Schatzberg, A., Etkin, A., O'hara, R., Suppes, T., Korgaonkar, M., Williams, L. ELSEVIER SCIENCE INC. 2015

  View details for Web of Science ID 000352207501255

• Donepezil treatment in ethnically diverse patients with Alzheimer disease. American journal of geriatric psychiatry Tinklenberg, J. R., Kraemer, H. C., Yaffe, K., O'Hara, R., Ringman, J. M., Ashford, J. W., Yesavage, J. A., Taylor, J. L. 2015; 23 (4): 384-390

  Abstract

  To compare the outcome of donepezil treatment in ethnically diverse Alzheimer disease (AD) patients with ethnically diverse AD patients who did not receive donepezil.Patients meeting NINCDS-ADRA criteria for probable or possible AD from a consortium of California sites were systematically followed for at least 1 year in this prospective, observational study. Their treatment regimens, including prescription of donepezil, were determined by their individual physician according to his or her usual criteria. Patients self-identified their ethnicity.The 64 ethnically diverse AD patients who completed the study and received donepezil treatment had an average 1-year decline of 2.30 points (standard deviation: 3.9) on the 30-point Mini-Mental State Exam compared with a 1.70-point (standard deviation: 4.2) decline in the 74 ethnically diverse completers who received no donepezil or other anti-AD drugs during the study period. This difference was not statistically significant. The overall Cohen effect size of this treatment-associated difference was estimated at -0.15. After using propensity analyses and other techniques to assess factors that could bias prescribing decisions, the lack of benefits associated with donepezil treatment remained. The lack of donepezil benefits also remained when more traditional analyses were applied to these data.Ethnically diverse AD patients in this study apparently did not benefit from 1 year of donepezil treatment. These unpromising results are in contrast to modest benefits of donepezil treatment measured in a directly comparable California study involving white non-Latino AD patients.

  View details for DOI 10.1016/j.jagp.2014.09.007

  View details for PubMedID 25747405

• Verbal Naming Test for Use with Older Adults: Development and Initial Validation JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY Yochim, B. P., Beaudreau, S. A., Fairchild, J. K., Yutsis, M. V., Raymond, N., Friedman, L., Yesavage, J. 2015; 21 (3): 239-248

  Abstract

  Naming or word-finding tasks are a mainstay of the typical neuropsychological evaluation, particularly with older adults. However, many older adults have significant visual impairment and there are currently no such word-finding tasks developed for use with older visually impaired populations. This study presents a verbal, non-visual measure of word-finding for use in the evaluation of older adults with possible dysnomia. Stimuli were chosen based on their frequency of usage in everyday spoken language. A 60-item scale was created and given to 131 older Veterans. Rasch analyses were conducted and differential item functioning assessed to eliminate poorly-performing items. The final 55-item scale had a coefficient alpha of 0.84 and correlated with the Neuropsychological Assessment Battery Naming test, r=0.84, p<.01, Delis-Kaplan Executive Function System (D-KEFS) Category Fluency, r=0.45, p<.01, and the D-KEFS Letter Fluency, r=0.40, p<.01. ROC analyses found the measure to have sensitivity of 79% and specificity of 85% for detecting dysnomia. Patients with dysnomia performed worse on the measure than patients with intact word-finding, t(84)=8.2, p<.001. Patients with no cognitive impairment performed significantly better than patients with mild cognitive impairment, who performed significantly better than patients with dementia. This new measure shows promise in the neuropsychological evaluation of word-finding ability in older adults with or without visual impairment. Future directions include the development of a shorter version and the generation of additional normative data.

  View details for DOI 10.1017/S1355617715000120

  View details for Web of Science ID 000354027000007

  View details for PubMedID 25801537

• Increased Prevalence of Sleep Disordered Breathing in Older Veterans with PTSD Yesavage, J. A., Iqbal, N., Goodale, G., Noda, A., Hernandez, B., Cheng, J., Zeitzer, J. M., Friedman, L., Kinoshita, L. M. ELSEVIER SCIENCE INC. 2015: S180–S181

  View details for DOI 10.1016/j.jagp.2014.12.189

  View details for Web of Science ID 000350829500181

• The impact of depression on Veterans with PTSD and traumatic brain injury: A diffusion tensor imaging study. Biological psychology Isaac, L., Main, K. L., Soman, S., Gotlib, I. H., Furst, A. J., Kinoshita, L. M., Fairchild, J. K., Yesavage, J. A., Ashford, J. W., Bayley, P. J., Adamson, M. M. 2015; 105: 20-28

  Abstract

  A significant proportion of military personnel deployed in support of Operation Enduring Freedom and Operation Iraqi Freedom were exposed to war-zone events associated with traumatic brain injury (TBI), depression (DEP) and posttraumatic stress disorder (PTSD). The co-occurrence of TBI, PTSD and DEP in returning Veterans has recently increased research and clinical interest. This study tested the hypothesis that white matter abnormalities are further impacted by depression. Of particular relevance is the uncinate fasciculus (UF), which is a key fronto-temporal tract involved in mood regulation, and the cingulum; a tract that connects to the hippocampus involved in memory integration. Diffusion tensor imaging (DTI) was performed on 25 patients with a combination of PTSD, TBI and DEP and 20 patients with PTSD and TBI (no DEP). Microstructural changes of white matter were found in the cingulum and UF. Fractional anisotropy (FA) was lower in Veterans with DEP compared to those without DEP.

  View details for DOI 10.1016/j.biopsycho.2014.12.011

  View details for PubMedID 25559772

• Comparison of the Effectiveness of Cognitive Behavioral Therapy for Depression among Older Versus Younger Veterans: Results of a National Evaluation. journals of gerontology. Series B, Psychological sciences and social sciences Karlin, B. E., Trockel, M., Brown, G. K., Gordienko, M., Yesavage, J., Taylor, C. B. 2015; 70 (1): 3-12

  Abstract

  The effectiveness of cognitive behavioral therapy for depression (CBT-D) among older adults in routine clinical settings has received limited attention. The current article examines and compares outcomes of older versus younger veterans receiving CBT-D nationally.Patient outcomes were assessed using the Beck Depression Inventory-II and World Health Organization Quality of Life-BREF. Therapeutic alliance was assessed using the Working Alliance Inventory-Short Revised.A total of 764 veterans aged 18-64 and 100 veterans aged 65+ received CBT-D; 68.0% of older and 68.3% of younger patients completed all sessions or finished early due to symptom relief, and mean depression scores declined from 27.0 (standard deviation [SD] = 10.7) to 16.2 (SD = 12.4) in the older group and from 29.1 (SD = 11.2) to 17.8 (SD = 13.5) in the younger group. Within-group effect sizes were d = 1.01 for both groups. Significant increases in quality of life and therapeutic alliance were observed for both groups.CBT-D resulted in significant improvements in depression and quality of life among older patients. Outcomes and rate of attrition were equivalent to younger patients. Findings indicate that CBT-D is an effective and acceptable treatment for older veterans in real-world settings with often high levels of depression.

  View details for DOI 10.1093/geronb/gbt096

  View details for PubMedID 24218096

• Higher Landing Accuracy in Expert Pilots is Associated with Lower Activity in the Caudate Nucleus PLOS ONE Adamson, M. M., Taylor, J. L., Heraldez, D., Khorasani, A., Noda, A., Hernandez, B., Yesavage, J. A. 2014; 9 (11)

  Abstract

  The most common lethal accidents in General Aviation are caused by improperly executed landing approaches in which a pilot descends below the minimum safe altitude without proper visual references. To understand how expertise might reduce such erroneous decision-making, we examined relevant neural processes in pilots performing a simulated landing approach inside a functional MRI scanner. Pilots (aged 20-66) were asked to "fly" a series of simulated "cockpit view" instrument landing scenarios in an MRI scanner. The scenarios were either high risk (heavy fog-legally unsafe to land) or low risk (medium fog-legally safe to land). Pilots with one of two levels of expertise participated: Moderate Expertise (Instrument Flight Rules pilots, n = 8) or High Expertise (Certified Instrument Flight Instructors or Air-Transport Pilots, n = 12). High Expertise pilots were more accurate than Moderate Expertise pilots in making a "land" versus "do not land" decision (CFII: d' = 3.62 ± 2.52; IFR: d' = 0.98 ± 1.04; p<.01). Brain activity in bilateral caudate nucleus was examined for main effects of expertise during a "land" versus "do not land" decision with the no-decision control condition modeled as baseline. In making landing decisions, High Expertise pilots showed lower activation in the bilateral caudate nucleus (0.97 ± 0.80) compared to Moderate Expertise pilots (1.91 ± 1.16) (p<.05). These findings provide evidence for increased "neural efficiency" in High Expertise pilots relative to Moderate Expertise pilots. During an instrument approach the pilot is engaged in detailed examination of flight instruments while monitoring certain visual references for making landing decisions. The caudate nucleus regulates saccade eye control of gaze, the brain area where the "expertise" effect was observed. These data provide evidence that performing "real world" aviation tasks in an fMRI provide objective data regarding the relative expertise of pilots and brain regions involved in it.

  View details for DOI 10.1371/journal.pone.0112607

  View details for Web of Science ID 000349145400020

  View details for PubMedID 25426935

  View details for PubMedCentralID PMC4245093

• Nocturia Reported in Nightly Sleep Diaries: Common Occurrence With Significant Implications? HEALTH PSYCHOLOGY Bliwise, D. L., Friedman, L., Hernandez, B., Zeitzer, J. M., Kushida, C. A., Yesavage, J. A. 2014; 33 (11): 1362-1365

  Abstract

  Nocturia (nocturnal awakenings associated with urination) is so common a nocturnal behavior that its association with poor sleep is often overlooked. This study examined nocturia and its potential role in poor sleep by examining reported nightly awakenings and associated bathroom trips.Sleep diaries were kept by 119 adults with poor sleep for intervals up to 14 days. Diaries collected data on nightly number of awakenings and nightly number of bathroom trips. The proportion of nocturnal awakenings accompanied by voiding for each night was calculated and averaged within each individual. Demographics and various health conditions were examined in relation to this measure.Nocturia was defined when at least two-thirds of all awakenings were associated with nocturnal voiding. Absence of nocturia was defined when less than one-third of awakenings were associated with voiding. Remaining cases were defined as having possible nocturia. Estimates of nocturia derived from prestudy screening were related to nocturia as defined by sleep diaries. Neither gender nor sleep apnea was associated with nocturia. Unadjusted analyses indicated that individuals with nocturia were more likely to have arthritis and attribute their nighttime awakenings to urge to void than individuals without nocturia.Nocturia is an exceedingly common phenomenon and may be associated with multiple morbidities. RESULTS are discussed in terms of causality and whether the perceived urge to void precedes or follows nocturnal awakening. Correlates of nocturia have important implications, because they can inform interventions that target brain (e.g., cognitive-behavioral treatments for insomnia, sedative/hypnotic medications) versus bladder (e.g., bladder control exercises, medications affecting urine production or urgency).

  View details for DOI 10.1037/a0034401

  View details for Web of Science ID 000344010300011

  View details for PubMedCentralID PMC4119089

• Integration of Clinical and Research Neuroimaging to Understand Traumatic Brain Injury in the Veteran Population. Federal practitioner : for the health care professionals of the VA, DoD, and PHS Adamson, M. M., Main, K., Kong, J. Y., Soman, S., Furst, A., Kinoshita, L., Yesavage, J., Ashford, J. W. 2014; 31: 3S-7S

  Abstract

  There is a complex relationship between posttraumatic stress disorder and traumatic brain injury. To understand and treat these conditions, it is necessary to apply an integrated physical and mental health care approach to postdeployment care.

  View details for PubMedID 26705383

• Recommendations for the use of Serious Games in people with Alzheimer's Disease, related disorders and frailty FRONTIERS IN AGING NEUROSCIENCE Robert, P. H., Koenig, A., Amieva, H., Andrieu, S., Bremond, F., Bullock, R., Ceccaldi, M., Dubois, B., Gauthier, S., Kenigsberg, P., Nave, S., Orgogozo, J. M., Piano, J., Benoit, M., Touchon, J., Vellas, B., Yesavage, J., Manera, V. 2014; 6

  Abstract

  Alzheimer's disease and other related disorders (ADRD) represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments to assess the disease severity and progression, as well as to improve its treatment, stimulation, and rehabilitation. This is the underlying idea for the development of Serious Games (SG). These are digital applications specially adapted for purposes other than entertaining; such as rehabilitation, training and education. Recently, there has been an increase of interest in the use of SG targeting patients with ADRD. However, this field is completely uncharted, and the clinical, ethical, economic and research impact of the employment of SG in these target populations has never been systematically addressed. The aim of this paper is to systematically analyze the Strengths, Weaknesses, Opportunities, and Threats (SWOT) of employing SG with patients with ADRD in order to provide practical recommendations for the development and use of SG in these populations. These analyses and recommendations were gathered, commented on and validated during a 2-round workshop in the context of the 2013 Clinical Trial of Alzheimer's Disease (CTAD) conference, and endorsed by stakeholders in the field. The results revealed that SG may offer very useful tools for professionals involved in the care of patients suffering from ADRD. However, more interdisciplinary work should be done in order to create SG specifically targeting these populations. Furthermore, in order to acquire more academic and professional credibility and acceptance, it will be necessary to invest more in research targeting efficacy and feasibility. Finally, the emerging ethical challenges should be considered a priority.

  View details for DOI 10.3389/fnagi.2014.00054

  View details for Web of Science ID 000333213700001

  View details for PubMedID 24715864

  View details for PubMedCentralID PMC3970032

• Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA-the journal of the American Medical Association Porsteinsson, A. P., Drye, L. T., Pollock, B. G., Devanand, D. P., Frangakis, C., Ismail, Z., Marano, C., Meinert, C. L., Mintzer, J. E., Munro, C. A., Pelton, G., Rabins, P. V., Rosenberg, P. B., Schneider, L. S., Shade, D. M., Weintraub, D., Yesavage, J., Lyketsos, C. G. 2014; 311 (7): 682-691

  Abstract

  Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer disease. Pharmacological treatment options, including antipsychotics are not satisfactory.The primary objective was to evaluate the efficacy of citalopram for agitation in patients with Alzheimer disease. Key secondary objectives examined effects of citalopram on function, caregiver distress, safety, cognitive safety, and tolerability.The Citalopram for Agitation in Alzheimer Disease Study (CitAD) was a randomized, placebo-controlled, double-blind, parallel group trial that enrolled 186 patients with probable Alzheimer disease and clinically significant agitation from 8 academic centers in the United States and Canada from August 2009 to January 2013.Participants (n = 186) were randomized to receive a psychosocial intervention plus either citalopram (n = 94) or placebo (n = 92) for 9 weeks. Dosage began at 10 mg per day with planned titration to 30 mg per day over 3 weeks based on response and tolerability.Primary outcome measures were based on scores from the 18-point Neurobehavioral Rating Scale agitation subscale (NBRS-A) and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC). Other outcomes were based on scores from the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory (NPI), ability to complete activities of daily living (ADLs), caregiver distress, cognitive safety (based on scores from the 30-point Mini Mental State Examination [MMSE]), and adverse events.Participants who received citalopram showed significant improvement compared with those who received placebo on both primary outcome measures. The NBRS-A estimated treatment difference at week 9 (citalopram minus placebo) was -0.93 (95% CI, -1.80 to -0.06), P = .04. Results from the mADCS-CGIC showed 40% of citalopram participants having moderate or marked improvement from baseline compared with 26% of placebo recipients, with estimated treatment effect (odds ratio [OR] of being at or better than a given CGIC category) of 2.13 (95% CI, 1.23-3.69), P = .01. Participants who received citalopram showed significant improvement on the CMAI, total NPI, and caregiver distress scores but not on the NPI agitation subscale, ADLs, or in less use of rescue lorazepam. Worsening of cognition (-1.05 points; 95% CI, -1.97 to -0.13; P = .03) and QT interval prolongation (18.1 ms; 95% CI, 6.1-30.1; P = .01) were seen in the citalopram group.Among patients with probable Alzheimer disease and agitation who were receiving psychosocial intervention, the addition of citalopram compared with placebo significantly reduced agitation and caregiver distress; however, cognitive and cardiac adverse effects of citalopram may limit its practical application at the dosage of 30 mg per day.clinicaltrials.gov Identifier: NCT00898807.

  View details for DOI 10.1001/jama.2014.93

  View details for PubMedID 24549548

• Effects of body mass index-related disorders on cognition: preliminary results. Diabetes, metabolic syndrome and obesity : targets and therapy Yesavage, J. A., Kinoshita, L. M., Noda, A., Lazzeroni, L. C., Fairchild, J. K., Taylor, J., Kulick, D., Friedman, L., Cheng, J., Zeitzer, J. M., O'Hara, R. 2014; 7: 145-151

  Abstract

  Well-known risk factors for cognitive impairment are also associated with obesity. Research has highlighted genetic risk factors for obesity, yet the relationship of those risk factors with cognitive impairment is unknown. The objective of this study was to determine the associations between cognition, hypertension, diabetes, sleep-disordered breathing, and obesity. Genetic risk factors of obesity were also examined.The sample consisted of 369 nondemented individuals aged 50 years or older from four community cohorts. Primary outcome measures included auditory verbal memory, as measured by the Rey Auditory Verbal Learning Test, and executive functioning, as measured by the Color-Word Interference Test of the Delis-Kaplan Executive Function System battery. Apnea-hypopnea index indicators were determined during standard overnight polysomnography. Statistical analyses included Pearson correlations and linear regressions.Poor executive function and auditory verbal memory were linked to cardiovascular risk factors, but not directly to obesity. Genetic factors appeared to have a small but measureable association to obesity.A direct linkage between obesity and poor executive function and auditory verbal memory is difficult to discern, possibly because nonobese individuals may show cognitive impairment due to insulin resistance and the "metabolic syndrome".

  View details for DOI 10.2147/DMSO.S60294

  View details for PubMedID 24855383

• Changes in QTc Interval in the Citalopram for Agitation in Alzheimer's Disease (CitAD) Randomized Trial. PloS one Drye, L. T., Spragg, D., Devanand, D. P., Frangakis, C., Marano, C., Meinert, C. L., Mintzer, J. E., Munro, C. A., Pelton, G., Pollock, B. G., Porsteinsson, A. P., Rabins, P. V., Rosenberg, P. B., Schneider, L. S., Shade, D. M., Weintraub, D., Yesavage, J., Lyketsos, C. G. 2014; 9 (6)

  Abstract

  A Food and Drug Administration (FDA) safety communication in August 2011 warned that citalopram was associated with a dose dependent risk of QT prolongation and recommended dose restriction in patients over the age of 60 but did not provide data for this age group.CitAD was a randomized, double-masked, placebo-controlled, multicenter clinical trial for agitation in Alzheimer's disease (AD). Participants were assigned to citalopram (target dose of 30 mg/day) or placebo in a 1∶1 ratio. 186 people, 181 of whom were over the age of 60, having probable AD with clinically significant agitation were recruited from September 2009 to January 2013. After the FDA safety communication about citalopram, ECG was added to the required study procedures before enrollment and repeated at week 3 to monitor change in QTc interval. Forty-eight participants were enrolled after enhanced monitoring began.Citalopram treatment was associated with a larger increase in QTc interval than placebo (difference in week 3 QTc adjusting for baseline QTc: 18.1 ms [95% CI: 6.1, 30.1]; p = 0.004). More participants in the citalopram group had an increase ≥30 ms from baseline to week 3 (7 in citalopram versus 1 in placebo; Fisher's exact p = 0.046), but only slightly more in the citalopram group met a gender-specific threshold for prolonged QTc (450 ms for males; 470 ms for females) at any point during follow-up (3 in citalopram versus 1 in placebo, Fisher's exact p = 0.611). One of the citalopram participants who developed prolonged QTc also displayed ventricular bigeminy. No participants in either group had a cardiovascular-related death.Citalopram at 30 mg/day was associated with improvement in agitation in patients with AD but was also associated with QT prolongation.ClinicalTrials.gov NCT00898807.

  View details for DOI 10.1371/journal.pone.0098426

  View details for PubMedID 24914549

  View details for PubMedCentralID PMC4051660

• Longitudinal assessment of sleep disordered breathing in Vietnam veterans with post-traumatic stress disorder. Nature and science of sleep Yesavage, J. A., Kinoshita, L. M., Noda, A., Lazzeroni, L. C., Fairchild, J. K., Friedman, L., Sekhon, G., Thompson, S., Cheng, J., Zeitzer, J. M. 2014; 6: 123-127

  Abstract

  Previous work has demonstrated the relatively high prevalence of risk factors for cognitive impairment, such as sleep disordered breathing (SDB) and obesity, in Vietnam War era veterans with post-traumatic stress disorder (PTSD). No data are currently available on the longitudinal stability of SDB as a risk factor for cognitive decline in that population, which this study now reports.Sample consisted of 48 veterans of the Vietnam War with PTSD who completed longitudinal sleep assessments over a 3-year period. The primary outcome measure, the Apnea-Hypopnea Index (AHI) indicator, was determined during standard overnight polysomnography. Body mass index (BMI) was calculated using standard measurements. Measures of cognitive function tapped auditory verbal memory as measured by the Rey Auditory Verbal Learning Test and executive functioning as measured by the Color-Word Interference Test of the Delis-Kaplan Executive Function System battery. Statistical analyses included mixed effects modeling.In this sample, AHI increased significantly by 2.19 points per year (β=2.19; P<0.005). AHI worsened over the 3-year period, increasing from a mean of 18.7±15.7 to 24.7±17.4 points. Neither BMI nor cognition showed significant change over the 3-year period.SDB worsened in a group of veterans of the Vietnam War with PTSD over a 3-year period. The worsening of SDB over time suggests the need for appropriate countermeasures in populations at risk for progression of the condition.

  View details for DOI 10.2147/NSS.S65034

  View details for PubMedID 25378962

  View details for PubMedCentralID PMC4219637

• Recommendations for ICT use in Alzheimer's disease assessment: Monaco CTAD expert meeting JOURNAL OF NUTRITION HEALTH & AGING Robert, P. H., Konig, A., Andrieu, S., Bremond, F., Chemin, I., Chung, P. C., Dartigues, J. F., Dubois, B., Feutren, G., Guillemaud, R., Kenisberg, P. A., Nave, S., Vellas, B., Verhey, F., Yesavage, J., Mallea, P. 2013; 17 (8): 653-660

  Abstract

  Alzheimer disease (AD) and other related dementia represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments for assessing disease severity and disease progression to optimize patient's care and support to care providers, and also provide better tools for clinical research. In this area, Information and Communication Technologies (ICT) are of particular interest. Such techniques enable accurate and standardized assessments of patients' performance and actions in real time and real life situations. The aim of this article is to provide basic recommendation concerning the development and the use of ICT for Alzheimer's disease and related disorders. During he ICT and Mental Health workshop (CTAD meeting held in Monaco on the 30th October 2012) an expert panel was set up to prepare the first recommendations for the use of ICT in dementia research. The expert panel included geriatrician, epidemiologist, neurologist, psychiatrist, psychologist, ICT engineers, representatives from the industry and patient association. The recommendations are divided into three sections corresponding to 1/ the clinical targets of interest for the use of ICT, 2/ the conditions, the type of sensors and the outputs (scores) that could be used and obtained, 3/ finally the last section concerns specifically the use of ICT within clinical trials.

  View details for DOI 10.1007/s12603-013-0046-3

  View details for Web of Science ID 000325432400003

  View details for PubMedID 24097018

• Intraindividual variability in basic reaction time predicts middle-aged and older pilots' flight simulator performance. journals of gerontology. Series B, Psychological sciences and social sciences Kennedy, Q., Taylor, J., Heraldez, D., Noda, A., Lazzeroni, L. C., Yesavage, J. 2013; 68 (4): 487-494

  Abstract

  ObjectivesIntraindividual variability (IIV) is negatively associated with cognitive test performance and is positively associated with age and some neurological disorders. We aimed to extend these findings to a real-world task, flight simulator performance. We hypothesized that IIV predicts poorer initial flight performance and increased rate of decline in performance among middle-aged and older pilots.MethodTwo-hundred and thirty-six pilots (40-69 years) completed annual assessments comprising a cognitive battery and two 75-min simulated flights in a flight simulator. Basic and complex IIV composite variables were created from measures of basic reaction time and shifting and divided attention tasks. Flight simulator performance was characterized by an overall summary score and scores on communication, emergencies, approach, and traffic avoidance components. RESULTS: Although basic IIV did not predict rate of decline in flight performance, it had a negative association with initial performance for most flight measures. After taking into account processing speed, basic IIV explained an additional 8%-12% of the negative age effect on initial flight performance.DiscussionIIV plays an important role in real-world tasks and is another aspect of cognition that underlies age-related differences in cognitive performance.

  View details for DOI 10.1093/geronb/gbs090

  View details for PubMedID 23052365

• Effectiveness of acceptance and commitment therapy for depression: Comparison among older and younger veterans AGING & MENTAL HEALTH Karlin, B. E., Walser, R. D., Yesavage, J., Zhang, A., Trockel, M., Taylor, C. B. 2013; 17 (5): 555-563

  Abstract

  Limited data exist on outcomes of older adults receiving psychotherapy for depression in real-world settings. Acceptance and Commitment Therapy for depression (ACT-D) offers potential utility for older individuals who may experience issues of loss, reduced control, and other life changes. The present article examines and compares outcomes of older and younger Veterans receiving ACT-D nationally in the U.S. Department of Veterans Affairs health care system.Patient outcomes were assessed using the Beck Depression Inventory-Second Edition and the World Health Organization Quality of Life-BREF. Therapeutic alliance was assessed using the Working Alliance Inventory-Short Revised.Six hundred fifty-five Veterans aged 18-64 and 76 Veterans aged 65+ received ACT-D. Seventy-eight percent of older and 67% of younger patients completed all sessions or finished early. Mean depression scores declined from 28.4 (SD = 11.4) to 17.5 (SD = 12.0) in the older group and 30.3 (SD = 10.6) to 19.1 (SD = 14.3) in the younger group. Within-group effect sizes were d = .95 and d = 1.06 for the two age groups, respectively. Quality of life and therapeutic alliance also increased during treatment.The findings suggest that ACT-D is an effective and acceptable treatment for older Veterans treated in routine clinical settings, including those with high levels of depression.

  View details for DOI 10.1080/13607863.2013.789002

  View details for Web of Science ID 000320913300005

  View details for PubMedID 23607328

• Phenotyping apathy in individuals with Alzheimer disease using functional principal component analysis. American journal of geriatric psychiatry Zeitzer, J. M., David, R., Friedman, L., Mulin, E., Garcia, R., Wang, J., Yesavage, J. A., Robert, P. H., Shannon, W. 2013; 21 (4): 391-397

  Abstract

  To determine if there is a specific pattern of gross motor activity associated with apathy in individuals with Alzheimer disease (AD).Examination of ad libitum 24-hour ambulatory gross motor activity patterns.Community-dwelling, outpatient.Ninety-two individuals with AD, 35 of whom had apathy.Wrist actigraphy data were collected and examined using functional principal component analysis (fPCA).Individuals with apathy have a different pattern of gross motor activity than those without apathy (first fPCA component, p <0.0001, t = 5.73, df = 90, t test) such that there is a pronounced decline in early afternoon activity in those with apathy. This change in activity is independent of depression (p = 0.68, F[1, 89] = 0.05, analysis of variance). The decline in activity is consistent with an increase in napping. Those with apathy also have an early wake and bedtime (second fPCA component, t = 2.53, df = 90, p <0.05, t test).There is a signature activity pattern in individuals with apathy and AD that is distinct from those without apathy and those with depression. Actigraphy may be a useful adjunctive measurement in the clinical diagnosis of apathy in the context of AD.

  View details for DOI 10.1016/j.jagp.2012.12.012

  View details for PubMedID 23498386

• Which older adults maintain benefit from cognitive training? Use of signal detection methods to identify long-term treatment gains INTERNATIONAL PSYCHOGERIATRICS Fairchild, J. K., Friedman, L., Rosen, A. C., Yesavage, J. A. 2013; 25 (4): 607-616

  Abstract

  Cognitive training has been shown to improve memory in older adults; however, little is known about which individuals benefit from or respond best to training in the long term. Identification of responders' characteristics would help providers match cognitive interventions to individuals to improve their effectiveness. Signal detection methods may prove more informative than more commonly used analytic methods. The goal of the current study is to identify baseline characteristics of long-term treatment responders and of those able to maintain their initial benefit from cognitive training.Participants were 120 non-demented, community-dwelling older adults who had participated in a cognitive training intervention. Tested predictors included both demographic and neurocognitive variables. Primary outcome variables were performance on measures of memory at one-year follow-up.Results of the signal detection analysis indicated that different neurocognitive performances predicted long-term effects of memory training and maintenance of initial treatment response according to different types of to-be-remembered material. Higher baseline scores on tests of associative memory, delayed verbal memory, attention, episodic memory, and younger age were found predictive of long-term response one year later. Higher associative memory scores and lower initial gains at the end of treatment (week 14) predicted successful maintenance of training gains at week 52.To derive long-term benefit from particular cognitive training programs, it appears necessary for older adults to have specific neurocognitive profiles. Further, inclusion of booster sessions to cognitive training programs may assist in maintenance of initial treatment gains.

  View details for DOI 10.1017/S1041610212002049

  View details for Web of Science ID 000315084700009

  View details for PubMedID 23237099

• Management of apathy in nursing homes using a teaching program for care staff: the STIM-EHPAD study INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Leone, E., Deudon, A., Bauchet, M., Laye, M., Bordone, N., Lee, J., Piano, J., Friedman, L., David, R., Delva, F., Brocker, P., Yesavage, J., Robert, P. H. 2013; 28 (4): 383-392

  Abstract

  This study aimed to evaluate the effectiveness of a nursing home (NH) staff education to manage apathy in older individuals with a diagnosis of dementia.Sixteen NHs agreed to participate, and 230 demented apathetic residents were randomly assigned to the reference group (RG) or the intervention group (IG). IG received a month of weekly 4-h training. Qualitative evaluation was performed through interviews and questionnaires regarding work practices and knowledge about dementia. Quantitative evaluation was at baseline, at the end of the training program (week 4), and 3 months after the end of it with the use of the Neuropsychiatric Inventory (NPI), the Apathy Inventory, and two observation scales.In the qualitative evaluation, very few staff responded to the questionnaire. Concerning the difficulty that managing residents' behavioral symptoms presented, aggressiveness was ranked as the most difficult behavior to manage and apathy as the least difficult. In the quantitative evaluation, the results are as follows. NPI: the IG scores increased from baseline to week 4 more than the RG for symptoms belonging to the affective and the psychotic NPI item subgroup. Apathy Inventory: there was a significant decrease of the emotional blunting score dimension in the IG. Group Observation Scale: significant improvement was observed for the emotional blunting dimension in the IG only.Apathy is rarely identified as a problem in NH. Emotional blunting was the only dimension sensitive to change. Failure to improve residents' level of interest could be explained by the difficulties encountered in accessing information regarding the subjects' personal interests. But it remains possible to modify residents' emotional reactivity and staff's perceptions of residents' behaviors and emotions.

  View details for DOI 10.1002/gps.3836

  View details for Web of Science ID 000315958800008

  View details for PubMedID 22700526

• Memantine is Associated with Longer Survival than Donepezil in a Veterans Affairs Prescription Database, 1997 to 2008 JOURNAL OF ALZHEIMERS DISEASE Lazzeroni, L. C., Halbauer, J. D., Ashford, J. W., Noda, A., Hernandez, B., Azor, V., Hozack, N., Hasson, N., Henderson, V. W., Yesavage, J. A., Tinklenberg, J. R. 2013; 36 (4): 791-798

  Abstract

  Alzheimer's disease (AD) shortens life-expectancy, but the effects of pharmacological treatments for this disorder on mortality have not been studied. We compared two commonly prescribed medications, donepezil and memantine, with respect to the length of survival of veterans presumed to have AD. The Computerized Medical Records System at the Veterans Affairs Palo Alto Health Care System (VAPAHCS) was used to identify all patients prescribed these medications between 1997 and 2008. The VAPAHCS approved donepezil in 1997 and memantine in 2004. Kaplan-Meier and Cox regression analyses were used to test for chronological and drug-related associations with survival in 2,083 male veterans aged 55 years and older receiving prescriptions for donepezil, memantine, or both. Overall patient mortality decreased in the 2004 to 2008 era, compared with the 1997 to 2003 era, pre-memantine (HR: 0.75; 95% CI: 0.63, 0.89; p = 0.001). In analyses confined to the 2004 to 2008 era, patients prescribed memantine alone survived significantly longer (median survival 8.9 years) than those prescribed donepezil alone (HR: 2.24; 95% CI: 1.53, 3.28; p < 0.001) or both donepezil and memantine (HR: 1.83; 95% CI: 1.14, 2.94; p = 0.012). While this study has several limitations, these findings suggest that memantine treatment is associated with an increased life-expectancy relative to donepezil treatment. Additional research is needed to replicate these unexpected findings and identify potential mechanisms to explain this apparent association, to establish if the relationship applies to other cholinesterase inhibitors, and to discover whether the findings generalize to women and patient populations with characteristics different from those of the veterans in this study.

  View details for DOI 10.3233/JAD-130662

  View details for Web of Science ID 000322738000016

  View details for PubMedID 23703151

• Nocturia Compounds Nocturnal Wakefulness in Older Individuals with Insomnia JOURNAL OF CLINICAL SLEEP MEDICINE Zeitzer, J. M., Bliwise, D. L., Hernandez, B., Friedman, L., Yesavage, J. A. 2013; 9 (3): 259-262

  Abstract

  To determine the impact of nocturia on objective measures of sleep in older individuals with insomnia.The sleep and toileting patterns of a group of community-dwelling older men (n = 55, aged 64.3 ± 7.52 years) and women (n = 92, aged 62.5 ± 6.73 years) with insomnia were studied for two weeks using sleep logs and one week using actigraphy. The relationships between nocturia and various sleep parameters were analyzed with ANOVA and linear regression.More than half (54.2% ± 39.9%) of all log-reported nocturnal awakenings were associated with nocturia. A greater number of trips to the toilet was associated with worse log-reported restedness (p < 0.01) and sleep efficiency (p < 0.001), as well as increases in actigraph-derived measures of the number and length of nocturnal wake bouts (p < 0.001) and wake after sleep onset (p < 0.001). Actigraph-determined wake bouts were 11.5% ± 23.5% longer on nights on which there was a trip to the toilet and wake after sleep onset was 20.8% ± 33.0% longer during these nights.Nocturia is a common occurrence in older individuals with insomnia and is significantly associated with increased nocturnal wakefulness and decreased subjective restedness after sleep.

  View details for DOI 10.5664/jcsm.2492

  View details for Web of Science ID 000316209800010

  View details for PubMedID 23493881

  View details for PubMedCentralID PMC3578689

• Modeling the effects of obstructive sleep apnea and hypertension in Vietnam veterans with PTSD SLEEP AND BREATHING Kinoshita, L. M., Yesavage, J. A., Noda, A., Jo, B., Hernandez, B., Taylor, J., Zeitzer, J. M., Friedman, L., Fairchild, J. K., Cheng, J., Kuschner, W., O'Hara, R., Holty, J. C., Scanlon, B. K. 2012; 16 (4): 1201-1209

  Abstract

  The present work aimed to extend models suggesting that obstructive sleep apnea (OSA) is associated with worse cognitive performance in community-dwelling older adults. We hypothesized that in addition to indices of OSA severity, hypertension is associated with worse cognitive performance in such adults.The PTSD Apnea Clinical Study recruited 120 community-dwelling, male veterans diagnosed with PTSD, ages 55 and older. The Rey Auditory Verbal Learning Test (RAVLT) and Color-Word Interference Test (CWIT) were measures of auditory verbal memory and executive function, respectively. Apnea-hypopnea index (AHI), minimum and mean pulse oximeter oxygen saturation (min SpO(2), mean SpO(2)) indicators were determined during standard overnight polysomnography. Multivariate linear regression and receiver operating characteristic (ROC) curve analyses were performed.In regression models, AHI (β = -4.099; p < 0.01) and hypertension (β = -4.500; p < 0.05) predicted RAVLT; hypertension alone (β = 9.146; p < 0.01) predicted CWIT. ROC analyses selected min SpO(2) cut-points of 85% for RAVLT (κ = 0.27; χ² = 8.23, p < 0.01) and 80% for CWIT (κ = 0.25; χ² = 12.65, p < 0.01). Min SpO(2) cut-points and hypertension were significant when added simultaneously in a regression model for RAVLT (min SpO(2), β = 4.452; p < 0.05; hypertension, β = -4.332; p < 0.05), and in separate models for CWIT (min SpO(2), β = -8.286; p < 0.05; hypertension, β = -8.993; p < 0.01).OSA severity and presence of self-reported hypertension are associated with poor auditory verbal memory and executive function in older adults.

  View details for DOI 10.1007/s11325-011-0632-8

  View details for Web of Science ID 000311301700038

  View details for PubMedID 22193972

• Pilot Expertise and Hippocampal Size: Associations with Longitudinal Flight Simulator Performance AVIATION SPACE AND ENVIRONMENTAL MEDICINE Adamson, M. M., Bayley, P. J., Scanlon, B. K., Farrell, M. E., Hernandez, B., Weiner, M. W., Yesavage, J. A., Taylor, J. L. 2012; 83 (9): 850-857

  Abstract

  Previous research suggests that the size of the hippocampus can vary in response to intensive training (e.g., during the acquisition of expert knowledge). However, the role of the hippocampus in maintenance of skilled performance is not well understood. The Stanford/Veterans Affairs Aviation MRI Study offers a unique opportunity to observe the interaction of brain structure and multiple levels of expertise on longitudinal flight simulator performance.The current study examined the relationship between hippocampal volume and three levels of aviation expertise, defined by pilot proficiency ratings issued by the U.S. Federal Aviation Administration (11). At 3 annual time points, 60 pilots who varied in their level of aviation expertise (ages ranging from 45 to 69 yr) were tested.At baseline, higher expertise was associated with better flight simulator performance, but not with hippocampal volume. Longitudinally, there was an Expertise x Hippocampal volume interaction, in the direction that a larger hippocampus was associated with better performance at higher levels of expertise.These results are consistent with the notion that expertise in a cognitively demanding domain involves the interplay of acquired knowledge ('mental schemas') and basic hippocampal-dependent processes.

  View details for DOI 10.3357/ASEM.3215.2012

  View details for Web of Science ID 000307919100002

  View details for PubMedID 22946348

• Decreased Daytime Motor Activity Associated With Apathy in Alzheimer Disease: An Actigraphic Study AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY David, R., Mulin, E., Friedman, L., Le Duff, F., Cygankiewicz, E., Deschaux, O., Garcia, R., Yesavage, J. A., Robert, P. H., Zeitzer, J. M. 2012; 20 (9): 806-814

  Abstract

  Across all stages of Alzheimer disease (AD), apathy is the most common neuropsychiatric symptom. Studies using the Neuropsychiatric Inventory (NPI) have found that apathy is present in up to 70% of individuals with Alzheimer disease. One of the main difficulties in assessing apathy and other neuropsychiatric symptoms is the absence of reliable, objective measures. Motor activity assessment using ambulatory actigraphy could provide an indirect, objective evaluation of apathy. The aim of our study was to assess the relationship between apathy and daytime motor activity in AD, using ambulatory actigraphy.One hundred seven AD outpatients wore a wrist actigraph (Motionlogger) during seven consecutive 24-hour periods to evaluate motor activity. Participants were divided into two subgroups according to their apathy subscores on the NPI: individuals with apathy (NPI-apathy subscores >4) and those without. Daytime mean motor activity scores were compared between the two subgroups.Individuals with AD who had symptoms of apathy (n = 43; age = 79 ± 4.7 years; Mini-Mental State Examination = 20.9 ± 4.8) had significantly lower daytime mean motor activity than AD patients without apathy (n = 64; age = 76.3 ± 7.7; Mini-Mental State Examination = 21.5 ± 4.7), while nighttime mean motor activity did not significantly differ between the two subgroups.Ambulatory actigraphy could be added to currently used questionnaires as a simple, objective technique for assessing apathy in the routine assessment of AD patients.

  View details for DOI 10.1097/JGP.0b013e31823038af

  View details for Web of Science ID 000308078500010

  View details for PubMedID 21997602

• Periodic leg movements in sleep in elderly patients with Parkinsonism and Alzheimer's disease EUROPEAN JOURNAL OF NEUROLOGY Bliwise, D. L., Trotti, L. M., Yesavage, J. A., Rye, D. B. 2012; 19 (6): 918-923

  Abstract

    Periodic leg movements in sleep (PLMS) are non-epileptiform, repetitive movements of the lower limbs that have been associated with apparent dopamine deficiency. We hypothesized that elderly patients with a disease characterized primarily by dopamine depletion (Parkinsonism) would have higher rates of PLMS than age-matched controls or a different neurodegenerative condition not primarily involving a hypodopaminergic state, Alzheimer's disease (AD).  We compared rates of PLMS derived from in-laboratory overnight polysomnography in patients with Parkinsonism (n = 79), AD (n = 28), and non-neurologically impaired, community-based controls (n = 187).  Patients with Parkinsonism not receiving levodopa had significantly higher rates of PLMS than did patients with Parkinsonism receiving levodopa as well as higher rates than seen in AD and controls. Other medications did not appear to exert the pronounced effect of levodopa on PLMS in this Parkinsonian patient population. The symptom of leg kicking was reported more frequently in Parkinsonism and was associated with higher rates of PLMS. Caregiver reported leg kicking was unrelated to PLMS in AD. Results are broadly compatible with a dopaminergic hypothesis for PLMS in Parkinsonism. The clinical significance of the negative findings in patients with AD requires further investigation.

  View details for DOI 10.1111/j.1468-1331.2012.03673.x

  View details for Web of Science ID 000303911600024

  View details for PubMedID 22340757

• Brief morning light treatment for sleep/wake disturbances in older memory-impaired individuals and their caregivers SLEEP MEDICINE Friedman, L., Spira, A. P., Hernandez, B., Mather, C., Sheikh, J., Ancoli-Israel, S., Yesavage, J. A., Zeitzer, J. M. 2012; 13 (5): 546-549

  Abstract

  Scheduled exposure to bright light (phototherapy) has been used, with varying degrees of success, to treat sleep disruption in older individuals. Most of these studies have been done in institutional settings and have used several hours of daily light exposure. Such a regimen in the home setting may be untenable, especially when the individual with the sleep disruption has memory impairment and is being cared for by a family member. As such, we examined the effectiveness of a "user-friendly" phototherapy protocol that would be readily usable in the home environment.We exposed a group of 54 older caregiver/care recipient dyads, in which the care recipient had memory impairment, to two weeks of morning bright light phototherapy. Dyads were exposed to either bright white (∼4200 lux) or dim red (∼90 lux) light for 30 min every day, starting within 30 min of rising. All subjects also received sleep hygiene therapy. Objective (actigraphy) and subjective measures of sleep and mood were obtained at baseline and at the end of the two weeks of phototherapy.In care recipients, actigraphy- and log-determined time in bed and total sleep time declined in the active condition (p<0.05, ANOVA); there was no corresponding change in subjective insomnia symptoms (p's>0.37, ANOVA). The decrease in the time in bed was associated with an earlier out of bed time in the morning (p<0.001, Pearson correlation). The decrease in the total sleep time was associated with a decrease in sleep efficiency (p<0.001, Pearson correlation) and an increase in wake after sleep onset (p<0.001, Pearson correlation). In caregivers, there were no differential changes in actigraphic measures of sleep (p's>0.05, ANOVA). Actigraphy-measured wake after sleep onset and sleep efficiency did, however, improve in both conditions, as did sleepiness, insomnia symptoms, and depressive symptomatology (p's<0.05, ANOVA).Exposure to this regimen of phototherapy diminished sleep in older individuals with memory impairments. Their caregivers, however, experienced an improvement in sleep and mood that appeared independent of the phototherapy and likely due to participation in this protocol or the sleep hygiene therapy.

  View details for DOI 10.1016/j.sleep.2011.11.013

  View details for Web of Science ID 000303346800016

  View details for PubMedID 22406033

  View details for PubMedCentralID PMC3337852

• BDNF Polymorphism Predicts the Rate of Decline in Skilled Task Performance and Hippocampal Volume in Healthy Individuals 64th Annual Meeting of the American-Academy-of-Neurology (AAN) Das, D., Sanchez, M., Taylor, J., Noda, A., Yesavage, J., Salehi, A. LIPPINCOTT WILLIAMS & WILKINS. 2012

  View details for Web of Science ID 000303204802378

• Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans. Proceedings of the National Academy of Sciences of the United States of America Bakken, T. E., Roddey, J. C., Djurovic, S., Akshoomoff, N., Amaral, D. G., Bloss, C. S., Casey, B. J., Chang, L., Ernst, T. M., Gruen, J. R., Jernigan, T. L., Kaufmann, W. E., Kenet, T., Kennedy, D. N., Kuperman, J. M., Murray, S. S., Sowell, E. R., Rimol, L. M., Mattingsdal, M., Melle, I., Agartz, I., Andreassen, O. A., Schork, N. J., Dale, A. M., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Liu, E., Montine, T., Gamst, A., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Harvey, D., Kornak, J., Dale, A., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., Alexander, G., DeCarli, C., Bandy, D., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Cairns, N. J., Taylor-Reinwald, L., Trojanowki, J. Q., Shaw, L., Lee, V. M., Korecka, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Kachaturian, Z., Frank, R., Snyder, P. J., Molchan, S., Kaye, J., Quinn, J., Lind, B., Dolen, S., Schneider, L. S., Pawluczyk, S., Spann, B. M., Brewer, J., Vanderswag, H., Heidebrink, J. L., Lord, J. L., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Stern, Y., Honig, L. S., Bell, K. L., Morris, J. C., Ances, B., Carroll, M., Leon, S., Mintun, M. A., Schneider, S., Marson, D., Griffith, R., Clark, D., Grossman, H., Mitsis, E., Romirowsky, A., deToledo-Morrell, L., Shah, R. C., Duara, R., Varon, D., Roberts, P., Albert, M., Onyike, C., Kielb, S., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P. M., Petrella, J. R., Coleman, R. E., Arnold, S. E., Karlawish, J. H., Wolk, D., Smith, C. D., Jicha, G., Hardy, P., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M. S., Brand, C., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Weiner, M., Martin-Cook, K., Devous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Swerdlow, R. H., Apostolova, L., Lu, P. H., Bartzokis, G., Silverman, D. H., Graff-Radford, N. R., Parfitt, F., Johnson, H., Farlow, M. R., Hake, A. M., Matthews, B. R., Herring, S., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Ging-Yuek, Hsiung, R., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Munic, D., Kerwin, D., Mesulam, M., Lipowski, K., Wu, C., Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, R. S., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Frey, M., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M., Belden, C., Jacobson, S., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Obisesan, T. O., Wolday, S., Bwayo, S. K., Lerner, A., Hudson, L., Ogrocki, P., Fletcher, E., Carmichael, O., Olichney, J., Kittur, S., Borrie, M., Lee, T., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Potkin, S. G., Preda, A., Nguyen, D., Tariot, P., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Santulli, R. B., Schwartz, E. S., Sink, K. M., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Mintzer, J., Longmire, C. F., Spicer, K., Finger, E., Rachinsky, I., Drost, D., Jernigan, T., McCabe, C., Grant, E., Ernst, T., Kuperman, J., Chung, Y., Murray, S., Bloss, C., Darst, B., Pritchett, L., Saito, A., Amaral, D., DiNino, M., Eyngorina, B., Sowell, E., Houston, S., Soderberg, L., Kaufmann, W., van Zijl, P., Rizzo-Busack, H., Javid, M., Mehta, N., Ruberry, E., Powers, A., Rosen, B., Gebhard, N., Manigan, H., Frazier, J., Kennedy, D., Yakutis, L., Hill, M., Gruen, J., Bosson-Heenan, J., Carlson, H. 2012; 109 (10): 3985-3990

  Abstract

  Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.

  View details for DOI 10.1073/pnas.1105829109

  View details for PubMedID 22343285

• Sleep-Disordered Breathing in Vietnam Veterans with Posttraumatic Stress Disorder AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Yesavage, J. A., Kinoshita, L. M., Kimball, T., Zeitzer, J., Friedman, L., Noda, A., David, R., Hernandez, B., Lee, T., Cheng, J., O'Hara, R. 2012; 20 (3): 199-204

  Abstract

  : To study the prevalence of sleep-disordered breathing (SDB) in Vietnam- era veterans.: This was an observational study of Vietnam-era veterans using unattended, overnight polysomnography, cognitive testing, and genetic measures.: A sample of 105 Vietnam-era veterans with posttraumatic stress disorder: 69% had an Apnea Hypopnea Index >10. Their mean body mass index was 31, "obese" by Centers for Disease Control and Prevention criteria, and body mass index was significantly associated with Apnea Hypopnea Index (Spearman r = 0.41, N = 97, p < 0.0001). No significant effects of sleep-disordered breathing or apolipoprotein status were found on an extensive battery of cognitive tests.: There is a relatively high prevalence of SDB in these patients which raises the question of to what degree excess cognitive loss in older PTSD patients may be due to a high prevalence of SDB.

  View details for DOI 10.1097/JGP.0b013e3181e446ea

  View details for Web of Science ID 000300642300002

  View details for PubMedID 20808112

• Citalopram for agitation in Alzheimer's disease: Design and methods ALZHEIMERS & DEMENTIA Drye, L. T., Ismail, Z., Porsteinsson, A. P., Rosenberg, P. B., Weintraub, D., Marano, C., Pelton, G., Frangakis, C., Rabins, P. V., Munro, C. A., Meinert, C. L., Devanand, D. P., Yesavage, J., Mintzer, J. E., Schneider, L. S., Pollock, B. G., Lyketsos, C. G. 2012; 8 (2): 121-130

  Abstract

  Agitation is one of the most common neuropsychiatric symptoms of Alzheimer's disease (AD), and is associated with serious adverse consequences for patients and caregivers. Evidence-supported treatment options for agitation are limited. The citalopram for agitation in Alzheimer's disease (CitAD) study was designed to evaluate the potential of citalopram to ameliorate these symptoms.CitAD is a randomized, double-masked, placebo-controlled multicenter clinical trial, with two parallel treatment groups assigned in a 1:1 ratio and randomization stratified by clinical center. The study included eight recruiting clinical centers, a chair's office, and a coordinating center located in university settings in the United States and Canada. A total of 200 individuals having probable AD with clinically significant agitation and without major depression were recruited for this study. Patients were randomized to receive citalopram (target dose of 30 mg/d) or matching placebo. Caregivers of patients in both treatment groups received a structured psychosocial therapy. Agitation was compared between treatment groups using the NeuroBehavioral Rating Scale and the AD Cooperative Study- Clinical Global Impression of Change, which are the primary outcomes. Functional performance, cognition, caregiver distress, and rates of adverse and serious adverse events were also measured.The authors believe the design elements in CitAD are important features to be included in trials assessing the safety and efficacy of psychotropic medications for clinically significant agitation in AD.

  View details for DOI 10.1016/j.jalz.2011.01.007

  View details for Web of Science ID 000301991600005

  View details for PubMedID 22301195

  View details for PubMedCentralID PMC3333484

• Phenotyping Apathy in Individuals With Alzheimer Disease Using Functional Principal Component Analysis. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Zeitzer, J. M., David, R., Friedman, L., Mulin, E., Garcia, R., Wang, J., Yesavage, J. A., Robert, P. H., Shannon, W. 2012

  Abstract

  OBJECTIVES:: To determine if there is a specific pattern of gross motor activity associated with apathy in individuals with Alzheimer disease (AD). DESIGN:: Examination of ad libitum 24-hour ambulatory gross motor activity patterns. SETTING:: Community-dwelling, outpatient. PARTICIPANTS:: Ninety-two individuals with AD, 35 of whom had apathy. MEASUREMENTS:: Wrist actigraphy data were collected and examined using functional principal component analysis (fPCA). RESULTS:: Individuals with apathy have a different pattern of gross motor activity than those without apathy (first fPCA component, p <0.0001, t = 5.73, df = 90, t test) such that there is a pronounced decline in early afternoon activity in those with apathy. This change in activity is independent of depression (p = 0.68, F[1, 89] = 0.05, analysis of variance). The decline in activity is consistent with an increase in napping. Those with apathy also have an early wake and bedtime (second fPCA component, t = 2.53, df = 90, p <0.05, t test). CONCLUSIONS:: There is a signature activity pattern in individuals with apathy and AD that is distinct from those without apathy and those with depression. Actigraphy may be a useful adjunctive measurement in the clinical diagnosis of apathy in the context of AD.

  View details for DOI 10.1097/JGP.0b013e318248779d

  View details for PubMedID 22367164

  View details for PubMedCentralID PMC3368995

• Delineating a Retesting Zone Using Receiver Operating Characteristic Analysis on Serial QuantiFERON Tuberculosis Test Results in US Healthcare Workers. Pulmonary medicine Thanassi, W., Noda, A., Hernandez, B., Newell, J., Terpeluk, P., Marder, D., Yesavage, J. A. 2012; 2012: 291294-?

  Abstract

  Objective. To find a statistically significant separation point for the QuantiFERON Gold In-Tube (QFT) interferon gamma release assay that could define an optimal "retesting zone" for use in serially tested low-risk populations who have test "reversions" from initially positive to subsequently negative results. Method. Using receiver operating characteristic analysis (ROC) to analyze retrospective data collected from 3 major hospitals, we searched for predictors of reversion until statistically significant separation points were revealed. A confirmatory regression analysis was performed on an additional sample. Results. In 575 initially positive US healthcare workers (HCWs), 300 (52.2%) had reversions, while 275 (47.8%) had two sequential positive tests. The most statistically significant (Kappa = 0.48, chi-square = 131.0, P < 0.001) separation point identified by the ROC for predicting reversion was the tuberculosis antigen minus-nil (TBag-nil) value at 1.11 International Units per milliliter (IU/mL). The second separation point was found at TBag-nil at 0.72 IU/mL (Kappa = 0.16, chi-square = 8.2, P < 0.01). The model was validated by the regression analysis of 287 HCWs. Conclusion. Reversion likelihood increases as the TBag-nil approaches the manufacturer's cut-point of 0.35 IU/mL. The most statistically significant separation point between those who test repeatedly positive and those who revert is 1.11 IU/mL. Clinicians should retest low-risk individuals with initial QFT results < 1.11 IU/mL.

  View details for DOI 10.1155/2012/291294

  View details for PubMedID 23326660

  View details for PubMedCentralID PMC3544373

• BDNF polymorphism predicts the rate of decline in skilled task performance and hippocampal volume in healthy individuals TRANSLATIONAL PSYCHIATRY Sanchez, M. M., Das, D., Taylor, J. L., Noda, A., Yesavage, J. A., Salehi, A. 2011; 1

  Abstract

  Numerous studies have indicated a link between the presence of polymorphism in brain-derived neurotrophic factor (BDNF) and cognitive and affective disorders. However, only a few have studied these effects longitudinally along with structural changes in the brain. This study was carried out to investigate whether valine-to-methionine substitution at position 66 (val66met) of pro-BDNF could be linked to alterations in the rate of decline in skilled task performance and structural changes in hippocampal volume. Participants consisted of 144 healthy Caucasian pilots (aged 40-69 years) who completed a minimum of 3 consecutive annual visits. Standardized flight simulator score (SFSS) was measured as a reliable and quantifiable indicator for skilled task performance. In addition, a subset of these individuals was assessed for hippocampal volume alterations using magnetic resonance imaging. We found that val66met substitution in BDNF correlated longitudinally with the rate of decline in SFSS. Structurally, age-dependent hippocampal volume changes were also significantly altered by this substitution. Our study suggests that val66met polymorphism in BDNF can be linked to the rate of decline in skilled task performance. Furthermore, this polymorphism could be used as a predictor of the effects of age on the structure of the hippocampus in healthy individuals. Such results have implications for understanding possible disabilities in older adults performing skilled tasks who are at a higher risk for cognitive and affective disorders.Translational Psychiatry (2011) 1, e51; doi:10.1038/tp.2011.47; published online 25 October 2011.

  View details for DOI 10.1038/tp.2011.47

  View details for Web of Science ID 000306216300008

  View details for PubMedID 22833197

• The Roles of COMT val158met Status and Aviation Expertise in Flight Simulator Performance and Cognitive Ability BEHAVIOR GENETICS Kennedy, Q., Taylor, J. L., Noda, A., Adamson, M., Murphy, G. M., Zeitzer, J. M., Yesavage, J. A. 2011; 41 (5): 700-708

  Abstract

  The polymorphic variation in the val158met position of the catechol-O-methyltransferase (COMT) gene is associated with differences in executive performance, processing speed, and attention. The purpose of this study is: (1) replicate previous COMT val158met findings on cognitive performance; (2) determine whether COMT val158met effects extend to a real-world task, aircraft navigation performance in a flight simulator; and (3) determine if aviation expertise moderates any effect of COMT val158met status on flight simulator performance. One hundred seventy two pilots aged 41-69 years, who varied in level of aviation training and experience, completed flight simulator, cognitive, and genetic assessments. Results indicate that although no COMT effect was found for an overall measure of flight performance, a positive effect of the met allele was detected for two aspects of cognitive ability: executive functioning and working memory performance. Pilots with the met/met genotype benefited more from increased levels of expertise than other participants on a traffic avoidance measure, which is a component of flight simulator performance. These preliminary results indicate that COMT val158met polymorphic variation can affect a real-world task.

  View details for DOI 10.1007/s10519-010-9436-z

  View details for Web of Science ID 000294297200008

  View details for PubMedID 21193954

  View details for PubMedCentralID PMC3163820

• Advanced techniques of sleep monitoring and genetic analyses in the study of cognitive problems of older adults Yesavage, J. CAMBRIDGE UNIV PRESS. 2011: S64

  View details for Web of Science ID 000300101100102

• Effectiveness of evening phototherapy for insomnia is reduced by bright daytime light exposure SLEEP MEDICINE Zeitzer, J. M., Friedman, L., Yesavage, J. A. 2011; 12 (8): 805-807

  Abstract

  To examine the effect of ambulatory daytime light exposure on phase delays and on the advances produced by timed exposure to bright evening or morning light.As a subset of a larger study, 32 older (63.0 ± 6.43 years) adults with primary insomnia were randomized to an at-home, single-blind, 12-week, parallel-group study entailing daily exposure to 45 min of scheduled evening or morning bright (∼4000 lux) light. Light exposure patterns during the baseline and the last week of treatment were monitored using actigraphs with built-in illuminance detectors. Circadian phase was determined through analysis of in-laboratory collected plasma melatonin.Less daytime light exposure during the last week of treatment was significantly associated with larger phase delays in response to evening light (r's>0.78). Less daytime light exposure during the last week of treatment was also associated with a significant delay in wake time (r's>-0.75). There were no such relationships between light exposure history and phase advances in response to morning light.Greater light exposure during the daytime may decrease the ability of evening light, but not morning light, exposure to engender meaningful changes of circadian phase.

  View details for DOI 10.1016/j.sleep.2011.02.005

  View details for Web of Science ID 000295764800013

  View details for PubMedID 21855408

  View details for PubMedCentralID PMC3176957

• Initial Cognitive Performance Predicts Longitudinal Aviator Performance JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES Yesavage, J. A., Jo, B., Adamson, M. M., Kennedy, Q., Noda, A., Hernandez, B., Zeitzer, J. M., Friedman, L. F., Fairchild, K., Scanlon, B. K., Murphy, G. M., Taylor, J. L. 2011; 66 (4): 444-453

  Abstract

  The goal of the study was to improve prediction of longitudinal flight simulator performance by studying cognitive factors that may moderate the influence of chronological age.We examined age-related change in aviation performance in aircraft pilots in relation to baseline cognitive ability measures and aviation expertise. Participants were aircraft pilots (N = 276) aged 40-77.9. Flight simulator performance and cognition were tested yearly; there were an average of 4.3 (± 2.7; range 1-13) data points per participant. Each participant was classified into one of the three levels of aviation expertise based on Federal Aviation Administration pilot proficiency ratings: least, moderate, or high expertise.Addition of measures of cognitive processing speed and executive function to a model of age-related change in aviation performance significantly improved the model. Processing speed and executive function performance interacted such that the slowest rate of decline in flight simulator performance was found in aviators with the highest scores on tests of these abilities. Expertise was beneficial to pilots across the age range studied; however, expertise did not show evidence of reducing the effect of age.These data suggest that longitudinal performance on an important real-world activity can be predicted by initial assessment of relevant cognitive abilities.

  View details for DOI 10.1093/geronb/gbr031

  View details for Web of Science ID 000293251900007

  View details for PubMedID 21586627

  View details for PubMedCentralID PMC3132267

• Circadian Clock Gene Polymorphisms and Sleep-Wake Disturbance in Alzheimer Disease AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Yesavage, J. A., Noda, A., Hernandez, B., Friedman, L., Cheng, J. J., Tinklenberg, J. R., Hallmayer, J., O'Hara, R., David, R., Robert, P., Landsverk, E., Zeitzer, J. M. 2011; 19 (7): 635-643

  Abstract

  One of the hypothesized causes of the breakdown in sleep-wake consolidation often occurring in individuals with Alzheimer disease (AD) is the dysfunction of the circadian clock. The goal of this study is to report indices of sleep-wake function collected from individuals with AD in relation to relevant polymorphisms in circadian clock-related genes.One week of ad libitum ambulatory sleep data collection.At-home collection of sleep data and in-laboratory questionnaire.Two cohorts of AD participants. Cohort 1 (N = 124): individuals with probable AD recruited from the Stanford/Veterans Affairs, National Institute on Aging Alzheimer's Disease Core Center (N = 81), and the Memory Disorders Clinic at the University of Nice School of Medicine (N = 43). Cohort 2 (N = 176): individuals with probable AD derived from the Alzheimer's Disease Neuroimaging Initiative data set.Determination of sleep-wake state was obtained by wrist actigraphy data for 7 days in Cohort 1 and by the Neuropsychiatric Inventory questionnaire for Cohort 2. Both cohorts were genotyped by using an Illumina Beadstation (Illumina, San Diego, CA), and 122 circadian-related single-nucleotide polymorphisms (SNPs) were examined. In Cohort 1, an additional polymorphism (variable-number tandem repeat in per3) was also determined.Adjusting for multiple tests, none of the candidate gene SNPs were significantly associated with the amount of wake time after sleep onset (WASO), a marker of sleep consolidation. Although the study was powered sufficiently to identify moderate-sized correlations, we found no relationships likely to be of clinical relevance.It is unlikely that a relationship with a clinically meaningful correlation exists between the circadian rhythm-associated SNPs and WASO in individuals with AD.

  View details for DOI 10.1097/JGP.0b013e31820d92b2

  View details for PubMedID 21709609

• Influences of APOE epsilon 4 and Expertise on Performance of Older Pilots PSYCHOLOGY AND AGING Taylor, J. L., Kennedy, Q., Adamson, M. M., Lazzeroni, L. C., Noda, A., Murphy, G. M., Yesavage, J. A. 2011; 26 (2): 480-487

  Abstract

  Little is known about how APOE ε4-related differences in cognitive performance translate to real-life performance, where training and experience may help to sustain performance. We investigated the influences of APOE ε4 status, expertise (FAA pilot proficiency ratings), and their interaction on longitudinal flight simulator performance. Over a 2-year period, 139 pilots aged 42-69 years were tested annually. APOE ε4 carriers had lower memory performance than noncarriers (p = .019). APOE interacted with Expertise (p = .036), such that the beneficial influence of expertise (p = .013) on longitudinal flight simulator performance was more pronounced for ε4 carriers. Results suggest that relevant training and activity may help sustain middle-aged and older adults' real-world performance, especially among APOE ε4 carriers.

  View details for DOI 10.1037/a0021697

  View details for Web of Science ID 000291668800026

  View details for PubMedID 21668123

  View details for PubMedCentralID PMC3117441

• Faster REM sleep EEG and worse restedness in older insomniacs with HLA DQB1*0602 PSYCHIATRY RESEARCH Zeitzer, J. M., Fisicaro, R. A., Grove, M. E., Mignot, E., Yesavage, J. A., Friedman, L. 2011; 187 (3): 397-400

  Abstract

  HLA DQB1*0602 is found in most individuals with hypocretin-deficient narcolepsy, a disorder characterized by a severe disruption of sleep and wake. Population studies indicate that DQB1*0602 may also be associated with normal phenotypic variation of rapid eye movement (REM) sleep. Disruption of REM sleep has been linked to specific symptoms of insomnia. We here examine the relationship of sleep and DQB1*0602 in older individuals (n=46) with primary insomnia, using objective (polysomnography, wrist actigraphy) and subjective (logs, scales) measures. DQB1*0602 positivity was similarly distributed in the older individuals with insomnia (24%) as in the general population (25%). Most sleep variables were statistically indistinguishable between DQB1*0602 positive and negative subjects except that those with the allele reported that they were significantly less well rested than those without it. When sleep efficiencies were lower than 70%, DQB1*0602 positive subjects reported being less well rested at the same sleep efficiency than those without the allele. Examination of EEG during REM sleep also revealed that DQB1*0602 positive subjects had EEG shifted towards faster frequencies compared with negative subjects. Thus, DQB1*0602 positivity is associated with both a shift in EEG power spectrum to faster frequencies during REM sleep and a diminution of restedness given the same sleep quantity.

  View details for DOI 10.1016/j.psychres.2011.01.007

  View details for Web of Science ID 000290506500014

  View details for PubMedID 21292329

  View details for PubMedCentralID PMC3079052

• Lack of Association Between COMT Polymorphisms and Apathy in Alzheimer's Disease JOURNAL OF ALZHEIMERS DISEASE David, R., Friedman, L., Mulin, E., Noda, A., Le Duff, F., Kennedy, Q., Garcia, R., Robert, P. H., Yesavage, J. A., Zeitzer, J. M. 2011; 27 (1): 155-161

  Abstract

  We tested the hypothesis that single nucleotide polymorphisms (SNPs) in catechol-O-methyltransferase (COMT) are associated with apathy in individuals with Alzheimer's disease (AD). We analyzed a cohort of 105 Caucasian individuals with AD (age = 79.3 ± 7.03 years; MMSE = 20.2 ± 4.4) according to the presence of apathy, as defined either by the Neuropsychiatric Inventory or the Apathy Inventory. Polymorphisms in seventeen SNPs in COMT were examined. A replication cohort consisting of 176 Caucasian AD subjects in the ADNI database was also analyzed. None of the candidate gene SNPs were significantly associated with the presence of apathy in either cohort. We did not find any SNPs in COMT that were consistently associated with apathy in individuals with AD.

  View details for DOI 10.3233/JAD-2011-110491

  View details for Web of Science ID 000296570400014

  View details for PubMedID 21785189

• Relationship between Apathy and Sleep Disturbance in Mild and Moderate Alzheimer's Disease: An Actigraphic Study JOURNAL OF ALZHEIMERS DISEASE Mulin, E., Zeitzer, J. M., Friedman, L., Le Duff, F., Yesavage, J., Robert, P. H., David, R. 2011; 25 (1): 85-91

  Abstract

  Apathy is the most frequently reported neuropsychiatric symptom across all stages of Alzheimer's disease (AD). Both apathy and sleep disorders are known to have independent negative effects on the quality of life in individuals with AD. The aim of this study was to assess the relationship between apathy and sleep/wake patterns in individuals with AD using ambulatory actigraphy. One hundred and three non-institutionalized individuals with AD wore a wrist actigraph continuously over seven consecutive 24-h periods. Apathy was assessed using the Neuropsychiatric Inventory. Daytime mean motor activity (dMMA) was calculated from daytime wrist actigraphy data. Actigraphic parameters of sleep included total sleep time (TST), wake after sleep onset (WASO), time in bed (TIB), WASO normalized by TIB, sleep latency, and nighttime mean motor activity (nMMA). Among the 103 individuals with AD (aged 76.9 ± 7.2 years; MMSE = 21.4 ± 4.3), those with apathy had significantly lower dMMA, higher WASO (both raw and normalized), and spent more time in bed during the night than those without apathy. Sleep latency, nMMA and TST did not differ significantly between the two subgroups. To our knowledge, this study is the first to identify a relationship between apathy and sleep disturbance in those with mild or moderate AD: apathy was associated with increased TIB during the night and more WASO. These results suggest that AD patients with apathy have less consolidated nocturnal sleep than those without apathy.

  View details for DOI 10.3233/JAD-2011-101701

  View details for Web of Science ID 000293377700009

  View details for PubMedID 21335662

• MR Spectroscopy for Assessment of Memantine Treatment in Mild to Moderate Alzheimer Dementia JOURNAL OF ALZHEIMERS DISEASE Ashford, J. W., Adamson, M., Beale, T., La, D., Hernandez, B., Noda, A., Rosen, A., O'Hara, R., Fairchild, J. K., Spielman, D., Yesavage, J. A. 2011; 26: 331-336

  Abstract

  Magnetic Resonance Spectroscopy (MRS) may provide a precise and reliable assessment of the extent and severity of neural tissue loss caused by various diseases. In particular, the N-Acetyl Aspartate (NAA) and Creatine (Cr) ratio has been found to be an indicator of the degree of neuronal loss in Alzheimer's disease (AD). Memantine is thought to benefit the AD brain by stabilizing the NMDA receptors on neurons in turn reducing excitotoxicity. Despite its effectiveness in treating moderate to severe AD, memantine has not had similar success in the treatment of mildly demented AD patients. The objective of this study was to test whether memantine would slow or prevent the loss of neurons in mild to moderate AD patients.A double-blind placebo-controlled study was designed to measure the effect of a year-long course of memantine in patients with a probable AD diagnosis with mild to moderate dementia. The primary outcome measure was stipulated to be change in MRS NAA/Cr ratio in inferior parietal cortex in memantine relative to the placebo treatment condition. The secondary outcome measures were changes in cognitive and function scale scores.This pilot study failed to demonstrate a benefit of memantine on the primary outcome measure, the inferior parietal NAA/Cr ratio, or the secondary outcome measures.More studies are needed to determine the effect of memantine on regions of the brain significantly affected by AD pathology.

  View details for DOI 10.3233/JAD-2011-0021

  View details for Web of Science ID 000297842800025

  View details for PubMedID 21971472

• Nicotine Deprivation and Pilot Performance During Simulated Flight AVIATION SPACE AND ENVIRONMENTAL MEDICINE Mumenthaler, M. S., Benowitz, N. L., Taylor, J. L., Friedman, L., Noda, A., Yesavage, J. A. 2010; 81 (7): 660-664

  Abstract

  Most airlines enforce no-smoking policies, potentially causing flight performance decrements in pilots who are smokers. We tested the hypotheses that nicotine withdrawal affects aircraft pilot performance within 12 h of smoking cessation and that chewing nicotine gum leads to significant relief of these withdrawal effects.There were 29 pilots, regular smokers, who were tested in a Frasca 141 flight simulator on two 13-h test days, each including three 75-min flights (0 hr, 6 hr, 12 hr) in a randomized, controlled trial. On the first day (baseline), all pilots smoked one cigarette per hour. On the second day, pilots were randomly assigned to one of four groups: (1) nicotine cigarettes; (2) nicotine gum; (3) placebo gum; (4) no cigarettes/no gum. Flight Summary Scores (FSS) were compared between groups with repeated measures ANOVAs.No statistically significant differences in overall simulator flight performance were revealed between pilots who smoked cigarettes and pilots who were not allowed to smoke cigarettes or chew nicotine gum, but there was a trend for pilots who were not allowed to smoke to perform worse. However, pilots who chewed placebo gum performed significantly worse during the 6-h (FSS = -0.03) as well as during the 12-h flight (FSS = -0.08) than pilots who chewed nicotine gum (FSS = 0.15 / 0.30, respectively).Results suggest that nicotine withdrawal effects can impair aircraft pilot performance within 12 h of smoking cessation and that during smoking abstinence chewing one stick of 4-mg nicotine gum per hour may lead to significantly better overall flight performance compared to chewing placebo gum.

  View details for DOI 10.3357/ASEM.2701.2010

  View details for Web of Science ID 000279187200006

  View details for PubMedID 20597245

• The impact of brain size on pilot performance varies with aviation training and years of education JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY Adamson, M. M., Samarina, V., Xu XiangYan, X. Y., Huynh, V., Kennedy, Q., Weiner, M., Yesavage, J., Taylor, J. L. 2010; 16 (3): 412-423

  Abstract

  Previous studies have consistently reported age-related changes in cognitive abilities and brain structure. Previous studies also suggest compensatory roles for specialized training, skill, and years of education in the age-related decline of cognitive function. The Stanford/VA Aviation Study examines the influence of specialized training and skill level (expertise) on age-related changes in cognition and brain structure. This preliminary report examines the effect of aviation expertise, years of education, age, and brain size on flight simulator performance in pilots aged 45-68 years. Fifty-one pilots were studied with structural magnetic resonance imaging, flight simulator, and processing speed tasks. There were significant main effects of age (p < .01) and expertise (p < .01), but not of whole brain size (p > .1) or education (p > .1), on flight simulator performance. However, even though age and brain size were correlated (r = -0.41), age differences in flight simulator performance were not explained by brain size. Both aviation expertise and education were involved in an interaction with brain size in predicting flight simulator performance (p < .05). These results point to the importance of examining measures of expertise and their interactions to assess age-related cognitive changes.

  View details for DOI 10.1017/S1355617710000111

  View details for Web of Science ID 000277579000002

  View details for PubMedID 20193103

  View details for PubMedCentralID PMC2862858

• Age and Expertise Effects in Aviation Decision Making and Flight Control in a Flight Simulator AVIATION SPACE AND ENVIRONMENTAL MEDICINE Kennedy, Q., Taylor, J. L., Reade, G., Yesavage, J. A. 2010; 81 (5): 489-497

  Abstract

  Age (due to declines in cognitive abilities necessary for navigation) and level of aviation expertise are two factors that may affect aviation performance and decision making under adverse weather conditions. We examined the roles of age, expertise, and their relationship on aviation decision making and flight control performance during a flight simulator task.Seventy-two IFR-rated general aviators, aged 19-79 yr, made multiple approach, holding pattern entry, and landing decisions while navigating under Instrument Flight Rules weather conditions. Over three trials in which the fog level varied, subjects decided whether or not to land the aircraft. They also completed two holding pattern entries. Subjects' flight control during approaches and holding patterns was measured.Older pilots (41+ yr) were more likely than younger pilots to land when visibility was inadequate (older pilots' mean false alarm rate: 0.44 vs 0.25). They also showed less precise flight control for components of the approach, performing 0.16 SD below mean approach scores. Expertise attenuated an age-related decline in flight control during holding patterns: older IFR/CFI performed 0.73 SD below mean score; younger IFR/CFI, younger CFII/ATP, older CFII/ATP: 0.32, 0.26, 0.03 SD above mean score. Additionally, pilots with faster processing speed (by median split) had a higher mean landing decision false alarm rate (0.42 vs 0.28), yet performed 0.14 SD above the mean approach control score.Results have implications regarding specialized training for older pilots and for understanding processes involved in older adults' real world decision making and performance.

  View details for DOI 10.3357/ASEM.2684.2010

  View details for Web of Science ID 000277133500006

  View details for PubMedID 20464816

  View details for PubMedCentralID PMC2905035

• Sleep and physical functioning in family caregivers of older adults with memory impairment INTERNATIONAL PSYCHOGERIATRICS Spira, A. P., Friedman, L., Beaudreau, S. A., Ancoli-Israel, S., Hernandez, B., Sheikh, J., Yesavage, J. 2010; 22 (2): 306-311

  Abstract

  Sleep disturbance is common in caregivers of older adults with memory disorders. Little is known, however, about the implications of caregivers' poor sleep with regard to their physical functioning.In this cross-sectional study, we investigated the association between objectively measured sleep and self-reported physical functioning in 45 caregivers (mean age = 68.6 years) who completed the Beck Depression Inventory-II, the Medical Outcomes Study SF-36, and the Mini-mental State Examination, and wore an actigraph for at least three days. Our primary predictors were actigraphic sleep parameters, and our outcome was the SF-36 Physical Functioning subscale.In multivariate-adjusted linear regression analyses, each 30-minute increase in caregivers' total sleep time was associated with a 2.2-point improvement in their Physical Functioning subscale scores (unstandardized regression coefficient (B) = 2.2, 95% confidence interval (CI) 1.0-3.4, p = 0.001). In addition, each 10-minute increase in time awake after initial sleep onset was associated with a 0.5-point decrease on the Physical Functioning subscale, although this was not statistically significant (B = -0.5, 95% CI -1.1, 0.1, p = 0.09).Our findings suggest that shorter sleep duration is associated with worse self-reported physical functioning in caregivers. Longitudinal studies are needed to determine whether poor sleep predicts functional decline in caregivers.

  View details for DOI 10.1017/S1041610209991153

  View details for Web of Science ID 000275132800016

  View details for PubMedID 19943990

  View details for PubMedCentralID PMC2822431

• Non-pharmacologic management of sleep disturbance in Alzheimer's disease JOURNAL OF NUTRITION HEALTH & AGING David, R., Zeitzer, J., Friedman, L., Noda, A., O'Hara, R., Robert, P., Yesavage, J. A. 2010; 14 (3): 203-206

  Abstract

  Sleep and wake in Alzheimer's disease (AD) are often fragmented as manifested by bouts of wakefulness at night and napping during the day. Management of sleep disturbances in AD is important because of their negative impact on both patients and caregivers. Pharmacological treatments, mainly sedative-hypnotics and antipsychotics, are often used but can be associated with significant adverse effects. Non-pharmacological treatments represent a beneficial alternative approach to the management of sleep disturbances in AD since they are associated with fewer adverse effects and their efficacy can be sustained after treatment has been completed. The aim of this article is to review non-pharmacological treatments, such as sleep hygiene, sleep restriction therapy (SRT), cognitive behavioral therapy (CBT), light therapy, and continuous positive airway pressure (CPAP), for the management of sleep/wake disturbances in AD.

  View details for DOI 10.1007/s12603-010-0050-9

  View details for Web of Science ID 000276527000006

  View details for PubMedID 20191254

• Increasing the Ranks of Academic Researchers in Mental Health: A Multisite Approach to Postdoctoral Fellowship Training ACADEMIC MEDICINE O'Hara, R., Cassidy-Eagle, E. L., Beaudreau, S. A., Eyler, L. T., Gray, H. L., Giese-Davis, J., Hubbard, J., Yesavage, J. A. 2010; 85 (1): 41-47

  Abstract

  This report highlights the use of multisite training for psychiatry and psychology postdoctoral fellows developing careers in academic clinical research in the field of mental health. The objective is to describe a model of training for young investigators to establish independent academic clinical research careers, including (1) program structure and eligibility, (2) program goals and development of a multisite curriculum, (3) use of technology for implementing the program across multiple sites, and (4) advantages and challenges of this multisite approach. In 2000, in collaboration with the Veterans Affairs (VA) Mental Illness Research, Education and Clinical Centers (MIRECCs), the VA Office of Academic Affiliations launched the Special Fellowship Program in Advanced Psychiatry and Psychology. Each of the 10 currently participating VA sites across the United States is affiliated with a MIRECC and an academic medical institution. In the first five years of this fellowship program, 83 fellows (34 psychiatrists and 49 psychologists) have participated. The success of this multisite approach is evidenced by the 58 fellows who have already graduated from the program: 70% have entered academic clinical research positions, and over 25 have obtained independent extramural grant support from the VA or the National Institutes of Health. Multisite training results in a greater transfer of knowledge and capitalizes on the nationwide availability of experts, creating unique networking and learning opportunities for trainees. The VA's multisite fellowship program plays a valuable role in preparing substantial numbers of psychiatry and psychology trainees for a range of academic clinical research and leadership positions in the field of mental health.

  View details for DOI 10.1097/ACM.0b013e3181c47c51

  View details for Web of Science ID 000276131300015

  View details for PubMedID 20042819

• Radiology corner. Case 41. Arcuate fasciculus damage seen on DTI in a blast-exposed soldier with mild traumatic brain injury (mTBI) with associated conduction aphasia. Military medicine Rosen, A., Zhang, Y., Zhan, W., Kasprisin, A., Martinson, S., Cheng, J., Weiner, M., Yesavage, J. A., Folio, L., Ashford, J. W. 2009; 174 (11): v-vi

  View details for PubMedID 19960837

• Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Britschgi, M., Olin, C. E., Johns, H. T., Takeda-Uchimura, Y., LeMieux, M. C., Rufibach, K., Rajadas, J., Zhang, H., Tomooka, B., Robinson, W. H., Clark, C. M., Fagan, A. M., Galasko, D. R., Holtzman, D. M., Jutel, M., Kaye, J. A., Lemere, C. A., Leszek, J., Li, G., Peskind, E. R., Quinn, J. F., Yesavage, J. A., Ghiso, J. A., Wyss-Coray, T. 2009; 106 (29): 12145-12150

  Abstract

  A number of distinct beta-amyloid (Abeta) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural Abeta-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic Abeta and amyloidogenic non-Abeta species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21-89 years. Antibody reactivity was most prominent against oligomeric assemblies of Abeta and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of Abeta1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant Abeta, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from Abeta toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with Abeta the monkeys developed high titers not only against Abeta peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of Abeta antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD.

  View details for DOI 10.1073/pnas.0904866106

  View details for Web of Science ID 000268178400059

  View details for PubMedID 19581601

  View details for PubMedCentralID PMC2715538

• Gene expression profile of the PDAPP mouse model for Alzheimer's disease with and without Apolipoprotein E NEUROBIOLOGY OF AGING Selwood, S. P., Parvathy, S., Cordell, B., Ryan, H. S., Oshidari, F., Vincent, V., Yesavage, J., Lazzeroni, L. C., Murphy, G. M. 2009; 30 (4): 574-590

  Abstract

  The APOE epsilon 4 allele is a strong risk factor for Alzheimer's disease (AD). However, the molecular basis for this effect remains unclear. We examined expression of approximately 12,000 genes and expressed sequence tags in the hippocampus and cortex of PDAPP (APP(V717)) mice modeling AD that show extensive amyloid beta (A beta) deposition, and in PDAPP mice lacking murine APOE expression, which show marked attenuation of A beta deposition in the brain. Wild type and APOE knockout animals were also examined. Expression levels were determined at the initial stage of A beta deposition, as well as in older animals showing extensive neuropathological changes. Fifty-four transcripts were identified using our statistical analysis as differentially regulated between the PDAPP and PDAPP/APOE ko mice, whereas 31 transcripts were classified as differentially regulated among PDAPP mice and WT animals, and seven transcripts were identified as regulated between the PDAPP/APOE ko animals and the APOE ko animals. Interestingly, many of the differentially regulated genes we detected can be related to biological processes previously shown to be important in AD pathophysiology, including inflammation, calcium homeostasis, cholesterol transport and uptake, kinases and phosphatases involved in tau phosphorylation and dephosphorylation, mitochondrial energy metabolism, protein degradation, neuronal growth, endoplasmic reticulum (ER) stress related proteins, antioxidant activity, cytoskeletal organization, and presenilin binding proteins. Regulated genes also included some not directly associated with AD in the past but likely to be involved in known AD pathophysiologic mechanisms, and others that may represent completely novel factors in the pathogenesis of AD. These results provide a global molecular profile of hippocampal and cortical gene expression during the initial and intermediate stages Abeta deposition, and the effects of APOE deletion on this process.

  View details for DOI 10.1016/j.neurobiolaging.2007.08.006

  View details for PubMedID 17904698

• HLA DQB1*0602 IS ASSOCIATED WITH SLEEP PERCEPTION IN OLDER INDIVIDUALS WITH INSOMNIA 23rd Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) Zeitzer, J., Grove, M. E., Mignot, E., Yesavage, J. A., Friedman, L. AMER ACAD SLEEP MEDICINE. 2009: A262–A262

  View details for Web of Science ID 000265542001152

• Clinical and Psychometric Validation of the Geriatric Depression Scale (GDS) for Portuguese Elders CLINICAL GERONTOLOGIST Pocinho, M. T., Farate, C., Dias, C. A., Lee, T. T., Yesavage, J. A. 2009; 32 (2): 223-236

  View details for DOI 10.1080/07317110802678680

  View details for Web of Science ID 000283865400008

• Neuropsychiatric diagnosis and management of chronic sequelae of war-related mild to moderate traumatic brain injury JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT Halbauer, J. D., Ashford, J. W., Zeitzer, J. M., Adamson, M. M., Lew, H. L., Yesavage, J. A. 2009; 46 (6): 757-795

  Abstract

  Soldiers with a traumatic brain injury (TBI) present with an array of neuropsychiatric symptoms that can be grouped into nosological clusters: (1) cognitive dysfunctions: difficulties in memory, attention, language, visuospatial cognition, sensory-motor integration, affect recognition, and/or executive function typically associated with neocortical damage; (2) neurobehavioral disorders: mood, affect, anxiety, posttraumatic stress, and psychosis, as well as agitation, sleep problems, and libido loss, that may have been caused by damage to the cortex, limbic system, and/or brain stem monoaminergic projection systems; (3) somatosensory disruptions: impaired smell, vision, hearing, equilibrium, taste, and somatosensory perception frequently caused by trauma to the sensory organs or their projections through the brain stem to central processing systems; (4) somatic symptoms: headache and chronic pain; and (5) substance dependence. TBI-related cognitive impairment is common in veterans who have served in recent conflicts in the Middle East and is often related to blasts from improvised explosive devices. Although neurobehavioral disorders such as depression and posttraumatic stress disorder commonly occur after combat, the presentation of such disorders in those with head injury may pass undetected with use of current diagnostic criteria and neuropsychological instruments. With a multidimensional approach (such as the biopsychosocial model) applied to each symptom cluster, psychological, occupational, and social dysfunction can be delineated and managed.

  View details for DOI 10.1682/JRRD.2008.08.0119

  View details for Web of Science ID 000272638100010

  View details for PubMedID 20104402

• Acetylcholinesterase inhibitor in combination with cognitive training in older adults JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES Yesavage, J. A., Friedman, L., Ashford, J. W., Kraemer, H. C., Mumenthaler, M. S., Noda, A., Hoblyn, J. 2008; 63 (5): P288-P294

  Abstract

  To determine if donepezil, an acetylcholinesterase (AChE) inhibitor, improved the assimilation of cognitive training by older adults with memory complaints, we gave 168 nondemented, community-dwelling volunteers with memory complaints either 5 mg of donepezil (Aricept) or placebo daily for 6 weeks in a randomized, double-blind, placebo-controlled trial. The dosage rose to 10 mg daily for another 6 weeks before a 2-week course of cognitive training and was maintained for the remainder of a year. Cognitive training improved performance; donepezil was well tolerated. However, there were no significant benefits of donepezil compared with placebo. An additional dose-ranging study with a starting dose of 5 mg a day suggests that the high dose was not the reason. Physiological tolerance may occur with chronic donepezil treatment and may increase AChE levels; this may be why short-term studies have shown the benefit of AChE inhibitor use in nondemented participants whereas chronic use has failed to enhance cognition.

  View details for Web of Science ID 000259517200004

  View details for PubMedID 18818443

• Subclinical anxiety symptoms, sleep, and daytime dysfunction in older adults with primary insomnia JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Spira, A. P., Friedman, L., Aulakh, J. S., Lee, T., Sheikh, J. I., Yesavage, J. A. 2008; 21 (2): 149-153

  Abstract

  Both insomnia complaints and anxiety disorders are common in older adults, and are associated with poor daytime functioning. The present study investigated whether subclinical levels of anxiety were associated with sleep disturbance and daytime functioning in older adults who met diagnostic criteria for primary insomnia, and therefore did not meet criteria for depression or an anxiety disorder. After adjustment for depressive symptoms, elevated state anxiety was associated with higher levels of wake after sleep onset (measured by both actigraphy and sleep log) and shorter sleep onset latency (measured by sleep log). Higher levels of trait anxiety were associated with greater wake after sleep onset (measured by sleep log). Elevated state and trait anxiety were associated with worse social functioning, and higher levels of trait anxiety were associated with worse role functioning. Thus, subclinical anxiety symptoms may be an important target for clinical intervention to improve sleep and functioning in older adults with primary insomnia.

  View details for DOI 10.1177/0891988707317120

  View details for Web of Science ID 000256077800008

  View details for PubMedID 18474724

• Subclinical anxiety symptoms, sleep, and daytime dysfunction in older adults with primary insomnia 20th Annual Meeting of the Associated-Professional-Sleep-Societies Spira, A. P., Friedman, L., Aulakh, J. S., Lee, T., Sheikh, J. I., Yesavage, J. A. SAGE PUBLICATIONS INC. 2008: 56–60

  Abstract

  "Both Insomnia complaints and anxiety-related distress are common in older adults, and are associated with poor daytime functioning. We investigated whether subclinical levels of anxiety were associated with sleep disturbance and daytime functioning in older adults who met diagnostic criteria for primary insomnia, and therefore but did not meet criteria for depression or an anxiety disorder. After adjustment for depressive symptoms, elevated state anxiety was associated with higher levels of wake after sleep onset (measured by both actigraphy and sleep log) and shorter sleep sleep onset latency (measured by sleep log). Higher levels of trait anxiety were associated with greater wake after sleep onset (measured by sleep log). Elevated state and trait anxiety were associated with worse and social functioning, and higher levels of trait anxiety were associated with worse role functioning. Thus, subclinical anxiety symptoms may be an important target for clinical intervention to improve sleep and functioning in older adults with primary insomnia."

  View details for DOI 10.1177/0891988707311043

  View details for Web of Science ID 000253457700008

  View details for PubMedID 18287171

• Overlap of mild TBI and mental health conditions in returning OIF/OEF service members and veterans JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT Lew, H. L., Vanderploeg, R. D., Moore, D. E., Schwab, K., Friedman, L., Yesavage, J., Keane, T. M., Warden, D. L., Sigford, B. J. 2008; 45 (3): XI-XVI

  View details for DOI 10.1682/JRRD.2008.05.0064

  View details for Web of Science ID 000257230300002

  View details for PubMedID 18629743

• Donepezil treatment and Alzheimer disease: Can the results of Randomized clinical trials be applied to Alzheimer disease patients in clinical practice? 10th International Conference on Alzheimers Disease and Related Disorders Tinklenberg, J. R., Kraemer, H. C., Yaffe, K., Ross, L., Sheikh, J., Ashford, J. W., Yesavage, J. A., Taylor, J. L. LIPPINCOTT WILLIAMS & WILKINS. 2007: 953–60

  Abstract

  To determine if results from randomized clinical trials of donepezil in Alzheimer disease (AD) patients can be applied to AD patients in clinical practice by comparing the findings from a Nordic one-year randomized AD donepezil trial with data from a one-year prospective, observational study of AD patients.AD patients from a consortium of California sites were systematically followed for at least one year. Their treatment regimens, including prescription of donepezil, were determined by their individual physician according to his or her usual criteria.The 148 California patients treated with donepezil had a one-year decline of 1.3 (3.5 SD) points on the Mini-Mental State Exam compared to a decline of 3.3 (4.4 SD) in the 158 AD patients who received no anti-Alzheimer drugs. The Mini-Mental State Exam decline in Nordic sample was approximately 0.25 points for the 91 patients receiving donepezil and approximately 2.2 for the 98 placebo patients. The overall effect sizes were estimated at about 0.49 in both studies. The California data were further analyzed using propensity methods; after taking into account differences that could bias prescribing decisions, benefits associated with taking donepezil remained.A comparison of a randomized clinical trial of donepezil in AD patients and this observational study indicates that if appropriate methodological and statistical precautions are undertaken, then results from randomized clinical trials can be predictive with AD patients in clinical practice. This California study supports the modest effectiveness of donepezil in AD patients having clinical characteristics similar to those of the Nordic study.

  View details for Web of Science ID 000250617800005

  View details for PubMedID 17974866

• Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins NATURE MEDICINE Ray, S., Britschgi, M., Herbert, C., Takeda-Uchimura, Y., Boxer, A., Blennow, K., Friedman, L. F., Galasko, D. R., Jutel, M., Karydas, A., Kaye, J. A., Leszek, J., Miller, B. L., Minthon, L., Quinn, J. F., Rabinovici, G. D., Robinson, W. H., Sabbagh, M. N., So, Y. T., Sparks, D. L., Tabaton, M., Tinklenberg, J., Yesavage, J. A., Tibshirani, R., Wyss-Coray, T. 2007; 13 (11): 1359-1362

  Abstract

  A molecular test for Alzheimer's disease could lead to better treatment and therapies. We found 18 signaling proteins in blood plasma that can be used to classify blinded samples from Alzheimer's and control subjects with close to 90% accuracy and to identify patients who had mild cognitive impairment that progressed to Alzheimer's disease 2-6 years later. Biological analysis of the 18 proteins points to systemic dysregulation of hematopoiesis, immune responses, apoptosis and neuronal support in presymptomatic Alzheimer's disease.

  View details for DOI 10.1038/nm1653

  View details for Web of Science ID 000250736900029

  View details for PubMedID 17934472

• Should one use medications in combination with cognitive training? If so, which ones? JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES Yesavage, J., Hoblyn, J., Friedman, L., Mumenthaler, M., Schneider, B., O'Hara, R. 2007; 62: 11-18

  Abstract

  In this article, we review current research regarding diagnosis of cognitive impairment in nondemented adults and discuss why medications and cognitive training together may be more beneficial than either alone. We also review potential cognitive enhancers and future research challenges. There are major reasons for such research: (a) Large numbers of older adults without dementia but with cognitive problems are not treatable with current cognitive training techniques; (b) some medications offer a rationale (i.e., cognitive enhancement) and some evidence that they might be a useful adjunct; and (c) there are unanswered questions about which population to target, which medications to use, how to administer them, and issues regarding tolerance and use of appropriate (active) placebo controls. As the number of cognitively impaired older adults grows, it is likely that there will be pressure to treat more broadly with both medications and cognitive training.

  View details for Web of Science ID 000253836500002

  View details for PubMedID 17565161

• Statistical and pharmacoeconomic issues for Alzheimer's screening ALZHEIMERS & DEMENTIA Ashford, J. W., Kraemer, H. C., Tinklenberg, J. R., O'Hara, R., Taylor, J. L., Yesavage, J. A. 2007; 3 (2): 126-126

  View details for DOI 10.1016/j.jalz.2007.03.004

  View details for Web of Science ID 000249579900008

  View details for PubMedID 19595924

• In Alzheimer disease, increased wake fragmentation found in those with lower hypocretin-1 NEUROLOGY Friedman, L. F., Zeitzer, J. M., Lin, L., Hoff, D., Mignot, E., Peskind, E. R., Yesavage, J. A. 2007; 68 (10): 793-794

  View details for Web of Science ID 000244679900020

  View details for PubMedID 17339595

• Pilot age and expertise predict flight simulator performance - A 3-year longitudinal study NEUROLOGY Taylor, J. L., Kennedy, Q., Noda, A., Yesavage, J. A. 2007; 68 (9): 648-654

  Abstract

  Expert knowledge may compensate for age-related declines in basic cognitive and sensory-motor abilities in some skill domains. We investigated the influence of age and aviation expertise (indexed by Federal Aviation Administration pilot ratings) on longitudinal flight simulator performance.Over a 3-year period, 118 general aviation pilots aged 40 to 69 years were tested annually, in which their flight performance was scored in terms of 1) executing air-traffic controller communications; 2) traffic avoidance; 3) scanning cockpit instruments; 4) executing an approach to landing; and 5) a flight summary score.More expert pilots had better flight summary scores at baseline and showed less decline over time. Secondary analyses revealed that expertise effects were most evident in the accuracy of executing aviation communications, the measure on which performance declined most sharply over time. Regarding age, even though older pilots initially performed worse than younger pilots, over time older pilots showed less decline in flight summary scores than younger pilots. Secondary analyses revealed that the oldest pilots did well over time because their traffic avoidance performance improved more vs younger pilots.These longitudinal findings support previous cross-sectional studies in aviation as well as non-aviation domains, which demonstrated the advantageous effect of prior experience and specialized expertise on older adults' skilled cognitive performances.

  View details for Web of Science ID 000244482400005

  View details for PubMedID 17325270

  View details for PubMedCentralID PMC2907140

• Hypocretin-1 is inversely associated with wake fragmentation in Alzheimer's disease 21st Annual Meeting of the American-Professional-Sleep-Societies Zeitzer, J., Friedman, L., Lin, L., Mignot, E., Peskind, E., Yesavage, J. AMER ACAD SLEEP MEDICINE. 2007: A302–A302

  View details for Web of Science ID 000246224900882

• Coping, symptoms, and functioning outcomes of patients with posttraumatic stress disorder JOURNAL OF TRAUMATIC STRESS Tiet, Q. Q., Rosen, C., Cavella, S., Moos, R. H., Finney, J. W., Yesavage, J. 2006; 19 (6): 799-811

  Abstract

  This study examines the association between approach coping and better functioning outcomes and the reciprocal relationships between coping and posttraumatic stress disorder (PTSD) symptoms in patients diagnosed with PTSD. Posttraumatic stress disorder patients receiving services in five VA health care systems were randomly selected and surveyed at baseline and followed 10 months later. Analyses of longitudinal data using structural equation modeling techniques showed that more approach coping predicted better family and social functioning. Cognitive avoidance coping predicted more PTSD symptoms, and more PTSD symptoms predicted more approach coping and more behavioral avoidance coping. Approach coping may enable patients with chronic PTSD to establish and maintain better relationships with family and friends, despite continuing PTSD.

  View details for DOI 10.1002/jts.20185

  View details for Web of Science ID 000243184200005

  View details for PubMedID 17195979

• No improvement of posttraumatic stress disorder symptoms with guanfacine treatment AMERICAN JOURNAL OF PSYCHIATRY Neylan, T. C., Lenoci, M., Samuelson, K. W., Metzler, T. J., Henn-Haase, C., Hierholzer, R. W., Lindley, S. E., Otte, C., Schoenfeld, F. B., Yesavage, J. A., Marmar, C. R. 2006; 163 (12): 2186-2188

  Abstract

  The authors report an 8-week, double-blind, randomized controlled trial of guanfacine versus placebo for posttraumatic stress disorder (PTSD).Veterans with chronic PTSD who were medication-free or receiving stable pharmacotherapy were randomly assigned to guanfacine (N=29) versus placebo (N=34).Guanfacine had no effect on PTSD symptoms, subjective sleep quality, or general mood disturbances. Guanfacine was associated with a number of side effects.These results do not support the use of alpha 2 agonists in veterans with chronic PTSD.

  View details for Web of Science ID 000242626000029

  View details for PubMedID 17151174

• The Cost-Time Index: A new method for measuring the efficiencies of recruitment-resources in clinical trials CONTEMPORARY CLINICAL TRIALS Ota, K. S., Friedman, L., Ashford, J. W., Hernandez, B., Penner, A. L., Stepp, A. M., Raam, R., Yesavage, J. A. 2006; 27 (6): 494-497

  Abstract

  Paid media are important resources used to recruit subjects in clinical trials. An index for evaluating which advertising resource has minimal cost and time requirement for patient accrual, for a given study design, has not been previously introduced. In this communication the authors present a new index, the Cost-Time Index, which represents a measure of the average amount of money and time spent, simultaneously, on a given advertising resource to recruit one analyzable subject. This index can be calculated using retrospective data and may be a useful tool for comparing recruitment efficiencies among various resources. The authors demonstrate the utility of the Cost-Time Index and recommend its use as an additional variable in future studies regarding recruitment strategies in clinical trials.

  View details for DOI 10.1016/j.cct.2006.05.008

  View details for Web of Science ID 000242790000002

  View details for PubMedID 16820328

• Factors associated with psychiatric hospitalization of individuals diagnosed with dementia and comorbid bipolar disorder JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Brooks, J. O., Hoblyn, J. C., Kraemer, H. C., Yesavage, J. A. 2006; 19 (2): 72-77

  Abstract

  The objective was to determine risk factors of psychiatric hospitalization among a Veterans Administration database of patients with dementia and comorbid bipolar disorder (D+BD). Patients with D+BD had a greater prevalence of psychiatric hospitalization (28% vs 4%). The strongest predictor of psychiatric hospitalization was the presence of an alcohol use disorder (51% risk); patients without alcohol use disorders but under the age of 70 had the next highest risk (33% risk). However, patients with an alcohol use disorder had shorter psychiatric hospitalizations than those without. Compared with patients without BD, D+BD patients were more likely to have alcohol use disorders (15% vs 3%) and any other substance use problem (10% vs 1%). In patients diagnosed with dementia and bipolar disorder, the strongest risk factor for psychiatric hospitalization was an alcohol abuse disorder. These findings suggest that disorders with increased frequency in BD affect the course of dementia.

  View details for DOI 10.1177/0891988706286215

  View details for Web of Science ID 000237778800003

  View details for PubMedID 16690991

• Caution regarding the use of pilot studies to guide power calculations for study proposals ARCHIVES OF GENERAL PSYCHIATRY Kraemer, H. C., Mintz, J., Noda, A., Tinklenberg, J., Yesavage, J. A. 2006; 63 (5): 484-489

  Abstract

  Clinical researchers often propose (or review committees demand) pilot studies to determine whether a study is worth performing and to guide power calculations. The most likely outcomes are that (1) studies worth performing are aborted and (2) studies that are not aborted are underpowered. There are many excellent reasons for performing pilot studies. The argument herein is not meant to discourage clinical researchers from performing pilot studies (or review committees from requiring them) but simply to caution against their use for the objective of guiding power calculations.

  View details for Web of Science ID 000237215800002

  View details for PubMedID 16651505

• The brain-derived neurotrophic factor Val66Met polymorphism and rate of decline in Alzheimer's disease JOURNAL OF ALZHEIMERS DISEASE Chuu, J. Y., Taylor, J. L., Tinklenberg, J., Noda, A., Yesavage, J., Murphy, G. M. 2006; 9 (1): 43-49

  Abstract

  It is largely unknown why some patients with Alzheimer's disease (AD) decline cognitively more rapidly than others. Genetic differences among patients could influence rate of decline. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in the survival neurons and in memory function. BDNF levels are reduced in the brain in AD. The Val66Met polymorphism in the BDNF gene modifies neuronal BDNF secretion, and affects hippocampal function and memory performance. We tested the hypothesis that the BDNF Val66Met polymorphism influences rate of cognitive decline in AD. In a sample of 149 AD patients followed for an average of 3.9 years, we found no effect of BDNF Val66Met genotype on rate of change in the Mini Mental State Examination. Results were similar when we excluded patients taking an acetylcholinesterase inhibitor, those placed in a nursing home during the study, or those with a neuropathological diagnosis that included AD plus an entity other than AD. We also found no evidence that the effects of the BDNF Val66Met genotype depend on APOE genotype, which itself had no effect on rate of cognitive change. These findings suggest that the functional BDNF Val66Met variant is not a major determinant of rate of cognitive decline in AD.

  View details for Web of Science ID 000237795900004

  View details for PubMedID 16627933

• Factors in choosing atypical antipsychotics: Toward understanding the bases of physicians' prescribing decisions JOURNAL OF PSYCHIATRIC RESEARCH Hoblyn, J., Noda, A., Yesavage, J. A., Brooks, J. O., Sheikh, J., Lee, T., Tinklenberg, J. R., Schneider, B., O'Hara, R., Leslie, D. L., Rosenheck, R. A., Kraemer, H. C. 2006; 40 (2): 160-166

  Abstract

  Off-label prescribing of medications, polypharmacy, and other questionable prescribing practices have led investigators to examine a large VA pharmacy database to determine if physician prescribing decisions appear reasonable.The current study addresses the question of physician prescribing of atypical antipsychotics in 34,925 veterans with schizophrenia, using a series of signal detection analyses.These results suggest that only three factors (hospital size, age, and secondary diagnosis) allow classification of patients prescribed atypicals into three groups with frequencies of use of atypicals ranging from 43% to 79%, and that these results are consistent with reasonable clinical practice.Results of two-stage signal detection analyses are readily interpretable by clinicians and administrators who are faced with the task of evaluating how physicians prescribe medications in clinical practice. Physicians' decisions to prescribe atypical antipsychotics are based on both patient and fiscal considerations. This likely reflects a combination of clinical judgment and institutional guidelines.

  View details for DOI 10.1016/j.jpsychires.2005.06.004

  View details for Web of Science ID 000235641200009

  View details for PubMedID 16150458

• Perspectives on depression, mild cognitive impairment, and cognitive decline ARCHIVES OF GENERAL PSYCHIATRY Steffens, D. C., Otey, E., Alexopoulos, G. S., Butters, M. A., Cuthbert, B., Ganguli, M., Geda, Y. E., Hendrie, H. C., Krishnan, R. R., Kumar, A., Lopez, O. L., Lyketsos, C. G., Mast, B. T., Morris, J. C., Norton, M. C., Peavy, G. M., PETERSEN, R. C., Reynolds, C. F., Salloway, S., Welsh-Bohmer, K. A., Yesavage, J. 2006; 63 (2): 130-138

  Abstract

  The public health implications of depression and cognitive impairment in late life are enormous. Cognitive impairment and late-life depression are associated with increased risk for subsequent dementia; however, investigations of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND DATA SOURCE: The National Institute of Mental Health organized the conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to consider how the varied perspectives might be better integrated to examine the associations among depression, mild cognitive impairment, and cognitive decline and to illuminate the common or distinct mechanisms involved in these associations.The following 2 broad questions were addressed: (1) What gaps in our knowledge have the greatest public health significance? (2) Can we more efficiently use our research dollars and participant resources to fill these gaps? Meeting participants included grantees from the National Institute of Mental Health and the National Institute on Aging and program staff from the National Institute of Mental Health, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke.One of the most important recommendations to emerge from the meeting discussions is for increased collaboration among clinical and epidemiological investigators whose work focuses in the area of depression with those working primarily in the area of memory disorders. Directions for future research were identified.

  View details for Web of Science ID 000235150900003

  View details for PubMedID 16461855

• Hormone replacement therapy and longitudinal cognitive performance in postmenopausal women AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY O'Hara, R., Schroder, C. M., Bloss, C., Bailey, A. M., Alyeshmerni, A. M., Mumenthaler, M. S., Friedman, L. F., Yesavage, J. A. 2005; 13 (12): 1107-1110

  Abstract

  The authors examined the impact of hormone replacement therapy (HRT) on longitudinal cognitive performance (controlling for mood state) in 69 community-dwelling, postmenopausal women.The authors conducted a 5-year follow-up of cognitive performance in 37 postmenopausal HRT users and 32 non-users. The groups did not differ with respect to age, years of education, or inter-test interval.No main effect of HRT was observed on any of the cognitive measures, and depressive symptomatology did not affect the relationship between HRT and cognition.Overall, our findings do not suggest that HRT affects longitudinal cognitive performance in postmenopausal, community-dwelling older women.

  View details for Web of Science ID 000233614500011

  View details for PubMedID 16319304

• Nocturnal sleep apnea/hypopnea is associated with lower memory performance in APOE epsilon 4 carriers NEUROLOGY O'Hara, R., Schroder, C. M., Kraemer, H. C., Kryla, N., Cao, C., Miller, E., Schatzberg, A. F., Yesavage, J. A., Murphy, G. M. 2005; 65 (4): 642-644

  Abstract

  The authors investigated the relationship between obstructive sleep apnea/hypopnea (OSAH) and cognition in 36 older adults, 18 APOE epsilon4 carriers, and 18 non-carriers. Greater numbers of respiratory events negatively impacted memory function in epsilon4 carriers only. This is the first study to provide preliminary evidence for a negative interaction of APOE epsilon4 and OSAH on memory in older adults, which may have important implications for treating cognitive decline and delaying dementia onset.

  View details for Web of Science ID 000231371600035

  View details for PubMedID 16116137

• Relating medial temporal lobe volume to frontal fMRI activation for memory encoding in older adults CORTEX Rosen, A. C., Gabrieli, J. D., Stoub, T., Prull, M. W., O'Hara, R., Yesavage, J., DeToledo-Morrell, L. 2005; 41 (4): 595-602

  Abstract

  Neuroimaging research on the brain basis of memory decline in older adults typically has examined age-related changes either in structure or in function. Structural imaging studies have found that smaller medial temporal lobe (MTL) volumes are associated with lower memory performance. Functional imaging studies have found that older adults often exhibit bilateral frontal-lobe activation under conditions where young adults exhibit unilateral frontal activation. As yet, no one has examined whether these MTL structural and frontal-lobe functional findings are associated. In this study, we tested whether these findings were correlated in a population of healthy older adults in whom we previously demonstrated verbal memory performance was positively associated with left entorhinal cortex volume in the MTL (Rosen et al., 2003) and right frontal lobe activation during memory encoding (Rosen et al., 2002). Thirteen, non-demented, community-dwelling older adults participated both in a functional MRI (fMRI) study of verbal memory encoding and structural imaging. MRI-derived left entorhinal volume was measured on structural images and entered as a regressor against fMRI activation during verbal memory encoding. Right frontal activation (Brodmann's Area 47/insula) was positively correlated with left entorhinal cortex volume. These findings indicate a positive association between MTL volume and right frontal-lobe function that may underlie variability in memory performance among the elderly, and also suggest a two-stage model of memory decline in aging.

  View details for Web of Science ID 000230574200015

  View details for PubMedID 16042035

• Tolerability and effectiveness of lamotrigine in complex elderly patients JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Aulakh, J. S., Hawkins, J. W., Athwal, H. S., Sheikh, J. I., Yesavage, J., Tinklenberg, J. R. 2005; 18 (1): 8-11

  Abstract

  There is paucity of medical literature on the use of lamotrigine in elderly patients who have behavior problems and diverse psychiatric syndromes. This article is a retrospective case series summarizing the authors' experience with this medication. In a 20-patient case series from an institutional review board-approved retrospective chart review, the tolerability and efficacy of lamotrigine was evaluated for the management of agitated and aggressive behaviors in nursing home patients with a range of psychiatric and medical diagnoses. Nineteen of the elderly nursing home patients tolerated lamotrigine treatment, and 18 showed modest clinical improvement. These results support the authors' belief that controlled clinical investigations of this medication should be performed.

  View details for DOI 10.1177/0891988704271762

  View details for Web of Science ID 000226923100002

  View details for PubMedID 15681622

• Cognitive ability, expertise, and age differences in following air-traffic control instructions 9th Biennial Cognitive Aging Conference Taylor, J. L., O'Hara, R., Mumenthaler, M. S., Rosen, A. C., Yesavage, J. A. AMER PSYCHOLOGICAL ASSOC. 2005: 117–33

  Abstract

  Differences in cognitive ability and domain-specific expertise may help explain age differences in pilot performance. Pilots heard air-traffic controller messages and then executed them while "flying" in a simulator. Messages varied in length and speech rate. Age was associated with lower accuracy, but the expected Age x Message Difficulty interactions were not obtained. Expertise, as indexed by pilot ratings, was associated with higher accuracy; yet expertise did not reduce age differences in accuracy. The effect of age on communication task accuracy was largely explainable as an age-associated decrease in working memory span, which in turn was explainable as decreases in both speed and interference control. Results are discussed within frameworks of deliberate practice and cognitive mediation of age differences.

  View details for DOI 10.1037/0882-7974.20.1.117

  View details for Web of Science ID 000227731300009

  View details for PubMedID 15769218

• The development and initial validation of the Terminally Ill Grief or Depression Scale (TIGDS) INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH Periyakoil, V. S., Kraemer, H. C., Noda, A., Moos, R., Hallenbeck, J., Webster, M., Yesavage, J. A. 2005; 14 (4): 202-212

  Abstract

  Patients often experience 'preparatory-grief' as they cope with the dying process. Some may be depressed. The Terminally Ill Grief or Depression Scale (TIGDS), comprising grief and depression sub-scales, is a new self-report measure designed to differentiate between preparatory-grief and depression in adult inpatients. The initial 100-item inventory was assembled based on literature review, interviews with clinicians and dying patients and then shortened to 42 items based on consensus expert opinion. Validity and reliability were tested in a sample of 55 terminally ill adults. The consensus clinical opinion was used as the gold standard to differentiate between preparatory grief and depression. The intra-class correlation coefficient was high (it was calculated to estimate the test-retest reliability for the 47 patients who had completed the TIGDS twice--retest was administered 2 to 7 days after the initial test), ranging from 0.86 (grief) to 0.97 (depression). The validity of TIGDS was assessed using a receiver operating characteristic curve analysis, comparing the first test with the clinical criterion. The first and only variable and cut-point was the depression score (chi-square = 18.4, p < 0.001, cut point = 3). The sensitivity of the TIGDS was 0.727 and specificity was 0.886 for the depression = 3 cutoff score. The construct validity of the TIGDS was tested by comparing with the Hospital Anxiety and Depression Scale (HADS). The TIGDS depression subscale showed strong convergent validity and the TIGDS grief subscale showed strong discriminant validity with the HADS total score.

  View details for DOI 10.1002/mpr.8

  View details for Web of Science ID 000234094000003

  View details for PubMedID 16395873

• Sleep apnea/hypopnea is associated with lower memory performance in APOE epsilon 4 allele carriers only 19th Annual Meeting of the Associated-Professional-Sleep-Societies O'Hara, R. M., Schroder, C. M., Kraemer, H. C., Kryla, N. R., Cao, C., Miller, E. H., Schatzberg, A. F., Yesavage, J. A., Murphy, G. M. AMER ACAD SLEEP MEDICINE. 2005: A109–A109

  View details for Web of Science ID 000228906100322

• Sleep and circadian abnormalities in a transgenic mouse model of Alzheimer's disease: A role for cholinergic transmission NEUROSCIENCE Wisor, J. P., Edgar, D. M., Yesavage, J., Ryan, H. S., McCormick, C. M., Lapustea, N., Murphy, G. M. 2005; 131 (2): 375-385

  Abstract

  The Tg2576 mouse model of Alzheimer's disease (AD) exhibits age-dependent amyloid beta (Abeta) deposition in the brain. We studied electroencephalographically defined sleep and the circadian regulation of waking activities in Tg2576 mice to determine whether these animals exhibit sleep abnormalities akin to those in AD. In Tg2576 mice at all ages studied, the circadian period of wheel running rhythms in constant darkness was significantly longer than that of wild type mice. In addition, the increase in electroencephalographic delta (1-4 Hz) power that occurs during non-rapid eye movement sleep after sleep deprivation was blunted in Tg2576 mice relative to controls at all ages studied. Electroencephalographic power during non-rapid eye movement sleep was shifted to higher frequencies in plaque-bearing mice relative to controls. The wake-promoting efficacy of the acetylcholinesterase inhibitor donepezil was lower in plaque-bearing Tg2576 mice than in controls. Sleep abnormalities in Tg2576 mice may be due in part to a cholinergic deficit in these mice. At 22 months of age, two additional deficits emerged in female Tg2576 mice: time of day-dependent modulation of sleep was blunted relative to controls and rapid eye movement sleep as a percentage of time was lower in Tg2576 than in wild type controls. The rapid eye movement sleep deficit in 22 month-old female Tg2576 mice was abolished by brief passive immunization with an N-terminal antibody to Abeta. The Tg2576 model provides a uniquely powerful tool for studies on the pathophysiology of and treatments for sleep deficits and associated cholinergic abnormalities in AD.

  View details for DOI 10.1016/j.neuroscience.2004.11.018

  View details for Web of Science ID 000227258400011

  View details for PubMedID 15708480

• The measurement of sleep by actigraphy: Direct comparison of 2 commercially available actigraphs in a nonclinical population SLEEP Benson, K., Friedman, L., Noda, A., Wicks, D., Wakabayashi, E., Yesavage, J. 2004; 27 (5): 986-989

  Abstract

  To compare 2 commercially available actigraphs.Subjects wore the Actiwatch L and the Basic Mini-Motionlogger for 2 nights.Naturalistic.20 healthcare workers aged 24 to 64 years.Measures included sleep latency, total sleep time, wake after sleep onset, and sleep efficiency. Actiwatch L data were analyzed at 3 sensitivity settings.The Mini-Motionlogger reported more total sleep time, less wake after sleep onset, and greater sleep efficiency than the Actiwatch L set at high sensitivity. It also reported more wake after sleep onset than the Actiwatch L set at low sensitivity.Both devices achieved similar overall performance when the Actiwatch L was set at medium sensitivity.

  View details for Web of Science ID 000223451400023

  View details for PubMedID 15453559

• Stress and neuroendocrine reactivity among caucasian and hispanic women: A preliminary comparison of family dementia caregivers and non-caregivers Gallagher-Thompson, D., Rider, K. L., Shurgot, G. R., O'Hara, R., Kraemer, H. C., Yesavage, J. A. ELSEVIER SCIENCE INC. 2004: S344

  View details for DOI 10.1016/S0197-4580(04)81131-X

  View details for Web of Science ID 000223058701129

• Sleep in the Tg2576 mouse model for Alzheimer's disease: Effects of pharmacological and immunological therapeutics Wisor, J. P., Yesavage, J., Ryan, H. S., Murphy, G. M. ELSEVIER SCIENCE INC. 2004: S237

  View details for DOI 10.1016/S0197-4580(04)80796-6

  View details for Web of Science ID 000223058700794

• Validation of a 26-point telephone version of the mini-mental state examination JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Newkirk, L. A., Kim, J. A., Thompson, J. M., Tinklenberg, J. R., Yesavage, J. A., Taylor, J. L. 2004; 17 (2): 81-87

  Abstract

  The objective of this study was to assess the convergent validity of a 26-point Telephone Mini-Mental State Examination (MMSE) in a longitudinal cohort of 46 Alzheimer's disease (AD) patients. Paired in-person and telephone MMSE observations were collected within 35 days of each other. The setting was the Stanford/VA Alzheimer's Center in Palo Alto, California, and patients' residences. The 30-point Folstein MMSE was administered in-person, and a 26-point telephone version of the MMSE, adapted from the Adult Lifestyles and Function Interview (ALFI)-MMSE. Total scores for the in-person and telephone MMSE versions correlated strongly (Pearson's r =.88, P <.001). Hearing impairment and education level did not significantly affect telephone-based performance. The Telephone MMSE can be used to validly estimate in-person MMSE scores of patients with AD. Use of this practical measure can enhance reassessment if returning to the clinic is difficult or if a change in the patient's medical condition merits a check of mental status by telephone.

  View details for DOI 10.1177/0891988704264534

  View details for Web of Science ID 000223475100005

  View details for PubMedID 15157348

• VA practice patterns and practice guidelines for treating posttraumatic stress disorder JOURNAL OF TRAUMATIC STRESS Rosen, C. S., Chow, H. C., Finney, J. F., Greenbaum, M. A., Moos, R. H., Sheikh, J. I., Yesavage, J. A. 2004; 17 (3): 213-222

  Abstract

  Little is known about how recent ISTSS practice guidelines (E. B. Foa, T. M. Keane, & M. J. Friedman, 2000) compare with prevailing PTSD treatment practices for veterans. Prior to guideline dissemination, clinicians in 6 VA medical centers were surveyed in 1999 (n = 321) and in 2001 (n = 271) regarding their use of various assessment and treatment procedures. Practices most consistent with guideline recommendations included psychoeducation, coping skills training, attention to trust issues, depression and substance use screening, and prescribing of SSRIs, anticonvulsants, and trazodone. PTSD and trauma assessment, anger management, and sleep hygiene practices were provided less consistently. Exposure therapy was rarely used. Additional research is needed on training, clinical resources, and organizational factors that may influence VA implementation of guideline recommendations.

  View details for Web of Science ID 000221686900004

  View details for PubMedID 15253093

• Sleep/wake disruption in Alzheimer's disease: APOE status and longitudinal course JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Yesavage, J. A., Friedman, L., Kraemer, H., Tinklenberg, J. R., Salehi, A., Noda, A., Taylor, J. L., O'Hara, R., Murphy, G. 2004; 17 (1): 20-24

  Abstract

  Disturbed sleep is a major clinical problem in Alzheimer's disease (AD). Apolipoprotein epsilon4 (APOE epsilon4) carrier status may increase risk of AD, yet there are no data on relations between APOE status and progression of sleep disturbance in AD. The objective of this study was to determine if sleep parameters in AD patients change over time as a function of APOE carrier status. Forty-four community-dwelling AD patients with diagnosis of probable AD were followed from early stages of disease. Their sleep/wake parameters were compared according to APOE status. For APOE epsilon4 carriers, only wake after sleep onset (WASO) increased in association with lower cognitive function as indicated by the Mini-Mental State Examination (MMSE); for non-epsilon4 subjects, increases in WASO and declines in total sleep time, sleep efficiency, and the amplitude of the rest/activity circadian rhythm over time were associated with lower performance on the MMSE. In these data, APOE status was associated with the progression of sleep/wake disturbances in AD. Overall, there was greater deterioration on sleep parameters in patients negative for the epsilon4 allele.

  View details for DOI 10.1117/0891988703261994

  View details for Web of Science ID 000223474900004

  View details for PubMedID 15018693

• Use of a VA pharmacy database to screen for areas at high risk for disease: Parkinson's disease and exposure to pesticides JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Yesavage, J. A., Sheikh, J., Noda, A., Murphy, G., O'Hara, R., Hierholzer, R., Battista, M., Ashford, J. W., Kraemer, H. C., Tinklenberg, J. 2004; 17 (1): 36-38

  Abstract

  The purpose of this study was to assess whether pharmacy database information from US Department of Veterans Affairs (VA) medical centers could be used to screen for areas of higher Parkinson's disease prevalence in patients exposed to pesticides. The authors used pharmacy data sets and compared the use of antiparkinsonian medications at 2 VA medical centers in California: one in Palo Alto, near the ocean, and one in Fresno, downwind from extensively farmed parts of the Central Valley. They found that patients at Fresno had higher odds ratios (1.5-1.8) for the use of Parkinson's disease medications than patients at Palo Alto. These data are consistent with the observations of prior epidemiologic studies and suggest that VA pharmacy databases can prioritize locations for further epidemiologic research. However, a thorough exploration of alternative explanations is needed to reach definitive conclusions regarding the findings suggested by this method.

  View details for DOI 10.1117/0891988703258672

  View details for Web of Science ID 000223474900007

  View details for PubMedID 15018696

• Differential associations between entorhinal and hippocampal volumes and memory performance in older adults BEHAVIORAL NEUROSCIENCE Rosen, A. C., Prull, M. W., Gabrieli, J. D., Stoub, T., O'Hara, R., Friedman, L., Yesavage, J. A., DeToledo-Morrell, L. 2003; 117 (6): 1150-1160

  Abstract

  Magnetic resonance imaging-derived entorhinal and hippocampal volumes were measured in 14 nondemented, community-dwelling older adults. Participants were selected so that memory scores from 2 years prior to scanning varied widely but were not deficient relative to age-appropriate norms. A median split of these memory scores defined high-memory and low-memory groups. Verbal memory scores at the time of imaging were lower, and entorhinal and hippocampal volumes were smaller, in the low-memory group than in the high-memory group. Left entorhinal cortex volume showed the strongest correlation (r= .79) with immediate recall of word lists. Left hippocampal volume showed the strongest correlation (r= .57) with delayed paragraph recall. These results suggest that entorhinal and hippocampal volumes are related to individual differences in dissociable kinds of memory performance among healthy older adults.

  View details for DOI 10.1037/0735-7044.117.6.1150

  View details for Web of Science ID 000187402300004

  View details for PubMedID 14674836

• Age and disease severity predict choice of atypical neuroleptic: a signal detection approach to physicians' prescribing decisions JOURNAL OF PSYCHIATRIC RESEARCH Yesavage, J. A., Hoblyn, J., Sheikh, J., Tinklenberg, J. R., Noda, A., O'Hara, R., Fenn, C., Mumenthaler, M. S., Friedman, L., Kraemer, H. C. 2003; 37 (6): 535-538

  Abstract

  We used a novel application of a signal detection technique, receiver operator characteristics (ROC), to describe factors entering a physician's decision to switch a patient from a typical high potency neuroleptic to a particular atypical, olanzapine (OLA) or risperidone (RIS).ROC analyses were performed on pharmacy records of 476 VA patients who had been treated on a high potency neuroleptic then changed to either OLA or RIS.Overall 68% patients switched to OLA and 32% to RIS. The best predictor of neuroleptic choice was age at switch, with 78% of patients aged less than 55 years receiving OLA and 51% of those aged greater than or equal to 55 years receiving OLA (chi(2)=38.2, P<0.001). Further analysis of the former group indicated that adding the predictor of one or more inpatient days to age increased the likelihood of an OLA switch from 78% to 85% (chi(2)=7.3, P<0.01) while further analysis of the latter group indicated that adding the predictor of less than 10 inpatients days to age decreased the likelihood of an OLA switch from 51% to 45% (chi(2)=7.0, P<0.01).ROC analyses have the advantage over other analyses, such as regression techniques, insofar as their "cut-points" are readily interpretable, their sequential use forms an intuitive "decision tree" and allows the potential identification of clinically relevant "subgroups". The software used in this analysis is in the public domain (http://mirecc.stanford.edu).

  View details for DOI 10.1016/S0022-3956(03)00053-0

  View details for Web of Science ID 000186239700010

  View details for PubMedID 14563385

• Donepezil and flight simulator performance: Effects on retention of complex skills - Reply NEUROLOGY Mumenthaler, M. S., Yesavage, J. A., Taylor, J. L., Friedman, L., O'Hara, R., Sheikh, J., Tinklenberg, J., Whitehouse, P. J. 2003; 61 (5): 721-721

  View details for Web of Science ID 000185187000038

• Development of diagnostic criteria for defining sleep disturbance in Alzheimer's disease JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Yesavage, J. A., Friedman, L., Ancoli-Israel, S., Bliwise, D., Singer, C., Vitiello, M. V., Monjan, A. A., Lebowitz, B. 2003; 16 (3): 131-139

  Abstract

  This article proposes new standards for identifying, defining, and naming sleep/wake cycle disturbances associated with Alzheimer's disease (AD) to aid in more effective research, including the development and testing of potential treatments. Many AD patients develop sleep/wake cycle disturbances associated with distress, depression, and sleep disturbances in the caregiver, as well as early nursing home placement for the patient. The Food and Drug Administration Psychopharmacological Drugs Advisory Committee has emphasized the need for a comprehensive diagnostic system. A key point made by the committee was that behavioral problems associated with dementia (including sleep and chronobiological disturbances) are scientifically and clinically valid targets of pharmacologic treatment. However, current diagnostic criteria preclude development of FDA-acceptable studies of pharmacological interventions because they do not include the required specific indications for treatment. This article attempts to develop better-defined provisional criteria with the goal of promoting epidemiological, physiological, and, especially, pharmacological research on sleep/wake disturbances.

  View details for DOI 10.1177/0891988703255684

  View details for Web of Science ID 000223380400001

  View details for PubMedID 12967054

• Psychoactive drugs and pilot performance: A comparison of nicotine, donepezil, and alcohol effects NEUROPSYCHOPHARMACOLOGY Mumenthaler, M. S., Yesavage, J. A., Taylor, J. L., O'Hara, R., Friedman, L., LEE, H., Kraemer, H. C. 2003; 28 (7): 1366-1373

  Abstract

  The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing I: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the ES of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine)=0.80; ES (donepezil)=1.02; ES (alcohol acute)=-3.66; ES (alcohol 8 h)=-0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention. Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol.

  View details for DOI 10.1038/sj.npp.1300202

  View details for Web of Science ID 000183773000018

  View details for PubMedID 12784106

• Use of an external mnemonic to augment the efficacy of an internal mnemonic in older adults INTERNATIONAL PSYCHOGERIATRICS Brooks, J. O., Friedman, L., Yesavage, J. A. 2003; 15 (1): 59-67

  Abstract

  To evaluate the impact of external memory devices on the efficacy of a package of internal mnemonic techniques. Participants wrote two types of lists during the study phase: (a) a list of study words and/or (b) a loci list. At recall, participants were not allowed to refer to either of the lists they had written during the study.2 x 2 factorial with writing study words ("write" or "not write") and writing down a previously established loci list ("write" or "not write") manipulated as between-participants variables.68 community-dwelling adults 55 years of age and older who wished to improve their memory.Free word recall.There were statistically significant effects of writing the loci list, but not of writing the list of study words. Scores were higher when participants wrote the loci lists compared to when they did not.Use of external mnemonics may enhance the efficacy of internal mnemonics, even when the external mnemonic is not used at the time of recall.

  View details for Web of Science ID 000183289600007

  View details for PubMedID 12834200

• Sleep/wake cycle disturbance in Alzheimer's disease: Longitudinal change in relation to APOE status Yesavage, J., Friedman, L., Kraemer, H., Murphy, G., Salehi, A., O'Hara, R., Noda, A., Taylor, J., Tinklenberg, J. CAMBRIDGE UNIV PRESS. 2003: 241–241

  View details for Web of Science ID 000222209400569

• Variable effects of aging on frontal lobe contributions to memory NEUROREPORT Rosen, A. C., Prull, M. W., O'Hara, R., Race, E. A., Desmond, J. E., Glover, G. H., Yesavage, J. A., Gabrieli, J. D. 2002; 13 (18): 2425-2428

  Abstract

  Declarative memory declines with age, but there is profound variation in the severity of this decline. Healthy elderly adults with high or low memory scores and young adults viewed words under semantic or non-semantic encoding conditions while undergoing fMRI. Young adults had superior memory for the words, and elderly adults with high memory scores had better memory for the words than those with low memory scores. The elderly with high scores had left lateral and medial prefrontal activations for semantic encoding equal to the young, and greater right prefrontal activation than the young. The elderly with low scores had reduced activations in all three regions relative to the elderly with high memory scores. Thus, successful aging was characterized by preserved left prefrontal and enhanced right prefrontal activation that may have provided compensatory encoding resources.

  View details for DOI 10.1097/01.wnr.0000048001.96487.05

  View details for Web of Science ID 000180673200010

  View details for PubMedID 12499842

• Ethical, and practical issues in applying functional imaging to the clinical management of Alzheimer's disease BRAIN AND COGNITION Rosen, A. C., Bokde, A. L., Pearl, A., Yesavage, J. A. 2002; 50 (3): 498-519

  Abstract

  This review outlines ethical, legal, and practical issues related to conducting functional imaging research with Alzheimer's disease (AD) patients. Imaging techniques, with an emphasis on functional MRI and positron emission tomography, are compared and contrasted with respect to the manner in which they can be applied to issues of clinical relevance to AD. Methodological difficulties are raised to assist with critical evaluation of current imaging results. Various potential clinical applications of functional imaging are briefly reviewed and discussed with respect to associated ethical conflicts.

  View details for Web of Science ID 000180058100013

  View details for PubMedID 12480493

• On disentangling states versus traits: Demonstration of a new technique using the Alzheimer's disease assessment scale ALZHEIMER DISEASE & ASSOCIATED DISORDERS Taylor, J. L., Kraemer, H. C., Noda, A., Friedman, L., Zarcone, V., Tinklenberg, J. R., Yesavage, J. A. 2002; 16 (4): 254-260

  Abstract

  Part of the challenge in research on degenerative neurologic disease relates to distinguishing those measurements that essentially describe patient characteristics stable across the course of illness (traits) from those that vary systematically within subjects (states), particularly those specifically related to stage or duration of illness. A components-of-variance approach was used to examine the state versus trait aspects of the Alzheimer's Disease Assessment Scale (ADAS) Cognitive and Noncognitive subscales, a clinical instrument frequently used in research on Alzheimer disease. Subjects were 190 patients with probable AD followed longitudinally. Stage of illness was indexed by mental status scores. Analysis of variance was used to partition total variance into that associated with subjects (trait), stages (state: stage), subjects x stages (state: other), and error. ADAS Cognitive scores were strongly related to stage of illness (83% of true variance). ADAS Noncognitive scores were modestly related to stage (approximately 21% of true variance) and moderately related to state: other (47%). We discuss how state-trait analyses can be helpful in focusing attention on those areas of assessment most likely to accomplish specific objectives.

  View details for Web of Science ID 000179640800007

  View details for PubMedID 12468900

• Modeling the prevalence and incidence of Alzheimer's disease and mild cognitive impairment European Winter Conference on Brain Research Yesavage, J. A., O'Hara, R., Kraemer, H., Noda, A., Taylor, J. L., Ferris, S., Gely-Nargeot, M. C., Rosen, A., Friedman, L., Sheikh, J., Derouesne, C. PERGAMON-ELSEVIER SCIENCE LTD. 2002: 281–86

  Abstract

  A number of systems have been proposed for classifying older adults who suffer from cognitive impairment or decline but do not yet meet criteria for Alzheimer's disease (AD). The classification, Mild Cognitive Impairment (MCI), has attracted much attention. It uses relatively specific diagnostic criteria and individuals who meet these criteria appear to be at substantial risk for the development of AD. However, little data is available to define the prevalence of MCI in any age group. We propose a simple mathematical model for the progression of patients from Non-Affected (NA) to MCI to AD. This first-order Markov model defines the likely prevalence of MCI at specific ages. Primary assumptions of the model include an AD prevalence of 1% at age 60 increasing to 25% at age 85 and a conversion rate from MCI to AD of 10% constant across all ages considered. We used the best available information for our model and found (1) that the MCI prevalence increased from 1% at age 60 to 42% at age 85 and (2) that the conversion rate from NA to MCI increased from 1% per year at age 60 to 11% at age 85. In conclusion, this model allows estimation of prevalence of MCI and conversion from NA to MCI based upon known prevalences of AD, conversion rates of MCI to AD, and death rates. Due to its substantial prevalence, MCI may be an important target for screening and possible intervention.

  View details for Web of Science ID 000178254700002

  View details for PubMedID 12127595

• Interactive influences on BVRT performance level: geriatric considerations ARCHIVES OF CLINICAL NEUROPSYCHOLOGY Coman, E., Moses, J. A., Kraemer, H. C., Friedman, L., Benton, A. L., Yesavage, J. 2002; 17 (6): 595-610

  Abstract

  We examined the interactive influence of specific demographic and diagnostic variables on Benton Visual Retention Test (BVRT) performance in three commonly presenting groups of older adults. Cross-sectional data from three archival samples were utilized: "normals" (n=156), "normals with memory concerns" (n=435), and a "mixed neurologic" group (n=196). In both normal groups, as well as in a "no/low deficit" neurologic subgroup, we confirmed that the higher one's age, the lower their BVRT accuracy, while the higher one's level of education, the greater their BVRT accuracy (at least through age 84). For normal subjects, gender had no impact on BVRT performance. Variability in BVRT performance increased consistently, but not significantly, through age 85.

  View details for Web of Science ID 000178747900006

  View details for PubMedID 14591858

• Donepezil and flight simulator performance: Effects on retention of complex skills NEUROLOGY Yesavage, J. A., Mumenthaler, M. S., Taylor, J. L., Friedman, L., O'Hara, R., Sheikh, J., Tinklenberg, J., Whitehouse, P. J. 2002; 59 (1): 123-125

  Abstract

  We report a randomized, double-blind, parallel group, placebo-controlled study to test the effects of the acetylcholinesterase inhibitor, donepezil (5 mg/d for 30 days), on aircraft pilot performance in 18 licensed pilots with mean age of 52 years. After 30 days of treatment, the donepezil group showed greater ability to retain the capacity to perform a set of complex simulator tasks than the placebo group, p < 0.05. Donepezil appears to have beneficial effects on retention of training on complex aviation tasks in nondemented older adults.

  View details for Web of Science ID 000176622600025

  View details for PubMedID 12105320

• Sleep/wake cycle disturbance in Alzheimer's disease: How much is due to an inherent trait? INTERNATIONAL PSYCHOGERIATRICS Yesavage, J. A., Taylor, J. L., Kraemer, H., Noda, A., Friedman, L., Tinklenberg, J. R. 2002; 14 (1): 73-81

  Abstract

  Major advances in understanding the physiology and genetics of circadian rhythm in the past decade challenge the researcher of sleep/wake disorders in Alzheimer's disease (AD) to distinguish patient characteristics stable across the course of illness ("traits") from characteristics that vary with stage of illness ("states"). A components-of-variance approach with a repeated measures model was used to examine the between-subjects variance over time ("trait") vs. within-subjects ("state") variance in 42 patients with probable AD followed, on average, over 2 years on actigraphic sleep/wake measures. Mental status scores indexed stage of illness. Actigraphic measures of sleep efficiency and circadian rhythmicity appeared predominantly "trait," with between-individual differences accounting for over 55% of variance compared to the less than 5% of variance related to stage of cognitive impairment. We discuss how "state-trait" analyses can be helpful in identifying areas of assessment most likely to be fruitful objectives of physiologic and genetic research on sleep/wake disturbance in AD.

  View details for Web of Science ID 000176217400008

  View details for PubMedID 12094910

• How well are clinicians following dementia practice guidelines? ALZHEIMER DISEASE & ASSOCIATED DISORDERS Rosen, C. S., Chow, H. C., Greenbaum, M. A., Finney, J. F., Moos, R. H., Sheikh, J. I., Yesavage, J. A. 2002; 16 (1): 15-23

  Abstract

  Although there are numerous clinical guidelines regarding the management of dementia, there have been few studies on their implementation in practice. Clinicians in six United States Department of Veterans Affairs medical centers (n = 200, 85% response rate) were surveyed regarding their use of practices recommended in the California Workgroup Guidelines for Alzheimer's Disease Management. The majority of providers (89% to 73%) reported that they routinely conducted neurological examinations, obtained histories from caregivers, discussed the diagnosis with the patient's family, discussed durable power of attorney, and made legally-required reports of drivers with dementia. Roughly two-thirds of providers said they routinely conducted cognitive screening examinations, screened for depression, reported elder abuse, and discussed care needs and decision-making issues with patients' families. Only half of all outpatient providers implemented caregiver support practices for at least half of their patients. Clinicians' choices of medications for cognition, mood, and behavior problems were broadly consistent with current practice guidelines. These results suggest possible priorities for quality improvement efforts. Further research is needed to clarify reasons for particular gaps between guidelines and practice and to identify specific targets for intervention.

  View details for Web of Science ID 000174273000003

  View details for PubMedID 11882745

• Which Alzheimer patients are at risk for rapid cognitive decline? JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY O'Hara, R., Thompson, J. M., Kraemer, H. C., Fenn, C., Taylor, J. L., Ross, L., Yesavage, J. A., Bailey, A. M., Tinklenberg, J. R. 2002; 15 (4): 233-238

  Abstract

  In the current study of 1062 Alzheimer's disease (AD) patients, we employed receiver operating characteristic curve analysis to identify characteristics of patients at increased risk for rapid cognitive decline. The patients are participants at one of the nine Alzheimer's Disease Research Centers of California. Rapid decline was defined as a 3-point or greater loss on the Mini-Mental State Examination (MMSE) per year, post visit. The independent variables were age at clinic visit, age at symptom onset of AD, MMSE at patient visit, years of education, gender, ethnicity, living arrangement, presence of aphasia, delusions, hallucinations, and extrapyramidal signs. Receiver operating characteristic curve analysis indicated that AD patients presenting with moderate to severe aphasia, age at clinic visit of 75 years or less, and an MMSE greater than 7 were at increased risk for rapid cognitive decline. This information could help clinicians target these patients for pharmacologic interventions, facilitate long-term care planning, and potentially create savings by delaying or stabilizing the course of the disease.

  View details for Web of Science ID 000179584400009

  View details for PubMedID 12489920

• CSF hypocretin/orexin levels in narcolepsy and other neurological conditions NEUROLOGY Ripley, B., Overeem, S., Fujiki, N., Nevsimalova, S., Uchino, M., Yesavage, J., Di Monte, D., DOHI, K., Melberg, A., Lammers, G. J., Nishida, Y., Roelandse, F. W., Hungs, M., Mignot, E., Nishino, S. 2001; 57 (12): 2253-2258

  Abstract

  To examine the specificity of low CSF hypocretin-1 levels in narcolepsy and explore the potential role of hypocretins in other neurologic disorders.A method to measure hypocretin-1 in 100 microL of crude CSF sample was established and validated. CSF hypocretin-1 was measured in 42 narcolepsy patients (ages 16-70 years), 48 healthy controls (ages 22-77 years,) and 235 patients with various other neurologic conditions (ages 0-85 years).As previously reported, CSF hypocretin-1 levels were undetectably low (<100 pg/mL) in 37 of 42 narcolepsy subjects. Hypocretin-1 levels were detectable in all controls (224-653 pg/mL) and all neurologic patients (117-720 pg/mL), with the exception of three patients with Guillain-Barré syndrome (GBS). Hypocretin-1 was within the control range in most neurologic patients tested, including patients with AD, PD, and MS. Low but detectable levels (100-194 pg/mL) were found in a subset of patients with acute lymphocytic leukemia, intracranial tumors, craniocerebral trauma, CNS infections, and GBS.Undetectable CSF hypocretin-1 levels are highly specific to narcolepsy and rare cases of GBS. Measuring hypocretin-1 levels in the CSF of patients suspected of narcolepsy is a useful diagnostic procedure. Low hypocretin levels are also observed in a large range of neurologic conditions, most strikingly in subjects with head trauma. These alterations may reflect focal lesions in the hypothalamus, destruction of the blood brain barrier, or transient or chronic hypofunction of the hypothalamus. Future research in this area is needed to establish functional significance.

  View details for Web of Science ID 000172891500018

  View details for PubMedID 11756606

• Context processing in older adults: Evidence for a theory relating cognitive control to neurobiology in healthy aging 40th Annual Meeting of the Psychonomic-Society Braver, T. S., Barch, D. M., Keys, B. A., Carter, C. S., Cohen, J. D., Kaye, J. A., Janowsky, J. S., Taylor, S. F., Yesavage, J. A., Mumenthaler, M. S., Jagust, W. J., Reed, B. R. AMER PSYCHOLOGICAL ASSOC. 2001: 746–63

  Abstract

  A theory of cognitive aging is presented in which healthy older adults are hypothesized to suffer from disturbances in the processing of context that impair cognitive control function across multiple domains, including attention, inhibition, and working memory. These cognitive disturbances are postulated to be directly related to age-related decline in the function of the dopamine (DA) system in the prefrontal cortex (PFC). A connectionist computational model is described that implements specific mechanisms for the role of DA and PFC in context processing. The behavioral predictions of the model were tested in a large sample of older (N = 81) and young (N = 175) adults performing variants of a simple cognitive control task that placed differential demands on context processing. Older adults exhibited both performance decrements and, counterintuitively, performance improvements that are in close agreement with model predictions.

  View details for DOI 10.1037//0096-3445.130.4.746

  View details for Web of Science ID 000172286300009

  View details for PubMedID 11757878

• Therapeutic approaches to age-associated neurocognitive disorders. Dialogues in clinical neuroscience O'Hara, R., Derouesné, C., Fountoulakis, K. N., Yesavage, J. A. 2001; 3 (3): 191-213

  Abstract

  The United Nations projects that the number of individuals with dementia in developed countries alone will be approximately 36,7 million by the year 2050. International recognition of the significant emotional and economic burden of Alzheimer's disease has been matched by a dramatic increase in the development of pharmacological and nonpharmacological approaches to this illness in the past decade. Changing demographics have underscored the necessity to develop similar approaches for the remediation of the cognitive impairment associated with more benign syndromes, such as mild cognitive impairment (MCI) and age-associated cognitive decline (AACD). The present article aims to provide an overview of the most current therapeutic approaches to age-associated neurocognitive disorders. Additionally, it discusses the conceptual and methodological issues that surround the design, implementation, and interpretation of such approaches.

  View details for PubMedID 22033831

  View details for PubMedCentralID PMC3181653

• Influence of the menstrual cycle on flight simulator performance after alcohol ingestion JOURNAL OF STUDIES ON ALCOHOL Mumenthaler, M. S., O'Hara, R., Taylor, J. L., Friedman, L., Yesavage, J. A. 2001; 62 (4): 422-433

  Abstract

  Previous studies investigating the influence of the menstrual cycle on cognitive functioning of women after alcohol ingestion have obtained inconsistent results. The present study tested the hypothesis that flight simulator performance during acute alcohol intoxication and 8 hours after drinking differs between the menstrual and the luteal phase of the menstrual cycle.White female pilots (N = 24) were tested during the menstrual and the luteal phases of their menstrual cycles. On each test day they performed a baseline simulator flight, consumed 0.67 g/kg ethanol, and performed an acute-intoxication and an 8-hour-carryover simulator flight.Subjects reached highly significant increases in estradiol (E2) as well as progesterone (P) levels during the luteal test day. Yet, there were no significant differences in overall flight performance after alcohol ingestion between the menstrual and luteal phases during acute intoxication or at 8-hour carryover. We found no correlations between E, or P levels and overall flight performance. However, there was a statistically significant Phase x Order interaction: Pilots who started the experiment with their menstrual day were less susceptible to the effects of alcohol during the second test day than were pilots who started with their luteal day.The tested menstrual cycle phases and varying E2 and P levels did not significantly influence postdrink flight performance. Because the present study included a comparatively large sample size and because it involved complex "real world" tasks (piloting an aircraft), we believe that the present findings are important. We hope that our failure to detect menstrual cycle effects will encourage researchers to include women in their investigations of alcohol effects and human performance.

  View details for Web of Science ID 000170348900002

  View details for PubMedID 11523532

• Rate of cognitive decline in AD is accelerated by the interleukin-1 alpha-889*1 allele NEUROLOGY Murphy, G. M., Claassen, J. D., DeVoss, J. J., Pascoe, N., Taylor, J., Tinklenberg, J. R., Yesavage, J. A. 2001; 56 (11): 1595-1597

  Abstract

  The reason for differences in rate of cognitive decline in AD is unknown. The interleukin-1 alpha (IL-1 alpha) -889 *2 allele is associated with increased risk for AD. Surprisingly, in a sample of 114 patients followed for an average of 3.8 years, individuals homozygous for the IL-1 alpha -889 *1 allele declined significantly more rapidly on the Mini-Mental State Examination than did others. There was no difference in rate of decline between patients with and without the APOE epsilon 4 allele. These results support the hypothesis that inflammation is important in the clinical course of AD.

  View details for Web of Science ID 000169187100033

  View details for PubMedID 11402127

• Relationship between variations in estradiol and progesterone levels across the menstrual cycle and human performance PSYCHOPHARMACOLOGY Mumenthaler, M. S., O'Hara, R., Taylor, J. L., Friedman, L., Yesavage, J. A. 2001; 155 (2): 198-203

  Abstract

  Studies about whether or not the cognitive performance of women is influenced by changes in levels of sex steroid hormones across the menstrual cycle have produced ambiguous results.This study tested whether flight simulator performance differs significantly between the menstrual and the luteal phase of the menstrual cycle.In a within-subjects design, 24 female pilots were tested twice during their menstrual cycle: once during the menstrual and once during the luteal phase. On both test days they performed a 75-min simulator flight in a Frasca 141, a popular pilot training device.Despite highly significant differences in estradiol (E2) as well as progesterone (P) levels on the 2 test days, and despite excluding subjects with anovulatory cycles from the analyses, there were no significant differences in overall flight performance between the menstrual and luteal phases. We found no significant correlations between E2 or P levels and flight performance.We found no evidence that the tested menstrual cycle phases and their associated E2 and P levels significantly influence flight simulator performance. We consider these negative findings based on 24 subjects meaningful because previous studies on the influence of menstrual cycle on cognitive performance have not involved complex "real world" tasks such as piloting an aircraft and they obtained inconsistent results.

  View details for Web of Science ID 000168778000013

  View details for PubMedID 11401010

• One year of insulin-like growth factor I treatment does not affect bone density, body composition, or psychological measures in postmenopausal women JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Friedlander, A. L., Butterfield, E., Moynihan, S., Grillo, J., Pollack, M., Holloway, L., Friedman, L., Yesavage, J., Matthias, D. F., Lee, S., Marcus, R., Hoffman, A. R. 2001; 86 (4): 1496-1503

  Abstract

  The activity of the hypothalamic-GH-insulin-like growth factor I (hypothalamic-GH-IGF-I) axis declines with age, and some of the catabolic changes of aging have been attributed to the somatopause. The purpose of this investigation was to determine the impact of 1 yr of IGF-I hormone replacement therapy on body composition, bone density, and psychological parameters in healthy, nonobese, postmenopausal women over 60 yr of age. Subjects (n = 16, 70.6 +/- 2.0 yr, 71.8 +/- 2.8 kg) were randomly assigned to either the self-injection IGF-I (15 microg/kg twice daily) or placebo group and were studied at baseline, at 6 months, and at 1 yr of treatment. There were no significant differences between the IGF-I and placebo groups in any of the measured variables at baseline. Fasting blood IGF-I levels were significantly elevated above baseline values (65.6 +/- 11.9 ng/mL) at 6 months (330.0 +/- 52.8) and 12 months (297.7 +/- 40.8) in the IGF-I treated group but did not change in the placebo subjects. Circulating levels of IGF-binding protein-1 and -3 were unaffected by the IGF-I treatment. Bone mineral density of the forearm, lumbar spine, hip, and whole body [as measured by dual-energy x-ray absorptiometry (DXA)] did not change in either group. Similarly, there was no difference in DXA-measured lean mass, fat mass, or percent body fat throughout the treatment intervention. Muscle strength values (grip, bench press, leg press), blood lipid parameters (cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), and measures of postmeal glucose disposal were not altered by IGF-I treatment, although postmeal insulin levels were lower in the IGF-I subjects at 12 months. IGF-I did not affect bone turnover markers (osteocalcin and type I collagen N-teleopeptide), but subjects who were taking estrogen had significantly lower turnover markers than subjects who were not on estrogen at baseline, 6 months, and 12 months. Finally, the psychological measures of mood and memory were also not altered by the intervention. Despite the initial intent to recruit additional subjects, the study was discontinued after 16 subjects completed the protocol, because the preliminary analyses above indicated that no changes were occurring in any outcome variables, regardless of treatment regimen. Therefore, we conclude that 1 yr of IGF-I treatment, at a dose sufficient to elevate circulating IGF-I to young normal values, is not an effective means to alter body composition or blood parameters nor improve bone density, strength, mood, or memory in older women.

  View details for Web of Science ID 000168243000010

  View details for PubMedID 11297574

• Event-related brain potential evidence of spared knowledge in Alzheimer's disease PSYCHOLOGY AND AGING Ford, J. M., Askari, N., Gabrieli, J. D., Mathalon, D. H., Tinklenberg, J. R., Menon, V., Yesavage, J. 2001; 16 (1): 161-176

  Abstract

  The authors recorded event-related brain potentials (ERPs) to picture primes and word targets (picture-name verification task) in patients with Alzheimer's disease (AD) and in elderly and young participants. N400 was more negative to words that did not match pictures than to words that did match pictures in all groups: In the young, this effect was significant at all scalp sites; in the elderly, it was only at central-parietal sites; and in AD patients, it was limited to right central-parietal sites. Among AD patients pretested with a confrontation-naming task to identify pictures they could not name, neither the N400 priming effect nor its scalp distribution was affected by ability to name pictures correctly. This ERP evidence of spared knowledge of these items was complemented by 80% performance accuracy. Thus, although the name of an item may be inaccessible in confrontation naming, N400 shows that knowledge is intact enough to prime cortical responses.

  View details for DOI 10.1037//0882-7974.16.1.161

  View details for Web of Science ID 000171004800014

  View details for PubMedID 11302364

• Remote memory for public figures in Alzheimer's disease: Relationships to regional cortical and limbic brain volumes JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY Fama, R., Shear, P. K., Marsh, L., Yesavage, J. A., Tinklenberg, J. R., Lim, K. O., Pfefferbaum, A., Sullivan, E. V. 2001; 7 (3): 384-390

  Abstract

  This study examined the relationships between regional cortical and hippocampal brain volumes and components of remote memory (recall, recognition, sequencing, and photo naming of presidential candidates) in 13 individuals with Alzheimer's disease (AD). Recognition and sequencing of remote memory for public figures were associated with regional cortical volumes. Specifically, lower recognition and sequencing scores were associated with smaller parietal-occipital cortical volumes; poorer sequencing was also associated with smaller prefrontal cortical volumes. By contrast, poorer anterograde but not remote memory scores were correlated with smaller hippocampal volumes. Within the constraints of the brain regions measured, these findings highlight the importance of the posterior cortical areas for selective remote memory processes and provide support for the dissociation between cortically mediated remote memory and hippocampally mediated anterograde memory.

  View details for Web of Science ID 000168425100012

  View details for PubMedID 11311039

• Hearing impairment and serial word recall in older adults EXPERIMENTAL AGING RESEARCH Pearman, A., Friedman, L., Brooks, J. O., Yesavage, J. A. 2000; 26 (4): 383-391

  Abstract

  The objective of this work was to study the differences in performance on a nonauditory memory task between older volunteers with and without hearing impairment. The design was cross-sectional. Three-hundred-forty-four community-dwelling adults aged 55 to 93 years, who volunteered for a mnemonic training class served as participants. Participants' hearing was tested with a Maico MA-27 portable audiometer. The dependent measure was performance on a visually presented serial word recall test. Participants were also asked to report whether they had a problem with their hearing. Hearing impairment was associated with poor performance on a serial word recall task, even after controlling for age-related differences on that task. Hearing acuity appears to be related to serial word recall in older adults. Because auditory presentations were not involved, this relation raises the question of whether hearing loss may be concomitant with other changes that affect cognitive abilities.

  View details for Web of Science ID 000165086400008

  View details for PubMedID 11091943

• Ethanol pharmacokinetics in white women: Nonlinear model fitting versus zero-order elimination analyses ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Mumenthaler, M. S., Taylor, J. L., Yesavage, J. A. 2000; 24 (9): 1353-1362

  Abstract

  Studies have shown repeatedly that ethanol pharmacokinetics are not linear, yet most researchers still determine ethanol elimination by linear, zero-order kinetics. The goals of the present work were to: (1) fit four nonlinear pharmacokinetic models to mean breath alcohol concentration (BrAC)-time data of 27 women and determine the best-fit model; (2) fit the determined best-fit model to individual BrAC data and estimate the pharmacokinetic parameters; and (3) compare the method of nonlinear model fitting with the classical zero-order elimination method and determine in which cases the classical approach is justified.Twenty-seven healthy white women ingested four drinks (total of 0.67 g x kg(-1)) of ethanol on two test days. Approximately 24 breath ethanol samples (for pharmacokinetic analyses) and one blood sample (for hormonal markers) were taken per day. Pharmacokinetic model evaluation was based on the coefficient of variation, the weighted residual sum of squares, and the sequence of the weighted residuals. Because hormonal changes across the menstrual cycle did not significantly influence ethanol pharmacokinetics, data from the two test days were pooled.The best-fit model was a one-compartment open model with first-order absorption and sequential first-order elimination, followed by Michaelis-Menten elimination kinetics. Fitting this model to the individual BrAC data yielded mean ka = 0.062 hr(-1), Vd = 0.457 L x kg(-1), ke = 0.011 hr(-1), Vmax = 0.136 g x L(-1) x hr(-1), and Km = 0.096 g x L(-1). For the classical analyses, mean time to peak BrAC = 1.83 hr, disappearance rate = 0.179 g x L(-1) x hr(-1), and area under the blood ethanol-time curve (AUC) = 2.884 g x L(-1) x hr. Correlational analyses showed that more frequent drinkers eliminated ethanol significantly faster and reached significantly lower AUC than less frequent drinkers.After multiple dose ingestion in white women, classical zero-order elimination analyses can be applied only to a limited portion of the descending BrAC-time curve. They seem justified and practical from 0.5 hr after peak BrAC until BrAC reaches 0.2 g x L(-1). To describe ethanol pharmacokinetics across the entire BrAC-time curve, however, sophisticated nonlinear model fitting is required.

  View details for Web of Science ID 000089364800005

  View details for PubMedID 11003200

• A retrospective chart review of gabapentin for the treatment of aggressive and agitated behavior in patients with dementias AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Hawkins, J. W., Tinklenberg, J. R., Sheikh, J. I., PEYSER, C. E., Yesavage, J. A. 2000; 8 (3): 221-225

  Abstract

  In a 24-patient case series from retrospective chart review, the authors examined the use of gabapentin for the treatment of aggressive and agitated behaviors in nursing home patients with a DSM-IV diagnosis of dementia. On Clinical Global Rating Scale scores, 17 of 22 patients were much or greatly improved; 4 were minimally improved; and only 1 remained unchanged. Two of the 24 patients discontinued use of the medication because of excessive sedation. No other significant side effects were noted in treatment lasting up to 2 years.

  View details for Web of Science ID 000088230700007

  View details for PubMedID 10910420

• A longitudinal study of Apolipoprotein-E genotype and depressive symptoms in community-dwelling older adults AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Mauricio, M., O'Hara, R., Yesavage, J. A., FRIEDMAN, E., Kraemer, H. C., Van de Water, M., Murphy, G. M. 2000; 8 (3): 196-200

  Abstract

  The Apolipoprotein-E (APOE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD) and cognitive decline in older adults. Depression may also be a risk factor for dementia, and depression is important in the differential diagnosis of dementia. The authors performed a 5-year longitudinal study of APOE genotype and change in Geriatric Depression Scale scores in 113 community-dwelling older adults. No association was observed between APOE genotype and change in depressive symptoms. These results do not support the hypothesis that the APOE epsilon 4 allele is associated with depression. Important objections have been raised to APOE genotyping in the diagnosis of AD. However, the specificity of APOE genotyping in AD diagnosis would not appear to be compromised by an association with depression.

  View details for Web of Science ID 000088230700003

  View details for PubMedID 10910416

• Combined assessment of tau and neuronal thread protein in Alzheimer's disease CSF NEUROLOGY Kahle, P. J., Jakowec, M., Teipel, S. J., Hampel, H., Petzinger, G. M., Di Monte, D. A., Silverberg, G. D., Moller, H. J., Yesavage, J. A., Tinklenberg, J. R., Shooter, E. M., Murphy, G. M. 2000; 54 (7): 1498-1504

  Abstract

  Comparative study of CSF levels of tau and AD7C-neuronal thread protein (NTP) in patients with AD and control subjects.AD is characterized by neurofibrillary tangles composed of the abnormally hyperphosphorylated microtubule-associated protein tau. AD7C-NTP is a proposed AD marker expressed at early stages of neurofibrillary degeneration.Enzyme-linked immunosorbent assays specific for tau and AD7C-NTP. CSF samples were obtained from 35 demented patients (25 with antemortem clinical diagnosis of probable AD, 5 with neuropathologic diagnosis of definite AD, 5 with Lewy body pathology), 29 nondemented patients with PD, and 16 elderly healthy control subjects. Receiver operating characteristics (ROC) and multivariate discriminant analysis for AD versus controls. Correlational analysis of CSF tau and AD7C-NTP and of each marker with Mini-Mental State Examination (MMSE) scores was performed.Levels of both tau and AD7C-NTP were significantly elevated in the AD patients compared with control subjects. ROC analysis showed that CSF tau distinguished between patients with AD and nondemented control subjects with 63% sensitivity and 89% specificity, AD7C-NTP with 70% sensitivity and 87% specificity. Combined evaluation of both markers with discriminant analysis raised the specificity to 93% at a 63% sensitivity level. Both markers positively correlated with each other within the AD group, but not among control subjects. CSF levels of AD7C-NTP, but not of tau, showed a small but significant inverse correlation (r = -0.43) with MMSE scores of AD patients.CSF levels of tau and AD7C-NTP may be useful biomarkers for AD.

  View details for Web of Science ID 000086460900021

  View details for PubMedID 10751266

• Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease Annual Meeting of the International-Neuropsychological-Society Fama, R., Sullivan, E. V., Shear, P. K., Stein, M., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. AMER PSYCHOLOGICAL ASSOC. 2000: 265–76

  Abstract

  Content and contextual memory for remote public figures and events was assessed with a modified version of the Presidents Test in patients with Alzheimer's disease (AD) or Parkinson's disease (PD). Contributions of executive functioning, semantic memory, and explicit anterograde memory to remote memory abilities were also examined. The AD group had temporally extensive deficits in content and contextual remote memory not accountable for by dementia severity. The PD group did not differ from the control group in remote memory, despite anterograde memory impairment. These results support the position that different component processes characterize remote memory, various mnemonic and nonmnemonic cognitive processes contribute to remote memory performance, and anterograde and remote memory processes are dissociable and differentially disrupted by neurodegenerative disease.

  View details for DOI 10.1037//0894-4105.14.2.265

  View details for Web of Science ID 000087480700010

  View details for PubMedID 10791866

• Relationship of CogScreen-AE to flight simulator performance and pilot age AVIATION SPACE AND ENVIRONMENTAL MEDICINE Taylor, J. L., O'Hara, R., Mumenthaler, M. S., Yesavage, J. A. 2000; 71 (4): 373-380

  Abstract

  We report on the relationship between CogScreen-Aeromedical Edition (AE) factor scores and flight simulator performance in aircraft pilots aged 50-69.Some 100 licensed, civilian aviators (average age 58+/-5.3 yr) performed aviation tasks in a Frasca model 141 flight simulator and the CogScreen-AE battery. The aviation performance indices were: a) staying on course; b) dialing in communication frequencies; c) avoiding conflicting traffic; d) monitoring cockpit instruments; e) executing the approach; and f) a summary score, which was the mean of these scores. The CogScreen predictors were based on a factor structure reported by Kay (11), which comprised 28 CogScreen scores. Through principal components analysis of Kay's nine factors, we reduced the number of predictors to five composite CogScreen scores: Speed/Working Memory (WM), Visual Associative Memory, Motor Coordination, Tracking, and Attribute Identification.Speed/WM scores had the highest correlation with the flight summary score, Spearman r(rho) = 0.57. A stepwise-forward multiple regression analysis indicated that four CogScreen variables could explain 45% of the variance in flight summary scores. Significant predictors, in order of entry, were: Speed/WM, Visual Associative Memory, Motor Coordination, and Tracking (p<0.05). Pilot age was found to significantly improve prediction beyond that which could be predicted by the four cognitive variables. In addition, there was some evidence for specific ability relationships between certain flight component scores and CogScreen scores, such as approach performance and tracking errors.These data support the validity of CogScreen-AE as a cognitive battery that taps skills relevant to piloting.

  View details for Web of Science ID 000086061300002

  View details for PubMedID 10766461

• An actigraphic comparison of sleep restriction and sleep hygiene treatments for insomnia in older adults JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Friedman, L., Benson, K., Noda, A., Zarcone, V., Wicks, D. A., O'Connell, K., Brooks, J. O., Bliwise, D. L., Yesavage, J. A. 2000; 13 (1): 17-27

  Abstract

  We compared the efficacy of sleep restriction therapy combined with sleep hygiene, nap modification of sleep restriction therapy combined with sleep hygiene, and sleep hygiene alone as treatments for insomnia in 39 community-dwelling men and women 55 years and older. We used the wrist actigraph as an objective outcome measure for all subjects at baseline, end of treatment, and 3-month follow-up; polysomnography (PSG) was conducted in a subgroup of subjects. Although subjects appeared to follow restriction instructions through follow-up, we found few between-group differences in treatment efficacy. Lack of treatment effect might be explained by the efficacy of HYG as a treatment in itself and the relatively low symptom level in these healthy older poor sleepers. At baseline, actigraphic results were found to correlate more highly than sleep log data with PSG in our sample. Actigraphic total sleep time, in particular, was highly correlated with PSG.

  View details for Web of Science ID 000085979100003

  View details for PubMedID 10753003

• How can we learn about developmental processes from cross-sectional studies, or can we? AMERICAN JOURNAL OF PSYCHIATRY Kraemer, H. C., Yesavage, J. A., Taylor, J. L., Kupfer, D. 2000; 157 (2): 163-171

  Abstract

  Cross-sectional studies are often used in psychiatric research as a basis of longitudinal inferences about developmental or disease processes. While the limitations of such usage are often acknowledged, these are often understated. The authors describe how such inferences are often, and sometimes seriously, misleading.Why and how these inferences mislead are here demonstrated on an intuitive level, by using simulated data inspired by real problems in psychiatric research.Four factors with major roles in the relationship between cross-sectional studies and longitudinal inferences are selection of time scale, type of developmental process studied, reliability of measurement, and clarity of terminology. The authors suggest how to recognize inferential errors when they occur, describe how to protect against such errors in future research, and delineate the circumstances in which only longitudinal studies can answer crucial questions.The simple conclusion is that one must always use the results of cross-sectional studies to draw inferences about longitudinal processes with trepidation.

  View details for Web of Science ID 000085169000003

  View details for PubMedID 10671382

• Update on Alzheimer's disease: recent findings and treatments WESTERN JOURNAL OF MEDICINE O'Hara, R., Mumenthaler, M. S., Yesavage, J. A. 2000; 172 (2): 115-120

  View details for Web of Science ID 000085217100020

  View details for PubMedID 10693374

• alpha 2 macroglobulin and the risk of Alzheimer's disease NEUROLOGY Dodel, R. C., Du, Y., Bales, K. R., Gao, F., Eastwood, B., Glazier, B., Zimmer, R., Cordell, B., Hake, A., Evans, R., Gallagher-Thompson, D., Thompson, L. W., Tinklenberg, J. R., Pfefferbaum, A., SULLIVAN, E. V., Yesavage, J., Altstiel, L., Gasser, T., Farlow, M. R., Murphy, G. M., Paul, S. M. 2000; 54 (2): 438-442

  Abstract

  alpha2 Macroglobulin is a panproteinase inhibitor that is found immunohistochemically in neuritic plaques, a requisite neuropathologic feature of AD. Recently, a pentanucleotide deletion near the 5' end of the "bait region" of the alpha2 macroglobulin (A2M) gene was reported to be associated with AD in a large cohort of sibpairs, in which the mutation conferred a similar odds ratio with AD as the APOE-epsilon4 allele for carriers of at least one copy of the A2M gene (Mantel-Haenszel odds ratio, 3.56).We studied three independent association samples of AD patients (n = 309) with an age range of 50 to 94 years and representative controls (n = 281) to characterize the allele frequency of the pentanucleotide deletion in this cohort. We detected the mutation near the 5' splice site of exon 18 using standard PCR and restriction fragment length polymorphism methods. The results were adjusted for age, gender, education, and APOE polymorphism.We found that the A2M gene polymorphism conferred an increased risk for AD, with an estimated Mantel-Haenszel ratio of 1.5 (95% CI 1.1 to 2.2; p = 0.025). There was no age- or gender-dependent increase in A2M gene allele frequencies in AD patients compared with controls. The combined sample showed the expected association between AD and APOE-epsilon 4. In one of our three samples there was an interaction between the A2M and APOE-epsilon4 genes, but the other two samples showed no interaction between the two risk factors.Our data support an association between the A2M gene and AD. This association is less pronounced, however, in our cohort than in the previously reported sample of sibpairs.

  View details for Web of Science ID 000085043800030

  View details for PubMedID 10668709

• Structural brain correlates of verbal and nonverbal fluency measures in Alzheimer's disease 26th Annual Meeting of the International-Neuropsychological-Society Fama, R., Sullivan, E. V., Shear, P. K., Cahn-Weiner, D. A., Marsh, L., Lim, K. O., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. AMER PSYCHOLOGICAL ASSOC. 2000: 29–40

  Abstract

  This study examined the relationships between regional brain volumes and semantic, phonological, and nonverbal fluency in 32 participants with Alzheimer's disease (AD). Object but not animal semantic fluency correlated with frontal and temporal gray matter volumes. Phonological fluency was not significantly associated with any brain volume examined. Nonverbal fluency was selectively associated with bilateral frontal gray matter volumes. Hippocampal volumes, although markedly reduced in these patients, were not related to any of the fluency measures. Results lend evidence to the importance of the frontal lobes in the directed generation of nonverbal and verbal exemplars by AD patients. Furthermore, both left- and right-hemisphere regions contribute to the generation of verbal and nonverbal exemplars.

  View details for Web of Science ID 000085020000003

  View details for PubMedID 10674796

• Convergent behavioral and neuropsychological evidence for a distinction between identification and production forms of repetition priming JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL Gabrieli, J. D., Vaidya, C. J., Stone, M., Francis, W. S., Thompson-Schill, S. L., Fleischman, D. A., Tinklenberg, J. R., Yesavage, J. A., Wilson, R. S. 1999; 128 (4): 479-498

  Abstract

  Four experiments examined a distinction between kinds of repetition priming which involve either the identification of the form or meaning of a stimulus or the production of a response on the basis of a cue. Patients with Alzheimer's disease had intact priming on picture-naming and category-exemplar identification tasks and impaired priming on word-stem completion and category-exemplar production tasks. Division of study-phase attention in healthy participants reduced priming on word-stem completion and category-exemplar production tasks but not on picture-naming and category-exemplar identification tasks. The parallel dissociations in normal and abnormal memory cannot be explained by implicit-explicit or perceptual-conceptual distinctions but are explained by an identification-production distinction. There may be separable cognitive and neural bases for implicit modulation of identification and production forms of knowledge.

  View details for Web of Science ID 000084711800004

  View details for PubMedID 10650584

• The validation of the short form of the Geriatric Depression Scale (GDS) in Greece AGING CLINICAL AND EXPERIMENTAL RESEARCH Fountoulakis, K. N., Tsolaki, M., Iacovides, A., Yesavage, J., O'Hara, R., Kazis, A., Ierodiakonou, C. 1999; 11 (6): 367-372

  Abstract

  The Geriatric Depression Scale-15 (GDS-15) is a short, 15-item instrument specifically designed to assess depression in geriatric populations. Its items require a yes/no response. The Geriatric Depression Scale was first introduced by Yesavage et al. in 1983, and the short form (GDS-15) was developed by Sheikh and Yesavage in 1986. The aim of the current study was the standardization of the GDS-15 for use in Greece. Subjects were divided into Group A: 168 control subjects, and Group B: 103 patients suffering from clinically diagnosed depression. All were over 65 years of age. A score of 6/7 on the GDS-15 was found to be the best cut-off point for diagnosing depression in an elderly Greek population, with Sensitivity = 92.23 and Specificity = 95.24. GDS-15 manifests high internal consistency with Cronbach's alpha = 0.94, and all items seem to be equivalent. Factor Analysis of the GDS-15 revealed 4 factors: a cognitive (thought content), an affective, a functional, and a factor that reflects helplessness and fear for the future. The two diagnostic groups differed on all 4 factors scores at p-value <0.001.

  View details for Web of Science ID 000085695000004

  View details for PubMedID 10738851

• Dissociation between two forms of conceptual priming in Alzheimer's disease NEUROPSYCHOLOGY Vaidya, C. J., Gabrieli, J. D., Monti, L. A., Tinklenberg, J. R., Yesavage, J. A. 1999; 13 (4): 516-524

  Abstract

  Patients with Alzheimer's disease (AD) and healthy control participants performed 2 conceptual repetition priming tasks, word-associate production and category-exemplar production. Both tasks had identical study-phases of reading target words aloud, had the most common responses as target items, and required production of a single response. Patients with AD showed normal priming on word-associate production but impaired priming on category-exemplar production. This dissociation in AD suggests that conceptual priming is not a unitary form of memory but rather is mediated by separable memory systems.

  View details for Web of Science ID 000083035700005

  View details for PubMedID 10527059

• Brain structural and cognitive correlates of clock drawing performance in Alzheimer's disease 26th Annual Meeting of the International-Neuropsychological-Society Cahn-Weiner, D. A., SULLIVAN, E. V., Shear, P. K., Fama, R., Lim, K. O., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. CAMBRIDGE UNIV PRESS. 1999: 502–9

  Abstract

  The Clock Drawing Test (CDT) is widely used in the assessment of dementia and is known to be sensitive to the detection of deficits in neurodegenerative disorders such as Alzheimer's disease (AD). CDT performance is dependent not only on visuospatial and constructional abilities, but also on conceptual and executive functioning; therefore, it is likely to be mediated by multiple brain regions. The purpose of the present study was to identify component cognitive processes and regional cortical volumes that contribute to CDT performance in AD. In 29 patients with probable AD, CDT performance was significantly related to right-, but not left-hemisphere, regional gray matter volume. Specifically, CDT score correlated significantly with the right anterior and posterior superior temporal lobe volumes. CDT scores showed significant relationships with tests of semantic knowledge, executive function, and visuoconstruction, and receptive language. These results suggest that in AD patients, CDT performance is attributable to impairment in multiple cognitive domains but is related specifically to regional volume loss of right temporal cortex.

  View details for Web of Science ID 000083339700003

  View details for PubMedID 10561930

• Predicting response of older adults to mnemonic training: who will benefit? International psychogeriatrics MCKITRICK, L. A., Friedman, L. F., Brooks, J. O., Pearman, A., Kraemer, H. C., Yesavage, J. A. 1999; 11 (3): 289-300

  Abstract

  To identify profiles of subjects who respond to mnemonic training for serial word and proper name recall.Analysis of J. O. Brooks et al.'s (1999) mnemonic training data using Quality Receiver Operating Characteristic (QROC) and longitudinal regression analyses (LRA).Community.224 community-dwelling adults 55 years of age and older who wished to improve their memory.Performance on serial word and proper name tests; performance on cognitive ability tests.Although the QROC and LRA identified several common predictors (baseline performance, mental rotation ability, and paired associate learning), the QROC identified additional predictors and cognitive ability profiles associated with successful response.Similar degrees of response to mnemonic training are associated with heterogeneous cognitive profiles. This finding highlights the fact that participants rely on a variety of abilities to derive benefit from mnemonic training and thus suggests different avenues from which to approach this training.

  View details for PubMedID 10547129

• Relationship of age and simulated flight performance JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yesavage, J. A., Taylor, J. L., Mumenthaler, M. S., Noda, A., O'Hara, R. 1999; 47 (7): 819-823

  Abstract

  To determine the relationship between age and aviator performance on a flight simulator.A cross-sectional observational study.The sample consisted of 100 aviators aged 50 to 69 (mean = 58).Pilots were tested on a Frasca 141 flight simulator (Urbana, IL), linked to a UNIX-based IRIS 4D computer (Silicon Graphics, Mountain View, CA), which both generated graphics of the environment in which the pilots flew and collected data concerning the aircraft's flight conditions.We found that increased age was significantly associated with decreased aviator performance on a flight simulator.Although there was a significant relationship between increased age and decreased aviator performance, age explained 22% or less of the variance of performance on different flight tasks; hence, other factors are also important in explaining the performance of older pilots.

  View details for Web of Science ID 000081323400007

  View details for PubMedID 10404925

• Taking account of between-patient variability when modeling decline in Alzheimer's disease AMERICAN JOURNAL OF EPIDEMIOLOGY Joseph, L., Wolfson, D. B., Belisle, P., Brooks, J. O., Mortimer, J. A., Tinklenberg, J. R., Yesavage, J. A. 1999; 149 (10): 963-973

  Abstract

  The pattern of deterioration in patients with Alzheimer's disease is highly variable within a given population. With recent speculation that the apolipoprotein E allele may influence rate of decline and claims that certain drugs may slow the course of the disease, there is a compelling need for sound statistical methodology to address these questions. Current statistical methods for describing decline do not adequately take into account between-patient variability and possible floor and/or ceiling effects in the scale measuring decline, and they fail to allow for uncertainty in disease onset. In this paper, the authors analyze longitudinal Mini-Mental State Examination scores from two groups of Alzheimer's disease subjects from Palo Alto, California, and Minneapolis, Minnesota, in 1981-1993 and 1986-1988, respectively. A Bayesian hierarchical model is introduced as an elegant means of simultaneously overcoming all of the difficulties referred to above.

  View details for Web of Science ID 000080305200010

  View details for PubMedID 10342806

• Mnemonic training in older adults: effects of age, length of training, and type of cognitive pretraining. International psychogeriatrics Brooks, J. O., Friedman, L., Pearman, A. M., Gray, C., Yesavage, J. A. 1999; 11 (1): 75-84

  Abstract

  To improve performance with mnemonic techniques for remembering words and proper names.For word recall, a 2 x 2 factorial in which type of pretraining and length of training were between-subjects manipulations. For proper name recall, a two-group design in which type of pretraining was manipulated between subjects.Community.268 community-dwelling adults over the age of 55 years who wished to improve their memory.Recall of words and proper names both before and after training in mnemonics.Participants received a 2-week training course on two mnemonic techniques, the method of loci for words and a name association technique for proper names.There was no effect of the pretraining manipulation on proper name recall. For word recall, however, a multiple regression that included age indicated that the older-old participants benefited more from a combination of comprehensive pretraining and extended mnemonic training than did the younger-old.Increased training time coupled with a comprehensive pretraining regimen can improve the performance of the older-old in using mnemonics; this improved performance cannot be attributed solely to enhanced knowledge of the mnemonic.

  View details for PubMedID 10189601

• How to drastically reduce priming in word stem completion and still present the words MEMORY & COGNITION Brooks, J. O., Gibson, J. M., Friedman, L., Yesavage, J. A. 1999; 27 (2): 208-219

  Abstract

  This paper describes a series of experiments in which we demonstrated that "dysphonemic" word stems, which are likely not pronounced in isolation as they are within a word (e.g., MUS in MUSHROOM or LEG in LEGEND), showed less priming than did "phonemic stems" (e.g., MUS in MUSTARD or LEG in LEGACY). Furthermore, words with either dysphonemic or phonemic three-letter stems gave rise to equivalent levels of priming when test cues were four-letter stems (LEGE) or word fragments (L_G_ND). Moreover, the difference between phonemic and dysphonemic stems persisted when nonpresented completion rates were matched. A final cued-recall experiment revealed that performance was greater for phonemic stems than for dysphonemic stems and that this difference was greater for older participants than for younger ones. These results are not readily accounted for by extant theoretical approaches and point to important methodological issues regarding stem completion.

  View details for Web of Science ID 000079821600002

  View details for PubMedID 10226432

• Geriatric performance on the Benton visual retention test: demographic and diagnostic considerations CLINICAL NEUROPSYCHOLOGIST Coman, E., Moses, J. A., Kraemer, H. C., Friedman, L., Benton, A. L., Yesavage, J. 1999; 13 (1): 66-77

  Abstract

  We examined relationships between demographic and diagnostic variables and Benton Visual Retention Test performance in older adults aged 55 to 97 years. We derived extended geriatric norms for BVRT total number correct scores adjusted for variables that contributed significantly to the variance. We also investigated BVRT performance in two commonly presenting diagnostic groups: (1) normal adults with memory concerns, and (2) a group with mixed neurologic disorders. Age and education but not gender were significantly associated with BVRT performance in both normals and normals with memory concerns. Level of cognitive deficit was a moderating factor in that age and education also contributed significantly to the BVRT performance of no/low deficit neurologic patients but had no impact in patients whose cognitive deficits were moderate/severe.

  View details for Web of Science ID 000082002000007

  View details for PubMedID 10937649

• Effects of menstrual cycle and female sex steroids on ethanol pharmacokinetics ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Mumenthaler, M. S., Taylor, J. L., O'Hara, R., Fisch, H. U., Yesavage, J. A. 1999; 23 (2): 250-255

  Abstract

  This study investigated the influence of menstrual cycle and female sex steroid levels on ethanol pharmacokinetics. In a within-subjects design, 24 female volunteers each consumed 0.67 g x kg(-1) ethanol during the menstrual and luteal phases of their menstrual cycle. On each test day, we collected blood samples before ethanol administration to determine estradiol (E2) and progesterone (P) levels and to confirm ovulation. We took 20 or more postdrink breath ethanol concentration readings and examined pharmacokinetic differences between the two phases, using classical pharmacokinetic measures, as well as Michaelis-Menten measures. Despite highly significant differences in measured E2 as well as P levels on the 2 test days, and despite excluding subjects with anovulatory cycles from the analysis, there were no significant differences between menstrual and luteal phases for any of the pharmacokinetic variables. We found no correlation between E2 or P levels and any of the pharmacokinetic measures. In summary, we found no evidence that the tested menstrual cycle phases or varying E2 and progesterone levels significantly influence ethanol pharmacokinetics. Because previous studies about the topic have used few subjects and revealed controversial results, we consider our negative findings based on 24 subjects meaningful.

  View details for Web of Science ID 000078678700009

  View details for PubMedID 10069553

• Gender differences in moderate drinking effects ALCOHOL RESEARCH & HEALTH Mumenthaler, M. S., Taylor, J. L., O'Hara, R., Yesavage, J. A. 1999; 23 (1): 55-?

  Abstract

  Women appear to become more impaired than men after drinking equivalent amounts of alcohol, achieving higher blood alcohol concentrations even when doses are adjusted for body weight. This finding may be attributable in part to gender differences in total body water content. Men and women appear to eliminate approximately the same total amount of alcohol per unit body weight per hour. However, women seem to eliminate significantly more alcohol per unit of lean body mass per hour than men. Some studies report that women are more susceptible than men to alcohol-related impairment of cognitive performance, especially in tasks involving delayed memory or divided attention functions. Psychomotor performance impairment, however, does not appear to be affected by gender. This article provides an overview of alcohol metabolism (pharmacokinetics) and reviews recent studies on gender differences in alcohol absorption, distribution, elimination, and impairment. Speculation that gender differences in alcohol pharmacokinetics or alcohol-induced performance impairment may be caused by the menstrual cycle and variations in female sex hormones are discussed. It is concluded that the menstrual cycle is unlikely to influence alcohol pharmacokinetics.

  View details for Web of Science ID 000084105600008

  View details for PubMedID 10890798

• The APOE epsilon 4 allele is associated with decline on delayed recall performance in community-dwelling older adults JOURNAL OF THE AMERICAN GERIATRICS SOCIETY O'Hara, R., Yesavage, J. A., Kraemer, H. C., Mauricio, M., Friedman, L. F., Murphy, G. M. 1998; 46 (12): 1493-1498

  Abstract

  This study investigated whether the Apolipoprotein (APOE) epsilon4 allele was associated with cognitive decline in community-dwelling older adults.Longitudinal cognitive performance of older adults with the epsilon3/epsilon4 genotype was compared with that of older adults with the epsilon3/epsilon3 genotype.Aging Clinical Research Center, Stanford University.One hundred community-dwelling older adults were recruited from a pool of 531 individuals who had participated in a memory training study 4 to 5 years earlier. These individuals were concerned about their memory functioning and were recruited through newspaper advertisements and contacts with local senior centers. The 100 individuals who agreed to participate in the follow-up investigation were between 59 and 95 years of age.At both baseline and follow-up, subjects were administered a battery of seven cognitive tests that examined verbal and spatial memory, attention, speed-of-processing, and language abilities. APOE genotype was determined at follow-up.Individuals with the epsilon3/epsilon4 APOE genotype were significantly younger than individuals with the APOE epsilon3/epsilon3 genotype. No significant differences were observed between the two groups on measures of attention, speed-of-processing, vocabulary, immediate verbal memory, and immediate spatial memory. However, those older adults with the epsilon3/epsilon4 genotype exhibited significantly greater decline in performance on delayed recall of verbal material than did those with the epsilon3/epsilon3 APOE genotype.These findings are consistent with previous studies, which suggest that the APOE epsilon4 allele predicts decline on measures of delayed recall.

  View details for Web of Science ID 000077358700001

  View details for PubMedID 9848808

• The stages of Alzheimer's disease: A reappraisal DEMENTIA AND GERIATRIC COGNITIVE DISORDERS Kraemer, H. C., Taylor, J. L., Tinklenberg, J. R., Yesavage, J. A. 1998; 9 (6): 299-308

  Abstract

  'Stages', as used in clinical practice and research, are defined, their value described, and criteria are proposed for their evaluation. The specific interest is in staging Alzheimer's disease (AD). Two staging systems, one based on the Global Deterioration Scale (GDS) and one based on the Mini-Mental State Exam (MMSE), are compared in terms of these criteria, as an illustration of the process involved. We propose that there is not one unique staging system, that different staging criteria might be appropriate to different research or clinical needs, depending on which part of the temporal course of the disease is of primary interest, and on whether the focus is on cognitive, functional, neurological, behavioral, economic, or other issues. GDS staging seems a better choice for the later stages of AD when the focus is on functional change. MMSE staging seems a better choice for tracking the earlier stages of AD when the focus is on cognitive change.

  View details for Web of Science ID 000076711600001

  View details for PubMedID 9769442

• Influence of nicotine on simulator flight performance in non smokers PSYCHOPHARMACOLOGY Mumenthaler, M. S., Taylor, J. L., O'Hara, R., Yesavage, J. A. 1998; 140 (1): 38-41

  Abstract

  In a placebo-controlled study, we investigated the influence of nicotine on late-day aviation performance in 15 non-smoking subjects. In a within-subjects design, subjects were tested on 2 days, each lasting 8 h and consisting of three 75-min simulator flights (late-afternoon practice, evening test, night test). Prior to each test, subjects received either nicotine polacrilex 2 mg or placebo gum. As expected, overall performance was significantly better after nicotine, compared to placebo (P < 0.01). Post-hoc analysis of individual flight tasks showed that nicotine improved scores on approach to landing, a task which appears to require sustained attention. We conclude that nicotine may improve late-day flight performance in non-smoking aviators.

  View details for Web of Science ID 000077151700005

  View details for PubMedID 9862400

• Fluency performance patterns in Alzheimer's disease and Parkinson's disease CLINICAL NEUROPSYCHOLOGIST Fama, R., Sullivan, E. V., Shear, P. K., Cahn-Weiner, D. A., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. 1998; 12 (4): 487-499

  View details for Web of Science ID 000080699400005

• Everyday problem solving among individuals with Alzheimer's disease GERONTOLOGIST Willis, S. L., Allen-Burge, R., Dolan, M. M., Bertrand, R. M., Yesavage, J., Taylor, J. L. 1998; 38 (5): 569-577

  Abstract

  Loss of functioning on complex tasks of daily living is an early indicator of dementia. The performance of 65 older adults with mild to moderate levels of Alzheimer's disease was examined on the Everyday Problems Test for the Cognitively Challenged Elderly (EPCCE), self-report inventories of functional performance, and a broad battery of clinical and neuropsychological measures. The EPCCE was designed to assess older adults on a set of complex tasks of daily living that involved not only global cognitive processes, but also higher-order executive functions. Participants solved an average of 45% of EPCCE tasks with significant differences in scores by disease severity. Performance was significantly related to global cognitive functioning and disease severity, and in particular to executive functions. Significant additional variance was accounted for by these executive functions beyond the variance accounted for by global cognitive measures.

  View details for Web of Science ID 000076643900005

  View details for PubMedID 9803645

• Preserved priming across study-test picture transformations in patients with Alzheimer's disease NEUROPSYCHOLOGY Park, S. M., Gabrieli, J. D., Reminger, S. L., Monti, L. A., Fleischman, D. A., Wilson, R. S., Tinklenberg, J. R., Yesavage, J. A. 1998; 12 (3): 340-352

  Abstract

  Picture-naming priming was examined across different study-test transformations to explore the nature of memory representations of objects supporting implicit memory processes in patients with Alzheimer's disease (AD). Although severely impaired in explicit memory for pictures and words, AD patients demonstrated normal priming across perceptual transformations in picture orientation (Experiment 1) and picture size (Experiment 2) and across symbolic transformations from words to pictures (Experiment 3). In addition, the priming across alterations in picture size was invariant. This demonstrates that AD patients have preserved implicit memory for high-level, abstract representations of objects.

  View details for Web of Science ID 000074744800002

  View details for PubMedID 9673992

• Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach. International psychogeriatrics Brooks, J. O., Yesavage, J. A., Carta, A., Bravi, D. 1998; 10 (2): 193-203

  Abstract

  To assess the longitudinal effects of acety-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease.Longitudinal, double-blind, parallel-group, placebo-controlled.Twenty-four outpatient sites across the United States.A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996).Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year.The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age x Drug interaction characterized by younger subjects benefiting more from ALC, significant, cutpoint for ALC benefit was 61 years of age.ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.

  View details for PubMedID 9677506

• Effects of human growth hormone, insulin-like growth factor I, and diet and exercise on body composition of obese postmenopausal women JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Thompson, J. L., Butterfield, G. E., Gylfadottir, U. K., Yesavage, J., Marcus, R., Hintz, R. L., Pearman, A., Hoffman, A. R. 1998; 83 (5): 1477-1484

  Abstract

  To determine the effects of GH and insulin-like growth factor I (IGF-I) administration, diet, and exercise on weight loss, body composition, basal metabolic rate (BMR), muscle strength, and psychological status, 33 moderately obese postmenopausal women (67.1 +/- 5.2 yr) participated in a 12-week randomized, double blind study. Participants were placed on a diet that provided 500 Cal/day less than that needed for weight maintenance, and they walked 3 days and strength trained 2 days each week. Subjects also self-injected GH (0.025 mg/kg BW.day), IGF-I (0.015 mg/kg BW.day), a combination of these doses of GH and IGF-I, or placebo (P). Twenty-eight women completed the study, as five subjects dropped out due to intolerable side-effects (e.g. edema). Weight loss occurred in all groups, with the largest decrease occurring in the GH plus IGF-I group (5.6 +/- 1.4 kg). Fat mass significantly decreased in all groups, with the largest losses observed in GH and GH plus IGF-I groups (6.3 +/- 1.8 and 8.4 +/- 2.8 kg, respectively). Despite weight loss, BMR was maintained in all groups. Muscle strength increased with training for all groups, and depression and anxiety scores decreased in groups receiving IGF-I. These data show that obese postmenopausal women can lose weight and fat without compromising fat free mass, BMR, or gains in muscle strength, and that GH and IGF-I given together may enhance fat loss over either given alone.

  View details for Web of Science ID 000073535300013

  View details for PubMedID 9589642

• Patterns of brain volume abnormalities in Alzheimer's disease Pfefferbaum, A., SULLIVAN, E. V., Mathalon, D. H., Yesavage, J. A., Tinklenberg, J. R., Lim, K. O. ELSEVIER SCIENCE INC. 1998: 23S–24S

  View details for Web of Science ID 000073240700078

• A follow-up study of actigraphic measures in home-residing Alzheimer's disease patients JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Yesavage, J. A., Friedman, L., Kraemer, H. C., Noda, A., Wicks, D., Bliwise, D. L., Sheikh, J., Tinklenberg, J., Zarcone, V. 1998; 11 (1): 7-10

  Abstract

  This article reports cross-sectional and follow-up data with actigraphic measures of nocturnal sleep and rest/activity in 61 Alzheimer's disease (AD) patients as well as the relation of actigraphic measures to levels of behavioral disturbance across different stages of the disease. Over the course of approximately 1.5 years' follow-up, patients showed significant deterioration of nocturnal sleep parameters, but no significant change in rest/activity circadian rhythm parameters. There were also significant correlations among nocturnal sleep, rest/activity circadian rhythm, and behavioral disturbance measures, but only in relatively early stages of AD. It is argued that study of nocturnal sleep and circadian rhythm in relation to behavioral disturbance in AD requires longitudinal data and analyses that take into account the stage of disease at which patients are assessed.

  View details for Web of Science ID 000074755600002

  View details for PubMedID 9686746

• N400 evidence for picture naming difficulty Ford, J. M., Askari, N., Hoffman, J. R., Wu, J. J., Yesavage, J., Tinklenberg, J. R., Gabrieli, J. MIT PRESS. 1998: 33–33

  View details for Web of Science ID 000073196500091

• Adjusting Mini-Mental State Examination scores for age and educational level to screen for dementia: correcting bias or reducing validity? International psychogeriatrics Kraemer, H. C., MORITZ, D. J., Yesavage, J. 1998; 10 (1): 43-51

  Abstract

  The question of whether Mini-Mental State Examination scores should be adjusted for age and educational levels to screen for dementia in clinical populations is reexamined in the results of a recent study supporting adjustment. If the criterion is to identify the most accurate screening procedure for each sociodemographic subgroup, the evidence indicates that the unadjusted scores are preferable. Other criteria might lead to different conclusions. The validities of some of these criteria are questionable because they have the flaw that they are easily satisfied by using random decision procedures.

  View details for PubMedID 9629523

• Cognitive and noncognitive symptoms in dementia patients: relationship to cortisol and dehydroepiandrosterone. International psychogeriatrics MILLER, T. P., Taylor, J., Rogerson, S., Mauricio, M., Kennedy, Q., Schatzberg, A., Tinklenberg, J., Yesavage, J. 1998; 10 (1): 85-96

  Abstract

  We investigated the relationship between basal cortisol and dehydroepiandrosterone (DHEA) levels and impairment in different cognitive and noncognitive measures and the possible interaction of DHEA with hypercortisolemia in dementia in 27 patients diagnosed with Alzheimer's disease (AD). There were 17 men and 10 women. Patients were mildly to moderately cognitively impaired at the time of the initial cortisol measures. Patients were administered the Alzheimer's Disease Assessment Scale (ADAS) and Folstein Mini-Mental State Examination (MMSE) at approximately 6-month intervals. Cortisol and DHEA were determined using conventional 125I radioimmunoassay procedures. Pearson product-moment correlations among cortisol and DHEA measures and both initial and longitudinal clinical measures were calculated. There was a relationship between baseline 8 a.m. cortisol levels and cognitive function at the initial testing as measured by the ADAS cognitive measure, with higher cortisol levels being associated with a greater level of impairment. We did not document a relationship between cortisol or DHEA levels and noncognitive measures. There was a significant correlation between both the initial MMSE and ADAS cognitive measures and initial DHEA level, with lower DHEA levels unexpectedly being associated with better performance on these measures. The initial DHEA levels did not predict decline in cognitive function over time. These findings bring into question the potential usefulness of DHEA as a therapeutic agent.

  View details for PubMedID 9629527

• Advantages of excluding underpowered studies in meta-analysis: Inclusionist versus exclusionist viewpoints PSYCHOLOGICAL METHODS Kraemer, H. C., Gardner, C., Brooks, J. O., Yesavage, J. A. 1998; 3 (1): 23-31

  View details for Web of Science ID 000072410000002

• Structural MRI correlates of recognition memory in Alzheimer's disease JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY Cahn, D. A., SULLIVAN, E. V., Shear, P. K., Marsh, L., Fama, R., Lim, K. O., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. 1998; 4 (2): 106-114

  Abstract

  Neuroimaging and lesion studies have demonstrated that hippocampal volume correlates with memory performance, but material-specific lateralization of this structure-function relationship has been inconsistent. This MRI study examined the relative contributions of left and right temporal lobe volumes to verbal and nonverbal recognition memory in a group of 20 Alzheimer's disease (AD) patients. There was a significant relationship between extent of right hippocampal and right temporal gray matter tissue volume deficit and performance on the face recognition subtest of the Warrington Recognition Memory Test. The face recognition test correlated with right hemisphere volume but not to left, indicating a material-specific relationship between brain structure and function in this patient group. Right temporal horn volume did not account for a significant proportion of variance in face recognition memory. Although word recognition was not significantly correlated with either left or right hippocampal volume in the total group, there was a strong correlation between left hippocampal volume and word recognition memory in the female AD patients. Thus, face recognition shows a material specific relationship with select lateralized hippocampal and temporal cortical volumes in AD patients, regardless of gender, whereas the verbal recognition-left-hippocampal volume relationship may be mediated by gender.

  View details for Web of Science ID 000075146200002

  View details for PubMedID 9529820

• Selective cortical and hippocampal volume correlates of Mattis Dementia Rating Scale in Alzheimer disease Annual Meeting of the International-Neuropsychological-Society Fama, R., SULLIVAN, E. V., Shear, P. K., Marsh, L., Yesavage, J. A., Tinklenberg, J. R., Lim, K. O., Pfefferbaum, A. AMER MEDICAL ASSOC. 1997: 719–28

  Abstract

  To examine whether each of the 5 Mattis Dementia Rating Scale (DRS) scores related to magnetic resonance imaging-derived volumes of specific cortical or limbic brain regions in patients with Alzheimer disease (AD).Relations between DRS measures and regional brain volume measures were tested with bivariate and multivariate regression analyses.The Aging Clinical Research Center of the Stanford (Calif) University Department of Psychiatry and Behavioral Science and the Geriatric Psychiatry Rehabilitation Unit of the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif.Fifty patients with possible or probable AD. Magnetic resonance imaging data from 136 healthy control participants, age 20 to 84 years, were used to correct brain volumes for normal variation arising from intracranial volume and age.The DRS scores and volumes of regional cortical gray matter and of the hippocampus.Memory scores of the patients with AD were selectively related to hippocampal volumes. Attention and construction scores were related to several anterior brain volume measures, with attention showing a significantly greater association to right than left hemisphere measures. Initiation/perseveration scores were not significantly correlated with any measure of regional gray matter volume, but performance was related to prefrontal sulcal widening, with a greater association with the left than right sulcal volume.Certain DRS subtests are predictably correlated with selective regional brain volumes in AD. The specific relation between memory and hippocampal volumes and the nonsignificant relations between memory and regional cortical volumes suggest a dissociation between cortical and hippocampal contributions to explicit memory performance.

  View details for Web of Science ID A1997XE00100008

  View details for PubMedID 9193207

• Cognitive function and the costs of Alzheimer disease - An exploratory study ARCHIVES OF NEUROLOGY Ernst, R. L., Hay, J. W., Fenn, C., Tinklenberg, J., Yesavage, J. A. 1997; 54 (6): 687-693

  Abstract

  To estimate the dollar savings in costs attainable from drug or other treatments for Alzheimer disease (AD) that stabilize or reverse patients' cognitive decline.Medical and other disease-related utilization data were collected from the caregivers of 64 patients diagnosed as having probable AD. The quantities of utilization were priced at national levels to generate measures of illness costs. Costs per patient were then estimated as regression functions of scores on the Mini-Mental State Examination (MMSE), which was used as an index of patient cognitive function. Potential savings in illness costs were estimated by comparing predicted costs at various baseline and intervention-level values of the patient's MMSE score.The potential savings in illness costs attainable from treatment are small for mildly and very severely demented patients with AD. However, for moderately to severely demented home-dwelling patients having, say, an MMSE score of 7 at baseline, prevention of a 2-point decline in the score would save about $3700 annually, and a 2-point increase in an MMSE score rather than a 2-point decline would save about $7100.Large savings in the costs of caring for moderately to severely demented home-dwelling patients with AD may be achievable from disease interventions that have minor effects on patients' cognitive status.

  View details for Web of Science ID A1997XE00100004

  View details for PubMedID 9193203

• No association between apolipoprotein E epsilon 4 allele and rate of decline in Alzheimer's disease AMERICAN JOURNAL OF PSYCHIATRY Murphy, G. M., Taylor, J., Kraemer, H. C., Yesavage, J., Tinklenberg, J. R. 1997; 154 (5): 603-608

  Abstract

  The relationship between number of apolipoprotein E epsilon 4 (APOE epsilon 4) alleles and the rate of cognitive decline in patients with Alzheimer's disease was examined.Rate of decline in score on the Mini-Mental State was measured during the active phase of the decline curve between Mini-Mental State scores of 23 and 0. To characterize onset, the authors also estimated for each subject the age at which the Mini-Mental State score fell below 23 and obtained a retrospective report of age at onset from the caregiver. The number of APOE epsilon 4 alleles carried by each subject was determined from genomic DNA samples. The study included 86 subjects with probable Alzheimer's disease who had had at least two cognitive evaluations (a mean of 5.6 evaluations per subject over an average period of 3.6 years).The results did not support an association between APOE epsilon 4 dosage and rate of cognitive decline. Age at onset and age at which the Mini-Mental State score fell below 23 were also not related to APOE epsilon 4 dosage. The APOE allele frequencies were similar to those in other studies of subjects with Alzheimer's disease, showing an enrichment of the epsilon 4 allele.Although the APOE epsilon 4 allele is a risk factor for Alzheimer's disease, there is no support of a strong association between APOE epsilon 4 dosage and rate of cognitive decline. The epsilon 4 allele did not predict age at onset. Methodological inconsistencies may account for discrepancies between these results and previous findings.

  View details for Web of Science ID A1997WX13000004

  View details for PubMedID 9137113

• No association between the alpha 1-antichymotrypsin A allele and Alzheimer's disease NEUROLOGY Murphy, G. M., SULLIVAN, E. V., GALLAGHERTHOMPSON, D., Thompson, L. W., vanDuijn, C. M., Forno, L. S., Ellis, W. G., Jagust, W. J., Yesavage, J., Tinklenberg, J. R. 1997; 48 (5): 1313-1316

  Abstract

  The alpha 1-antichymotrypsin (ACT) A allele was recently associated with Alzheimer's disease (AD), and the ACT AA genotype was reported to be more frequent in AD subjects with the apolipoprotein E (APOE) epsilon4 allele. We examined ACT and APOE genotypes in a sample of 160 subjects with probable AD and in 102 elderly control subjects. ACT A allele frequencies were similar in AD subjects (0.503) and elderly controls (0.519). In addition, we found no evidence that in AD the AA genotype is more frequent in subjects with the APOE epsilon4 allele than in those without it. Our results do not support an association between the ACT A allele and AD.

  View details for Web of Science ID A1997WZ77800030

  View details for PubMedID 9153464

• Disruptive behavior and actigraphic measures in home-dwelling patients with Alzheimer's disease: Preliminary report JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Friedman, L., Kraemer, H. C., Zarcone, V., Sage, S., Wicks, D., Bliwise, D. L., Sheikh, J., Tinklenberg, J., Yesavage, J. A. 1997; 10 (2): 58-62

  Abstract

  The purpose of this preliminary report was to explore overall level and diurnal patterning of caregiver reports of abnormal behavior and to explore relationships with actigraphic measures of sleep/wake activity in Alzheimer's disease (AD) patients. Our primary behavioral measure was the Time-based Behavioral Disturbance Questionnaire (TBDQ). The overall score on this measure was shown to have adequate test-retest reliability and convergent validity with another behavioral measure. Significant correlations were obtained between the TBDQ overall score and actigraphically scored sleep efficiency (r = -.35, P < .05) and wake after sleep onset (r = .43, P < .01) in 41 subjects. The data suggest a moderate relationship between actigraphic measures of sleep/wake and disturbed behavior in home-dwelling AD patients.

  View details for Web of Science ID A1997XC89900004

  View details for PubMedID 9188020

• Assessment and Management of "Sundowning" Phenomena. Seminars in clinical neuropsychiatry Taylor, Friedman, Sheikh, Yesavage 1997; 2 (2): 113-122

  Abstract

  Approximately one quarter of patients with AD-type dementia reportedly exhibit disruptive, restless, and/or confused behavior that tends to be more apparent in late afternoon or early evening. Research has yet to document the phenomenon in a definitive manner to facilitate standardized assessment and clinical trials. Recent work attempting to define precisely the prevalence of abnormal behaviors during different periods of time of day in AD patients is reviewed. Caregiver reports of confusion and aggressive, disruptive behavior have been associated with going to bed early, increased use of sedative-hypnotics, and more severe cognitive impairment. Because there is evidence that the sleep of many AD patients is of poor quality, one might try to treat such patients with behavioral approaches useful in insomnia in other populations. Futhermore, as psychotropic medications can adversely affect sleep and/or have "hangover" effects on daytime cognition, one should carefully manage these medications to optimize care. Advances in assessment of sundowning, combined with longitudinal studies of sleep and circadian rhythm changes associated with dementia progression, should enhance efforts to treat behavioral and sleep disturbances.

  View details for PubMedID 10320451

• Automatic and effortful processing in aging and dementia: Event-related brain potentials NEUROBIOLOGY OF AGING Ford, J. M., Roth, W. T., Isaacks, B. G., Tinklenberg, J. R., Yesavage, J., Pfefferbaum, A. 1997; 18 (2): 169-180

  Abstract

  Automatic and effortful processes were investigated using event-related brain potentials (ERPs) recorded from moderately impaired subjects with probable Alzheimer's Disease (AD), normal elderly, and normal young controls. The effects of effortful attention on ERPs to loud noises and the effects of stimulus intrusiveness on effortfully elicited ERPs were studied. First, ERPs to task relevant and irrelevant startling noises were compared. Second, ERPs to startling noises and moderate tones were compared when both were targets. The effects of age (young vs. elderly controls) and effects of dementing disease (AD subjects vs. elderly controls) were also assessed. Effortful attention augmented noise-elicited P300 amplitude in elderly subjects, but not in young. Intrusiveness augmented task-relevant P300 amplitude in young subjects, but not in elderly. Neither variable affected P300 amplitude in AD subjects. Thus, effects of age and disease depended on how P300 was elicited: when effortfully elicited, P300 amplitude was affected by disease but not age; when automatically elicited, P300 amplitude was affected by age but not disease. N1 effects differed from P300 effects.

  View details for Web of Science ID A1997XP01300006

  View details for PubMedID 9258894

• The apolipoprotein E epsilon 4 allele is associated with increased behavioral disturbance in Alzheimer's disease AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Murphy, G. M., Taylor, J., Tinklenberg, J. R., Yesavage, J. A. 1997; 5 (1): 88-89

  View details for Web of Science ID A1997VZ64200012

  View details for PubMedID 9169250

• Measuring behavior, mood, and psychiatric symptoms in Alzheimer disease Teri, L., Logsdon, R., Yesavage, J. LIPPINCOTT WILLIAMS & WILKINS. 1997: 50–59

  Abstract

  Behavioral disturbances, psychiatric symptoms, and mood disorders are prevalent, persistent, and debilitating aspects of the clinical course of Alzheimer disease. The authors discuss the phenomenology of these problems, their importance in understanding disease course and planning treatment, and the current state-of-the-art methods for assessment. Issues to consider in assessment of these problems also are discussed.

  View details for Web of Science ID 000071204600008

  View details for PubMedID 9437448

• Rate of cognitive decline in Alzheimer's disease is not affected by the alpha-1-antichymotrypsin A allele or the CYP2D6 B mutant NEUROSCIENCE LETTERS Murphy, G. M., Yang, L., Yesavage, J., Tinklenberg, J. R. 1996; 217 (2-3): 200-202

  Abstract

  Patients with Alzheimer's disease (AD) show considerable heterogeneity in the rate at which they decline cognitively. The biological basis for this heterogeneity is unknown. We genotyped 86 subjects with diagnoses of probable AD to determine if they carried the alpha-1-antichymotrypsin (ACT) A allele, which has been associated with AD, or the CYP2D6 B mutant, found at increased frequency in the Lewy body variant (LBV) of AD. We then examined longitudinally-collected cognitive data to determine if these genetic markers were associated with rate of cognitive decline. Our results indicate that neither the ACT A allele nor the CYP2D6 B allele have a significant association with rate of decline on the Folstein Mini Mental State examination. Further, subjects with both the ACT A allele and the apolipoprotein epsilon 4 allele showed no evidence of accelerated decline. These findings suggest that any increased risk of developing AD or LBV conferred by these markers is not necessarily accompanied by a more rapid rate of decline.

  View details for Web of Science ID A1996VQ39800033

  View details for PubMedID 8916107

• N400 evidence of abnormal responses to speech in Alzheimer's disease ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Ford, J. M., Woodward, S. H., SULLIVAN, E. V., Isaacks, B. G., Tinklenberg, J. R., Yesavage, J. A., Roth, W. T. 1996; 99 (3): 235-246

  Abstract

  The status of semantic priming in Alzheimer's disease (AD) was examined using the speech elicited N400 component of the event-related brain potential (ERP). Speech was naturally paced, with 1 s of silence before the final word. In the semantic task, subjects attended to the meaning of the sentences for a subsequent memory test. In the phonemic monitoring task, they counted the words beginning with the letter 'p'. The effects of age were assessed by comparing young and elderly, and the effects of disease by comparing elderly and AD subjects. In healthy young and elderly subjects, N400s were large to semantically unprimed words and small to semantically primed words. In AD subjects, N400s were large to primed words, reflecting a failure of the sentence stem to prime the final word, and probably an impairment in semantic knowledge. The N400 priming effect was not smaller during the phonemic than semantic task in any group, suggesting that the semantic qualities of speech are processed even when subjects are attending to phonemic qualities. N400 latency was delayed with age and further delayed with dementia.

  View details for Web of Science ID A1996VL66900004

  View details for PubMedID 8862113

• Alcohol elimination and simulator performance of male and female aviators: A preliminary report AVIATION SPACE AND ENVIRONMENTAL MEDICINE Taylor, J. L., DOLHERT, N., Friedman, L., Mumenthaler, M., Yesavage, J. A. 1996; 67 (5): 407-413

  Abstract

  In this preliminary study of alcohol effects on aviators' flight simulator performance, we addressed some methodological issues regarding possible gender-related differences in response to alcohol.Subjects were 11 male and 12 female general aviation pilots, ages 21-40. Subjects received 8 h of training before they were tested with alcohol. On the alcohol test day they were tested before drinking, while intoxicated (target BAC of 0.08%), and 8 h after drinking.The average, observed peak BAC readings for men and women were within 0.003% of each other. We observed faster disappearance rates for women such that women reached the FAA cutoff of 0.04% approximately 1 h before men, on average. Compared to predrink performance, there was a significant decrement in simulator performance during acute intoxication, but not 8 h after drinking. There were no significant gender differences in performance before or after drinking alcohol. Slower rates of alcohol elimination were associated with larger performance changes 8 h after drinking. This is the first report to our knowledge suggesting a possible relation between alcohol elimination rate and change in performance after drinking alcohol.A 12.5% dose reduction for women appears to be adequate for achieving comparable peak BAC's for male and female groups. Future studies using measures of circadian rhythmicity in conjunction with pharmacokinetic and performance measures could potentially shed light on differences in subjects' acute and delayed responses to alcohol.

  View details for Web of Science ID A1996UH18500001

  View details for PubMedID 8725465

• Trends in pharmacotherapy of schizoaffective and bipolar affective disorders: A 5-year naturalistic study AMERICAN JOURNAL OF PSYCHIATRY FENN, H. H., Robinson, D., LUBY, V., Dangel, C., Buxton, E., Beattie, M., Kraemer, H., Yesavage, J. A. 1996; 153 (5): 711-713

  Abstract

  The authors' goal was to determine if the actual treatment of schizoaffective and bipolar affective disorders had changed in light of recent clinical drug trials that have suggested that valproate and carbamazepine may be equivalent in efficacy to lithium.Medication utilization rates for each 6-month period from July 1, 1989, to June 30, 1994, were compiled from the clinical database of the Palo Alto Veterans Affairs Medical Center. Results: The use of valproate and valproate plus lithium was negligible in 1989. by 1994, these medication regimens accounted for 25% of the standard antimanic treatments used for bipolar affective disorder and 38% of the treatments used for schizoaffective disorder. Regimens of carbamazepine and carbamazepine plus lithium dropped from 24% of antimanic treatments in 1989 to 18% in 1994. From 1989 to 1994, there was a decline in the rate of lithium monotherapy for treatment of bipolar affective disorder (from 84% to 43%) and schizoaffective disorder (from 100% to 53%).In the past 5 years, valproate monotherapy has increased as a percentage of total antimanic pharmacotherapies, while lithium monotherapy has declined.

  View details for Web of Science ID A1996UH92100021

  View details for PubMedID 8615421

• Dangerousness commitments: Indices of future violence potential? BULLETIN OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW ZEISS, R. A., Tanke, E. D., FENN, H. H., Yesavage, J. A. 1996; 24 (2): 247-253

  Abstract

  This study examines the accuracy of long-term clinical predictions of dangerousness among psychiatric inpatients and explores factors influencing the levels of such accuracy. Hospital and state criminal history records of all psychiatric patients (N = 31) for whom, during a four-year period, treatment staff pursued extended civil commitments based on dangerousness under the Postcertification for the imminently Dangerous statute (California Welfare and Institutions Code section 5300) were reviewed. A matched control group consisted of 31 patients who had been placed on 14-Day Certifications for Dangerousness to Others, but who were not subsequently placed on 180-Day Postcertifications. Sixty-one percent of patients in the postcertification group engaged in documented physically assaultive behavior during the extended one- to five-year follow-up period, compared with 26 percent of patients in the matched control group, suggesting that inclusion in the extended commitment group was indicative of greater long-term potential for assault. Differences in assaultiveness did not emerge during the first year of followup, but became clear and significant over subsequent years. Accuracy of prediction differed as a function of patient ethnic group.

  View details for Web of Science ID A1996UU93100009

  View details for PubMedID 8807164

• PERCEPTIONS OF LIFE STRESS AND CHRONIC INSOMNIA IN OLDER ADULTS PSYCHOLOGY AND AGING Friedman, L., Brooks, J. O., Bliwise, D. L., Yesavage, J. A., WICKS, D. S. 1995; 10 (3): 352-357

  Abstract

  This study compared the level of self-reported stress of 42 older good sleepers (M age = 68.2 years) and 42 poor sleepers (M age = 68.7 years). The relations among subjective ratings of sleep, level of perceived stress, and negative mood were analyzed for each group. Good and poor sleepers reported similar amounts of life stress, but the relations between life stress and sleep perceptions differed for the 2 groups. Specifically, within the group of poor sleepers, those with higher life stress had greater difficulty falling asleep and less early morning waking than did poor sleepers with lower life stress. There was no association between life stress and any sleep measures for good sleepers. These results are compatible with the notion that good and poor sleepers may have different susceptibilities to poor sleep despite experiencing similar stressful life events.

  View details for Web of Science ID A1995RV98000005

  View details for PubMedID 8527056

• LONGITUDINAL VOLUMETRIC COMPUTED TOMOGRAPHIC ANALYSIS OF REGIONAL BRAIN CHANGES IN NORMAL AGING AND ALZHEIMERS-DISEASE ARCHIVES OF NEUROLOGY Shear, P. K., SULLIVAN, E. V., Mathalon, D. H., Lim, K. O., Davis, L. F., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. 1995; 52 (4): 392-402

  Abstract

  This study used a semiautomated image analysis technique to quantify the rate and regional pattern of cerebrospinal fluid (CSF) volume changes in the computed tomographic brain examinations of healthy adults and patients with Alzheimer's disease (AD).Longitudinal, within-subject design, with statistical correction for longitudinal method error (eg, head repositioning effects).Palo Alto (Calif) Department of Veterans Affairs Medical Center.The 41 patients with AD were recruited from the Geriatric Psychiatry Research Unit and the National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 35 healthy control subjects were recruited from the local community.Cerebrospinal fluid volumes estimated from computed tomographic scans.Even after accounting for an estimate of method error (eg, head positioning effects) across computed tomographic examinations, the patients with AD showed greater annual CSF volume increases than did the control group. This CSF volume enlargement was not uniform across brain regions of interest; rather, the patients with AD showed disproportionate volume increases in the ventricular system and the sylvian fissures. Greater CSF volume changes in the patients with AD were significantly associated with greater cognitive decline on the Mini-Mental State Examination. Furthermore, younger patients with AD showed more rapid progression on computed tomographic scans than did older patients.The rate of CSF volume enlargement is region specific, with the most marked annual rate of change occurring in the ventricular system and the sylvian fissures. In addition, younger patients show more rapid progression in the ventricular and frontal sulcal brain regions of interest than do older patients.

  View details for Web of Science ID A1995QR98600014

  View details for PubMedID 7710375

• PREDICTION OF OUTCOME IN BEHAVIORALLY BASED INSOMNIA TREATMENTS JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY Bliwise, D. L., Friedman, L., NEKICH, J. C., Yesavage, J. A. 1995; 26 (1): 17-23

  Abstract

  Factors related to successful behavioral intervention for individuals with insomnia are not well understood. In this study we employed the Neuroticism, Extraversion and Openness (NEO) Personality Inventory, to predict successful treatment outcome. Two behavioral treatments for insomnia, sleep restriction therapy (SRT) and relaxation training (RT) were employed in 32 elderly insomniacs. Following two baseline weeks, subjects underwent four weeks of individual treatment. Daily telephone call-ins generated data on sleep times and sleep latency. Follow-up occurred three months after the end of treatment. Results indicated that subjects showing the greatest improvement in total sleep time with both treatments were more traditional, conventional and rigid. Improvement in sleep onset latency was unrelated to NEO Scores. SRT appeared to be more effective for increasing total sleep time in these older subjects.

  View details for Web of Science ID A1995QZ28500003

  View details for PubMedID 7642756

• IDENTIFICATION OF FAST AND SLOW DECLINERS IN ALZHEIMER-DISEASE - A DIFFERENT APPROACH Roundtable on Early-Onset Alzheimer Disease - Evidence of a Specific Subtype, at the 4th International Conference on Alzheimers Disease and Related Disorders Brooks, J. O., Yesavage, J. A. LIPPINCOTT WILLIAMS & WILKINS. 1995: S19–S25

  Abstract

  As the body of knowledge about Alzheimer disease (AD) expands, more evidence is appearing to suggest the existence of different subtypes. The delineation of subtypes is important for a variety of reasons, and there are probably several ways to identify subtypes. One crude but functionally promising distinction is between patients with early onset of AD and those with late onset. In theory, such a distinction appears to be a simple one, but critical methodologic issues are involved in this dichotomy, because a key aspect is estimating the rate of progression of the disease in different subtypes. This article discusses potential problems with various measures of deterioration and illustrates how the application of a novel technique--the trilinear model--can address many of these problems and provide additional valuable information. The trilinear model is especially well suited for use in pharmacologic studies because of the additional insight that it can provide.

  View details for Web of Science ID A1995RW67600005

  View details for PubMedID 7546595

• ESTROGEN REPLACEMENT THERAPY AND MEMORY IN OLDER WOMEN JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Robinson, D., Friedman, L., Marcus, R., Tinklenberg, J., Yesavage, J. 1994; 42 (9): 919-922

  Abstract

  To study the relationship between estrogen hormone replacement therapy and recall of proper names and words in cognitively intact older women.A case-control study using subjects matched on age and education.From a group of 278 older (age range 55 to 93 years) community-dwelling women volunteers for memory research, 72 older women taking estrogen replacement therapy were matched on age and education with a group of 72 women not taking estrogen.Dependent measures were performances on: a proper name recall test and a word recall test.Proper name recall was significantly better in those receiving estrogen (mean = 4.3; SD = 3.3) than in those not receiving estrogen (mean = 3.1; SD = 2.5), P = 0.01. There was also significantly greater variance in the name recall scores of the group taking estrogen than in the group not taking estrogen. For word recall, there was no significant difference between those subjects taking estrogen (mean = 6.4; SD 3.8) and those not taking estrogen (mean = 5.8; SD 3.7), P > 0.10.Estrogen use was associated with enhanced recall of proper names. Previous failures to find differences associated with estrogen use may reflect the memory measures used or an increased inter-individual variability of the estrogen-taking group, as was observed in the present study. Interpretation of these results should be tempered by their retrospective nature.

  View details for Web of Science ID A1994PE83200002

  View details for PubMedID 8064097

• THE EFFECTS OF INFORMATION LOAD AND SPEECH RATE ON YOUNGER AND OLDER AIRCRAFT PILOTS ABILITY TO EXECUTE SIMULATED AIR-TRAFFIC-CONTROLLER INSTRUCTIONS JOURNALS OF GERONTOLOGY Taylor, J. L., Yesavage, J. A., Morrow, D. G., DOLHERT, N., Brooks, J. O., Poon, L. W. 1994; 49 (5): P191-P200

  Abstract

  In this applied study of memory for orally presented information, 15 younger and 15 older pilots heard recorded air-traffic controller (ATC) messages in the context of six simulated flights. The ATC messages varied in length (3 vs 4 items), speech rate (235 vs 365 wpm), and type of command (course commands consisting of headings and altitudes vs radio/transponder commands consisting of radio frequencies and transponder codes). Older pilots made more execution errors on average and the age difference was greater for the radio/transponder commands, which contained more unique digits than the course commands. Although longer message lengths and faster speech rates led to higher error rates, the increases were not more marked in the older group. Backward digit span was correlated with communication performance, but the older group's lower level of accuracy was not explainable in terms of differences in digit span.

  View details for Web of Science ID A1994PE10600021

  View details for PubMedID 8056944

• ACUTE AND 8-HOUR EFFECTS OF ALCOHOL (0.08-PERCENT BAC) ON YOUNGER AND OLDER PILOTS SIMULATOR PERFORMANCE AVIATION SPACE AND ENVIRONMENTAL MEDICINE Taylor, J. L., DOLHERT, N., Morrow, D., Friedman, L., Yesavage, J. A. 1994; 65 (8): 718-725

  Abstract

  This preliminary study examined the acute and 8-hour effects of alcohol at a target peak BAC of 0.08% on pilot performance. Fourteen younger (mean age 27.6 years) and fourteen older (mean age 60.3 years) pilots flew a Frasca 141 simulator in a scenario that included ATC communications and emergencies. Plots were tested during an alcohol and placebo condition at three timepoints: predrink, acute intoxication, and 8 h postdrink. Of eight performance measures, two showed statistically significant effects related to alcohol. First, cockpit monitoring was poorer when pilots were intoxicated, with recovery at 8 h. Second, younger pilots made more communication errors under the influence and there was no significant recovery at 8 h. Older pilots made more communication errors than younger pilots, but possibly because of methodological problems, older pilots' communication performance was not significantly impaired by alcohol. These results provide direction for future research.

  View details for Web of Science ID A1994PA92100004

  View details for PubMedID 7980331

• FLIGHT SIMULATOR PERFORMANCE OF YOUNGER AND OLDER AIRCRAFT PILOTS - EFFECTS OF AGE AND ALCOHOL JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yesavage, J. A., DOLHERT, N., Taylor, J. L. 1994; 42 (6): 577-582

  Abstract

  To determine if older pilots forgot more about a learned flight task after a 10-month delay than did younger pilots and if the anticipated greater skill loss led older pilots' performance to be more disrupted by alcohol.Repeated measures comparative group design examining the effects of alcohol versus placebo in two age groups (younger and older) and at two timepoints: acute intoxication, at a Blood Alcohol Concentration (BAC) of 0.10%, and 8 hours post-drink.University medical center research laboratory.Fourteen younger (mean age = 27; SD = 4.21; range 21-34) and 13 older (mean age = 60; SD = 6.27; range 51-69) pilots, recruited from local flying clubs, with current FAA medical certificates.We examined the effects of alcohol versus placebo in the two age groups and at two times, ie, acute intoxication (target BAC 0.10%) and 8-hour post-drink. Subjects flew a Frasca 141 simulator in a flight task that they had previously learned but not practiced for several months. After completing a baseline flight, pilots were tested during either an alcohol or a placebo condition at the two timepoints. The main outcome measure was a composite measure of flight performance based upon the mean of eight component standardized scores from different aspects of the flight task.We found detrimental effects of alcohol on the main outcome measure both at the acute and 8-hour post-drink testing. There was also no significant difference between the older and younger pilots' performance of the flight task or in susceptibility to alcohol either while intoxicated or during hangover.This study replicates the findings of earlier studies that an 8-hour waiting period from "Bottle-to-Throttle" is insufficient but finds little difference according to age in recollection of a previously learned task or in susceptibility to either acute or hangover effects of alcohol.

  View details for Web of Science ID A1994NQ25100001

  View details for PubMedID 8201140

• HOW FAR VS HOW FAST IN ALZHEIMERS-DISEASE - THE QUESTION REVISITED ARCHIVES OF NEUROLOGY Kraemer, H. C., Tinklenberg, J., Yesavage, J. A. 1994; 51 (3): 275-279

  Abstract

  To expand on a recent study of 42 patients with probable Alzheimer's Disease that found that the only significant predictors of certain clinical end points were the degree of severity features at entry ("how far").A case series study of a cohort of 81 patients with Alzheimer's disease that used survival analysis methods similar those of the previous study but included a new technique for calculating rate of progression ("how fast") as well as entry characteristics ("how far").A university medical center and its affiliated Veterans Affairs Medical Center.All patients with probable and definite Alzheimer's disease studied at the Aging Clinical Research Center at Stanford University, Palo Alto, Calif, in the years 1981 and 1992 who met the following criteria: a mild to moderate level of severity of the disease (Mini-Mental State Examination score of 15 or above) at entry into the study and a minimum of three test points spaced approximately 6 months apart (to allow estimation of rate of progression). A total of 81 such patients were identified. These patients had been followed up for a mean of 4.53 +/- 2.3 years, with a range of 1.0 to 14.5 years.The outcome measure was the average rate of decline on the Mini-Mental State Examination.The results of our study replicated a previous finding that the degree of severity is a strong predictor of time course, but in addition we found that the rate of progression also appears to be a strong predictor of clinical course.There appears to be substantial heterogeneity in the rate of progression in patients with Alzheimer's disease, and, like initial degree of severity, rate of progression appears to be a strong predictor of clinical course.

  View details for Web of Science ID A1994NA08900013

  View details for PubMedID 8129639

• Spontaneous mnemonic strategies used by older and younger adults to remember proper names. Memory Brooks, J. O., Friedman, L., Gibson, J. M., Yesavage, J. A. 1993; 1 (4): 393-407

  Abstract

  Little attention has been focused on the spontaneous mnemonic strategies that people use to remember proper names. In the experiment reported here, groups of younger (< 25 years old) and older subjects (> or = 55 years old) were shown a series of 12 name-face pairs and instructed to remember them. In a subsequent test, they were shown the same faces and asked to recall the corresponding names. After the recall task, subjects completed a questionnaire about the mnemonic strategies they used. Our analyses revealed not only that the younger subjects recalled more names than did the older subjects, but also that older and younger subjects reported using certain strategies more frequently than other strategies. Moreover, regression analyses indicated that use of certain mnemonic strategies accounted for a significant proportion of recall performance beyond that accounted for by age alone. Older-old subjects (> or = 70 years old) recalled fewer names than did younger-old subjects (> or = 55 and < 70 years old), but they did not differ in the extent to which they used specific mnemonic strategies. Our results suggest that the use of spontaneous mnemonic strategies may play a role in the difference in proper name recall between younger and older adults.

  View details for PubMedID 7584279

• TYPOGRAPHY MANIPULATIONS CAN AFFECT PRIMING OF WORD STEM COMPLETION IN OLDER AND YOUNGER ADULTS PSYCHOLOGY AND AGING Gibson, J. M., Brooks, J. O., Friedman, L., Yesavage, J. A. 1993; 8 (4): 481-489

  Abstract

  The experiments reported here investigated whether changes of typography affected priming of word stem completion performance in older and younger adults. Across all experiments, the typeface in which a word appeared at presentation either did or did not match that of its 3-letter stem at test. In Experiment 1, no significant evidence of a typography effect was found when words were presented with a sentence judgment or letter judgment task. However, subsequent experiments revealed that, in both older and younger adults, only words presented with a syllable judgment task gave rise to the typography effect (Experiments 2-4). Specifically, performance was greater, when the presentation and test typeface matched than when they did not. Experiment 5, which used stem-cued recall, did not reveal a difference between syllable and letter judgment tasks. These findings highlight the complex nature of word stem completion performance.

  View details for Web of Science ID A1993MK54900002

  View details for PubMedID 8292277

• Cognitive decline in Alzheimer's disease: elaborating on the nature of the longitudinal factor structure of the Mini-Mental State Examination. International psychogeriatrics Brooks, J. O., Yesavage, J. A., Taylor, J., Friedman, L., Tanke, E. D., LUBY, V., Tinklenberg, J. 1993; 5 (2): 135-146

  Abstract

  The purpose of this paper was to use the Wechsler Adult Intelligence Scale (WAIS) to further define the nature of the underlying factors of the Mini-Mental State Examination (MMSE) as proposed by Tinklenberg et al. (1990). The MMSE was administered to 51 patients once every 6 months for at least one year; the WAIS was administered only at the beginning of the study. Stepwise regression analyses yielded these results: for the Following Commands factor, the best correlate was the Comprehension subtest; for the Language Repetition factor, the best correlate was the Picture Arrangement subtest; and for the Language Expression factor, the best correlates were the Digit Symbol and Object Assembly subtests. These relations help clarify the correlates of decline of AD patients on the MMSE.

  View details for PubMedID 8292767

• SELECTED PSYCHIATRIC-SYMPTOMS ASSOCIATED WITH RATE OF COGNITIVE DECLINE IN PATIENTS WITH ALZHEIMERS-DISEASE JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY MILLER, T. P., Tinklenberg, J. R., Brooks, J. O., FENN, H. H., Yesavage, J. A. 1993; 6 (4): 235-238

  Abstract

  We examined the relation between selected psychiatric symptoms and the average rate of decline in different areas of cognition in patients with Alzheimer's disease. Measures of decline were computed by determining patients' average rates of decline on the underlying factors of the Mini-Mental State Examination (MMSE). Patients with agitation or wandering declined more rapidly on the total MMSE score than did patients without either symptom. The Following Commands factor accounted for almost all of this decline. The findings suggest a relation between the presence of certain behavioral problems in Alzheimer's disease and decline in particular cognitive areas.

  View details for Web of Science ID A1993MA73400010

  View details for PubMedID 8251053

• THE TIME-COURSE OF ALCOHOL IMPAIRMENT OF GENERAL-AVIATION PILOT PERFORMANCE IN A FRASCA 141 SIMULATOR AVIATION SPACE AND ENVIRONMENTAL MEDICINE Morrow, D., Yesavage, J., LEIRER, V., DOLHERT, N., Taylor, J., Tinklenberg, J. 1993; 64 (8): 697-705

  Abstract

  This study examined the time-course of alcohol impairment of general aviation pilot simulator performance. We tested 14 young (mean age 25.8 years) and 14 older (mean age 37.9 years) pilots in a Frasca 141 simulator during alcohol and placebo conditions. In the alcohol condition, pilots drank alcohol and were tested after reaching 0.10% BAL, and then 2, 4, 8, 24, and 48 h after they had stopped drinking. They were tested at the same times in the placebo condition. Alcohol impaired overall performance. Alcohol impairment also depended on the order in which subjects participated in the alcohol and placebo sessions, with larger decrements for the alcohol-placebo order than for the opposite order. To examine the influence of alcohol independent of session order effects, we compared performance in the first alcohol session with performance in the first placebo session. This analysis showed that alcohol significantly reduced mean performance in the alcohol condition at 0.10% BAL and at 2 h. In addition, alcohol increased variability in performance in the alcohol session from 0.10% BAL to 8 h, suggesting that some subjects were more susceptible to alcohol than others. Older pilots tended to perform some radio communication tasks less accurately than younger pilots.

  View details for Web of Science ID A1993LP56600003

  View details for PubMedID 8368982

• DEPRESSION AS A CONFOUNDING VARIABLE IN THE ESTIMATION OF HABITUAL SLEEP TIME JOURNAL OF CLINICAL PSYCHOLOGY Bliwise, D. L., Friedman, L., Yesavage, J. A. 1993; 49 (4): 471-477

  Abstract

  Self-reported habitual sleep time is an important variable because short and long sleep times are associated with mortality. Speculation with regard to these results usually focuses on physical health, rather than psychological factors. We investigated the role of anxiety and depression in reports of habitual sleep times by examining the relative and absolute discrepancy between individuals' initial estimates of their sleep times and sleep diaries made over a 2-week period. Results indicated that depressed mood was associated not only with a tendency initially to underestimate length of sleep (relative discrepancy), but also to exaggerate reported sleep time regardless of direction (absolute discrepancy). These results imply that studies that examine relationships between reported sleep times and mortality should take mental health factors into account.

  View details for Web of Science ID A1993LT78200002

  View details for PubMedID 8408673

• THE METHODOLOGY OF STUDYING DECLINE IN ALZHEIMERS-DISEASE JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Brooks, J. O., Kraemer, H. C., Tanke, E. D., Yesavage, J. A. 1993; 41 (6): 623-628

  Abstract

  To present a new model for analyzing longitudinal data. The trilinear model is superior to the commonly used linear model that includes the flawed assumption that decline is uniform throughout the course of disease--an assumption that does not correspond to clinical observations.A longitudinal cohort sample was used to compare the linear and trilinear models. Simulated longitudinal data were generated to assess classification errors with the trilinear model.The subjects were 80 patients with Alzheimer's disease tested in a hospital out-patient clinic.The trilinear model describes Alzheimer's disease as proceeding through three periods: An initial period of stability before detectable decline, a period of decline, and a final period of stability during which there is no further detectable decline. A program for the Apple Macintosh computer is available at no charge to apply the model to data.The analyses indicated that the trilinear model provides a better reflection of decline in Alzheimer's disease than does the linear model. This advantage is present whether the periods of stability reflect a "true" lack of decline or insensitivity of a measurement instrument.The trilinear model provides not only a more accurate estimate of the average rate of change, but also (when possible) estimates of the point at which decline begins and ends. Also, more detailed comparisons of tests could be made by using the trilinear parameters. The trilinear model would benefit researchers engaged in longitudinal research of progressive disorders.

  View details for Web of Science ID A1993LF77600006

  View details for PubMedID 8505459

• Differential diagnosis between depression and dementia. American journal of medicine Yesavage, J. 1993; 94 (5A): 23S-28S

  Abstract

  The proportion of U.S. citizens > 65 years of age is growing steadily. This aging of the population is expected to bring an increase in the incidence of depression and dementia, two clinical entities common in elderly populations. Although depression and dementia have many similarities, they also have important clinical distinctions. It is important for primary-care physicians to understand these distinctions, since only approximately 20% of patients with depressive symptoms are treated by mental health practitioners.

  View details for PubMedID 8503478

• DEVELOPMENT OF APHASIA, APRAXIA, AND AGNOSIA AND DECLINE IN ALZHEIMERS-DISEASE AMERICAN JOURNAL OF PSYCHIATRY Yesavage, J. A., Brooks, J. O., Taylor, J., Tinklenberg, J. 1993; 150 (5): 742-747

  Abstract

  The purpose of this study was to compare the stage and the subtype models of disease progression in Alzheimer's disease. The authors address the issue of whether the overall rate of clinical decline is different in Alzheimer's disease patients with and without early development of aphasia, apraxia, or agnosia.The study was a case series study. Two separate cohorts of Alzheimer's disease patients were used, one from an ongoing single center study at Stanford University (N = 57) and the other from a multicenter project across the state of California (N = 70). Patients were assessed every 6 months in the Stanford study and yearly in the state study. All patients were assessed at least three times. The outcome measure was the average rate of decline on the Mini-Mental State examination.The average rates of decline on the Mini-Mental State were computed for each subject. Subjects were then divided among groups according to whether and when they exhibited aphasia, agnosia, or apraxia. The effects of the presence of aphasia, agnosia, or apraxia were assessed by comparing the average rates of decline on the Mini-Mental State.Alzheimer's disease patients who developed aphasia or apraxia declined more rapidly than those patients who did not develop either sign. These results were not attributable to differences in Mini-Mental State scores at entry into the study. The results suggest the presence of subtypes of Alzheimer's disease in which accelerated decline is associated with the early appearance of certain neurological signs.

  View details for Web of Science ID A1993LA32300010

  View details for PubMedID 8480819

• GREATER ABNORMALITIES OF BRAIN CEREBROSPINAL-FLUID VOLUMES IN YOUNGER THAN IN OLDER PATIENTS WITH ALZHEIMERS-DISEASE ARCHIVES OF NEUROLOGY SULLIVAN, E. V., Shear, P. K., Mathalon, D. H., Lim, K. O., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. 1993; 50 (4): 359-373

  Abstract

  This study used a semiautomated analysis technique to quantify differences in regional brain cerebrospinal fluid volumes observed with computed tomography between healthy adults and patients with Alzheimer's disease (AD).Cross-sectional, between-subject design, using an age-regression model.Palo Alto (Calif) Department of Veterans Affairs Medical Center.The 117 patients with probable or definite AD were recruited from the Geriatric Psychiatry Research Unit and National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 114 healthy volunteers were recruited from the local community.Cerebrospinal fluid volumes estimated from computed tomographic scans and neuropsychological test scores.The computed tomographic estimates of ventricular and sulcal cerebrospinal fluid volumes increased significantly in all sampled brain regions in normal aging and were vastly larger in AD than in normal aging. Furthermore, younger patients with AD had significantly greater cerebrospinal fluid volume enlargement than did older patients with AD compared with healthy controls of their age. When the AD group was divided on the basis of reported age at symptom onset, patients in the early-onset group (onset before age 65 years) were quantitatively more abnormal than and showed a different pattern of abnormality from the patients in the late-onset group. This onset difference was also evident in neuropsychological test performance.This cross-sectional study revealed a number of converging findings that suggested greater abnormality in the early-onset than in the late-onset group of patients with AD. The possibility remains, however, that the two onset groups represent different stages along a continuum of pathologic changes.

  View details for Web of Science ID A1993KV70200007

  View details for PubMedID 8460957

• A study of the problems older adults encounter when using a mnemonic technique. International psychogeriatrics Brooks, J. O., Friedman, L., Yesavage, J. A. 1993; 5 (1): 57-65

  Abstract

  This study explored problems older adults experience when using a mnemonic technique known as the method of loci. Older subjects received six hours of imagery, judgment, and relaxation pretraining followed by mnemonic training for either four or six hours (Regular or Extended training, respectively). At the end of training, subjects were given a list of the constituent steps of the method of loci and asked to indicate which, if any, were problematic. The factor structure of the relations among the problems varied according to the length of the training subjects received. Specifically, the factor structure of the difficulties reported by the Regular training group reflected problems with using the steps involved in the application of the method of loci, whereas for the Extended training group the factor structure reflected problems with abilities called upon in using the technique. Thus, even with Extended training, subjects may need additional pretraining to develop specific abilities necessary for the successful application of the mnemonic.

  View details for PubMedID 8499575

• Insomnia in Older Adults: Relations to Depression and Anxiety. American journal of geriatric psychiatry Friedman, L., Brooks, J. O., Bliwise, D. L., Yesavage, J. A. 1993; 1 (2): 153-159

  Abstract

  The authors examine the relations between insomnia and depression using the Beck Depression Inventory and between insomnia and anxiety using the State-Trait Anxiety Inventory and the Neuroticism Extroversion Openness-Personality Inventory (NEO) in a sample of 27 community-dwelling older patients with insomnia (mean age = 70.1 years). Sleep parameters were measured using both subjective (daily sleep logs) and objective (wrist actigraph) methods. Results varied according to the method used to measure sleep: with sleep logs, longer wake after sleep onset was related to both greater depression and anxiety (NEO), and longer time in bed was related to greater anxiety (NEO); with the actigraph, longer total sleep time was related to both greater depression and anxiety, and shorter sleep onset was related to greater depression.

  View details for DOI 10.1097/00019442-199300120-00008

  View details for PubMedID 28531030

• USE OF THE WRIST ACTIGRAPH TO STUDY INSOMNIA IN OLDER ADULTS SLEEP Brooks, J. O., Friedman, L., Bliwise, D. L., Yesavage, J. A. 1993; 16 (2): 151-155

  Abstract

  Measures derived from the wrist actigraph have been found to correlate highly with EEG measures of normal sleep. Although the actigraph has been used to study normal sleep, few studies have used the actigraph as a measure of sleep of elderly insomniacs. The present study, which used elderly insomniacs, sought to investigate the sensitivity of the actigraph to detect the effects of an insomnia treatment. The actigraph was sufficiently sensitive to detect the effect of the sleep restriction therapy used on several sleep measures. Subsidiary analyses suggested that the sleep log, although not an accurate measure of sleep, may be useful as a measure of elderly insomniacs' subjective perception of sleep. Because the actigraph can be used more easily and less expensively than the polysomnogram, the actigraph appears to be a promising measure for assessing the efficacy of treatment interventions in elderly insomniacs.

  View details for Web of Science ID A1993KN60100009

  View details for PubMedID 8446835

• INFLUENCE OF AGING AND PRACTICE ON PILOTING TASKS EXPERIMENTAL AGING RESEARCH Morrow, D., Yesavage, J., LEIRER, V., Tinklenberg, J. 1993; 19 (1): 53-70

  Abstract

  We examined how pilot age influences radio communication and routine flying tasks during simulated flight, and if practice reduces age differences in these tasks. The communication task involved reading back and executing messages with four commands (heading, altitude, communication frequency, transponder code). Routine flying tasks included takeoff, visual approach, and landing. Fifteen older (X = 38.4 years) and 16 younger (X = 26.1 years) private-license pilots flew 12 flights involving these tasks. Age differences were found in the communication task; older pilots read back and executed controller messages less accurately. However, age differences were not significant for any of the routine flying tasks except the approach. Age differences in communication performance were not reduced by practice, with older and young pilots improving at roughly the same rate across flights. These results are consistent with previous research showing age-related declines in working memory capacity. Capacity declines would produce greater age differences on communication than on routine flying tasks because the communication tasks imposed a greater load on working memory.

  View details for Web of Science ID A1993KN48000005

  View details for PubMedID 8444267

• SUBTYPES IN ALZHEIMERS-DISEASE AND THE IMPACT OF EXCESS DISABILITY - RECENT FINDINGS INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY FENN, H., LUBY, V., Yesavage, J. A. 1993; 8 (1): 67-73

  View details for Web of Science ID A1993KH52500010

• MARIJUANA CARRY-OVER EFFECTS ON PSYCHOMOTOR PERFORMANCE - A CHRONICLE OF RESEARCH 2nd International Colloquium on the Physiopathology of Cannabis and the Detection of Illicit Drugs Leirer, V. O., Yesavage, J. A., Morrow, D. G. CRC PRESS INC. 1993: 47-?

  View details for Web of Science ID A1993BA36H00003

• SUNDOWNING AND RATE OF DECLINE IN MENTAL FUNCTION IN ALZHEIMERS-DISEASE DEMENTIA Bliwise, D. L., Yesavage, J. A., Tinklenberg, J. R. 1992; 3 (5-6): 335-341

  View details for Web of Science ID A1992KC01100010

• THE RELATIONS AMONG CAREGIVER STRESS, SUNDOWNING SYMPTOMS, AND COGNITIVE DECLINE IN ALZHEIMERS-DISEASE JOURNAL OF THE AMERICAN GERIATRICS SOCIETY GALLAGHERTHOMPSON, D., Brooks, J. O., Bliwise, D., Leader, J., Yesavage, J. A. 1992; 40 (8): 807-810

  Abstract

  To investigate the relations among the initial perceived stress of Alzheimer patients' caregivers, the rate of change of perceived stress, patients' sundowning behaviors, and patients' rate of cognitive decline.A longitudinal cohort study in which Alzheimer patients and their caregivers were assessed at 6-month intervals.Hospital out-patient clinic. Patients and caregivers lived at home.Subjects were 35 patients (50-79 years) with Alzheimer's disease and their primary caregivers (24 males and 11 females); all caregivers were spouses.At time of entry into the study, caregivers indicated which of seven behaviors indicative of sundowning were exhibited by the patient. Patients were evaluated successively using the Mini-Mental State Examination, whereas caregivers completed the Perceived Stress Scale, provided an index of social support utilization, and completed the Beck Depression Inventory.Caregivers' initial perceived stress and the rate of change of perceived stress, patients' sundowning behavior, and rate of cognitive decline.The pattern of correlations indicated that both rate of cognitive decline and initial sundowning behavior were significantly correlated with initial perceived caregiver stress. The average rate of increase of caregivers' perceived stress was positively correlated with the initial incidence of sundowning behaviors, even when controlling for the effects of caregiver depression and social support utilization.Sundowning behavior of Alzheimer patients is associated with an increased rate of change of caregivers' perceived stress. This association may be specific to sundowning behavior because there was no relation between the rate of change of perceived stress and morning agitation. The findings suggest that future caregiver intervention programs could profitably focus on sundowning behavior rather than general agitation.

  View details for Web of Science ID A1992JH34400009

  View details for PubMedID 1634724

• TIMING OF SLEEP AND WAKEFULNESS IN ALZHEIMERS-DISEASE PATIENTS RESIDING AT HOME BIOLOGICAL PSYCHIATRY Bliwise, D. L., Tinklenberg, J. R., Yesavage, J. A. 1992; 31 (11): 1163-1165

  View details for Web of Science ID A1992JK71800011

  View details for PubMedID 1525280

• DEPRESSION IN THE ELDERLY - HOW TO RECOGNIZE MASKED SYMPTOMS AND CHOOSE APPROPRIATE THERAPY POSTGRADUATE MEDICINE Yesavage, J. A. 1992; 91 (1): 255-?

  Abstract

  Depression in the elderly is one of the most serious undiagnosed health problems in the United States. All physicians who care for elderly patients need to become aware of the signs of masked depression and treat it vigorously. Dr Yesavage explains how to differentiate depression from dementia, describes useful diagnostic screening tests, and offers recommendations for pharmacologic treatment of geriatric depression.

  View details for Web of Science ID A1992HA24700024

  View details for PubMedID 1728777

• EFFECTS OF PHOSPHATIDYLSERINE IN AGE-ASSOCIATED MEMORY IMPAIRMENT AND ALZHEIMERS-DISEASE 2ND SUNCOAST WORKSHOP ON THE NEUROBIOLOGY OF AGING Crook, T. H., Tinklenberg, J., Yesavage, J., Petrie, W., Wells, C., Nunzi, M. G., MASSARI, D. C. PLENUM PRESS DIV PLENUM PUBLISHING CORP. 1992: 207–224

  View details for Web of Science ID A1992BW50H00017

• NUTRITIONAL INTAKE IN PATIENTS WITH SENILE DEMENTIA OF THE ALZHEIMER TYPE ALZHEIMER DISEASE & ASSOCIATED DISORDERS Winograd, C. H., Jacobson, D. H., Butterfield, G. E., CRAGEN, E., EDLER, L. A., Taylor, B. S., Yesavage, J. A. 1991; 5 (3): 173-180

  Abstract

  The dietary intake of 29 healthy controls was compared with that of 35 community-dwelling patients with probable or definite senile dementia of the Alzheimer type (SDAT), based on NINCDS-ADRDA criteria. The control subject or the caregiver of the SDAT patient completed a 3-day estimated-dietary-intake record. Foods offered to patients were chosen, for the most part, by caregivers, but SDAT patients were allowed to eat ad libitum from those choices, and food consumed was recorded. Dietary intake was evaluated against the 1989 Recommended Dietary Allowances (RDA). Dietary intakes did not differ significantly between control and SDAT patients for any of the 32 nutrients analyzed. The controls and SDAT patients met the RDA guidelines for intake of total energy, protein, and micronutrients, with the exception of female SDAT patients, who did not consume a minimum of two thirds of the RDA for vitamin D. All biochemical indices of nutritional status were within normal limits for the SDAT patients. In addition, cognitive function did not correlate with intake of any nutrient studied. We conclude that moderately impaired, community-dwelling patients with SDAT do not differ from healthy controls in nutritional status or nutrient intake. Neither general nor nutrient-specific malnutrition was present in this population. Based on this cross-sectional study, malnutrition does not appear to be a major contributor to the pathogenesis of Alzheimer disease. However, this investigation examined only a single point in time, when patients were being fed by caregivers, so that the role of malnutrition at the beginning of the disease was not addressed.

  View details for Web of Science ID A1991GU43100003

  View details for PubMedID 1772637

• BLOOD-GLUCOSE AND INSULIN-RESPONSE IN PATIENTS WITH SENILE DEMENTIA OF THE ALZHEIMERS TYPE BIOLOGICAL PSYCHIATRY Winograd, C. H., Jacobson, D. H., Minkoff, J. R., Peabody, C. A., Taylor, B. S., WIDROW, L., Yesavage, J. A. 1991; 30 (5): 507-511

  View details for Web of Science ID A1991GE87200011

  View details for PubMedID 1932397

• EFFECTS OF PHOSPHATIDYLSERINE IN AGE-ASSOCIATED MEMORY IMPAIRMENT NEUROLOGY Crook, T. H., Tinklenberg, J., Yesavage, J., Petrie, W., Nunzi, M. G., MASSARI, D. C. 1991; 41 (5): 644-649

  Abstract

  We treated 149 patients meeting criteria for age-associated memory impairment (AAMI) for 12 weeks with a formulation of phosphatidylserine (100 mg BC-PS tid) or placebo. Patients treated with the drug improved relative to those treated with placebo on performance tests related to learning and memory tasks of daily life. Analysis of clinical subgroups suggested that persons within the sample who performed at a relatively low level prior to treatment were most likely to respond to BC-PS. Within this subgroup, there was improvement on both computerized and standard neuropsychological performance tests, and also on clinical global ratings of improvement. The results suggest that the compound may be a promising candidate for treating memory loss in later life.

  View details for Web of Science ID A1991FK92800006

  View details for PubMedID 2027477

• Proposed factor structure of the Geriatric Depression Scale. International psychogeriatrics Sheikh, J. I., Yesavage, J. A., Brooks, J. O., Friedman, L., GRATZINGER, P., Hill, R. D., Zadeik, A., Crook, T. 1991; 3 (1): 23-28

  Abstract

  The Geriatric Depression Scale (GDS) is commonly used to measure depression in the elderly. However, there have been no reports of the underlying structure of the GDS. To this end, the GDS was administered to 326 community-dwelling elderly subjects, and the data were subjected to a factor analysis. A five-factor solution was selected and, after a varimax rotation, the factors that emerged could be described as: (1) sad mood, (2) lack of energy, (3) positive mood, (4) agitation, and (5) social withdrawal. This solution accounted for 42.9% of the variance. Knowledge of the factor structure should aid both clinicians and researchers in the interpretation of responses on the GDS.

  View details for PubMedID 1863703

• MARIJUANA CARRY-OVER EFFECTS ON AIRCRAFT PILOT PERFORMANCE AVIATION SPACE AND ENVIRONMENTAL MEDICINE Leirer, V. O., Yesavage, J. A., Morrow, D. G. 1991; 62 (3): 221-227

  Abstract

  This study finds evidence for 24-h carry-over effects of a moderate social dose of marijuana on a piloting task. In separate sessions, nine currently active pilots smoked one cigarette containing 20 mg of delta 9 THC and one Placebo cigarette. Using an aircraft simulator, pilots flew just before smoking, and 0.25, 4, 8, 24, and 48 h after smoking. Marijuana impaired performance at 0.25, 4, 8, and 24 h after smoking. While seven of the nine pilots showed some degree of impairment at 24 h after smoking, only one reported any awareness of the drug's effects. The results support our preliminary study and suggest that very complex human/machine performance can be impaired as long as 24 h after smoking a moderate social dose of marijuana, and that the user may be unaware of the drug's influence.

  View details for Web of Science ID A1991EZ17100005

  View details for PubMedID 1849400

• ALCOHOL, AGE, AND PILOTING - JUDGMENT, MOOD, AND ACTUAL PERFORMANCE INTERNATIONAL JOURNAL OF THE ADDICTIONS Morrow, D., LEIRER, V., Yesavage, J., Tinklenberg, J. 1991; 26 (6): 669-683

  Abstract

  We have previously described acute and carry-over effects of alcohol on young and older pilots' performance. In the present paper we report the effects of alcohol and age on self-assessment of performance and mood in the same study. Young and older pilots flew in a simulator during an alcohol and placebo condition. In the alcohol condition, they flew after reaching .04 g/dL (.04%) BAL, after .10% BAL, and then 2, 4, 8, 24, and 48 h after .10% BAL (they flew at the same times in the placebo condition). They rated confidence in ability to fly, mood, alertness, and intoxication before each flight, and perceived workload and performance after each flight. As reported in Morrow et al., alcohol had both acute and carry-over effects for 8 h on actual flight performance, with greater acute impairment for older pilots. The present study reports that these older pilots tended to be more aware than the young pilots of acute and carry-over alcohol impairment out to 4 h. By 8 h, however, all pilots were unaware of impairment. Alcohol also had a biphasic effect on mood, which increased on the ascending limb and decreased on the descending limb of the BAL curve.

  View details for Web of Science ID A1991GF43400004

  View details for PubMedID 1757171

• Physician staffing and patient violence. The Bulletin of the American Academy of Psychiatry and the Law Carmel, H., Tanke, E. D., Yesavage, J. A. 1991; 19 (1): 49-51

  Abstract

  We found an inverse relation between physical aggression by patients and physician staffing--when more physicians were available, physical aggression decreased. Episodes of nonphysical aggression increased with higher levels of psychiatrist staffing, but were not related to general physician staffing.

  View details for PubMedID 2039846

• EFFECTS OF PHOSPHATIDYLSERINE IN AGE-ASSOCIATED MEMORY IMPAIRMENT 5TH WORLD CONGRESS OF BIOLOGICAL PSYCHIATRY Crook, T., Tinklenberg, J., Yesavage, J., Petrie, W., Nunzi, M. G., MASSARI, D. C. ELSEVIER SCIENCE PUBL B V. 1991: 112–114

  View details for Web of Science ID A1991BU83L00032

• A PRELIMINARY-STUDY COMPARING SLEEP RESTRICTION AND RELAXATION TREATMENTS FOR INSOMNIA IN OLDER ADULTS JOURNALS OF GERONTOLOGY Friedman, L., Bliwise, D. L., Yesavage, J. A., SALOM, S. R. 1991; 46 (1): P1-P8

  Abstract

  This study compared Sleep Restriction Therapy (SRT) and Relaxation Therapy (RLT) as treatments for insomnia in a sample of community-residing elderly (mean age, 69.7 years). SRT subjects (n = 10) and RLT subjects (n = 12) reported information about their sleep twice daily to a telephone recording machine for 2 weeks of baseline, 4 weeks of treatment, and 2 weeks at 3-month follow-up. Results showed sleep latency and waking after sleep onset were significantly reduced for both treatment groups under active treatment. Predictable reductions in time in bed and improved sleep efficiency reported during active treatment by SRT subjects were still apparent at 3-month follow-up; no corresponding changes were found for RLT. In both groups, increased total sleep time was reported at follow-up; the improvement for SRT subjects was approximately twice that seen in RLT. These findings, at this early stage in the development of behavioral treatments for insomnia in older adults, encourage further study.

  View details for Web of Science ID A1991FJ10900006

  View details for PubMedID 1986039

• Cognitive decline in patients with Alzheimer disease: differences in patients with and without extrapyramidal signs. Alzheimer disease & associated disorders MILLER, T. P., Tinklenberg, J. R., Brooks, J. O., Yesavage, J. A. 1991; 5 (4): 251-256

  Abstract

  We investigated the relationship between extrapyramidal signs (EPSs) in patients diagnosed with Alzheimer disease (AD) and the average rate of decline in different areas of cognition. The presence of tremors, cogwheel rigidity, or bradykinesia were scored as EPS using the California State Department of Health Services AD Diagnostic and Treatment Center Form. Measures of decline were computed by determining patients' average rates of decline on the Mini-Mental State Examination (MMSE). Of the 81 patients, 24 were determined to have EPS not related to medications. Overall, patients with EPS deteriorated 67% faster on MMSE (4.5 points per year) than did patients with no evidence of EPS (2.7 points per year). Our findings indicate that the clinical presence of EPS is a poor overall prognostic sign in patients with a clinical diagnosis of AD.

  View details for PubMedID 1781967

• LONGITUDINAL CHANGES IN REM-SLEEP IN ALZHEIMERS-DISEASE 5TH WORLD CONGRESS OF BIOLOGICAL PSYCHIATRY Guilleminault, C., Bliwise, D., Yesavage, J. A. ELSEVIER SCIENCE PUBL B V. 1991: 849–850

  View details for Web of Science ID A1991BU87G00253

• A QUANTITATIVE-ANALYSIS OF CT AND COGNITIVE MEASURES IN NORMAL AGING AND ALZHEIMERS-DISEASE PSYCHIATRY RESEARCH-NEUROIMAGING Pfefferbaum, A., SULLIVAN, E. V., Jernigan, T. L., Zipursky, R. B., Rosenbloom, M. J., Yesavage, J. A., Tinklenberg, J. R. 1990; 35 (2): 115-136

  Abstract

  Patients with presumptive Alzheimer's disease (AD) and healthy community volunteers received computed tomographic (CT) brain scans and cognitive tests. The CT scans were quantitatively analyzed with a semiautomated thresholding technique to derive volumetric measures of cerebrospinal fluid (CSF)-to-tissue ratios in six regions of interest (ROIs): lateral ventricles; vertex sulci, frontal sulci, Sylvian fissures, parieto-occipital sulci, and third ventricle. Regression analysis was performed on CT data from 85 older volunteers (ages 51-82) to generate age norms for each ROI. Within this group, tissue loss, as measured by the % CSF in each ROI, was highly correlated with age, although each ROI showed different rates of change over age. For all ROIs, the AD group had significantly more tissue loss than expected in normal aging. In addition, AD patients with a presenescent onset (before age 65) tended to have greater vertex sulcal and frontal sulcal tissue reduction than AD patients with a senescent onset (age 65 or after). When regional tissue reduction, corrected for age, was correlated with cognitive test scores, two sets of double dissociations emerged within the AD group: large CT z scores (i.e., decreased tissue and increased CSF) of frontal sulci, but not of the third ventricle, correlated with low Comprehension and Boston Naming Test scores, whereas large CT z scores of the third ventricle, but not of the frontal sulci, correlated with low scores on Digit Symbol and Picture Arrangement. These results suggest that heterogeneity of structural and functional integrity exists among patients with AD.

  View details for Web of Science ID A1990EU28600003

  View details for PubMedID 2100804

• COGNITIVE INTERVENTIONS TO IMPROVE FACE-NAME RECALL - THE ROLE OF PERSONALITY-TRAIT DIFFERENCES DEVELOPMENTAL PSYCHOLOGY GRATZINGER, P., Sheikh, J. I., Friedman, L., Yesavage, J. A. 1990; 26 (6): 889-893

  View details for Web of Science ID A1990EJ88100003

• Factor analysis and preliminary validation of the mini-mental state examination from a longitudinal perspective. International psychogeriatrics Tinklenberg, J., Brooks, J. O., Tanke, E. D., Khalid, K., POULSEN, S. L., Kraemer, H. C., Gallagher, D., Thornton, J. E., Yesavage, J. A. 1990; 2 (2): 123-134

  Abstract

  The Mini-Mental State Examination (MMSE) is a commonly used instrument for assessing mental impairment. Previous proposals for its underlying structure have focused on scores obtained from a single administration of the test. Because the MMSE is widely used in longitudinal studies, we examined the pattern of relations among the rates of chance of the items. Data were obtained from 63 subjects for 1.5 years or more. The relations among the rates of change of the MMSE items were described by a five-factor solution that accounted for 75% of the variance and comprised factors pertaining to orientation and concentration, obeying commands, learning and repetition, language, and recall. This was in contrast to the structure of the scores obtained from a single administration of the MMSE, which was best described by a two-factor solution. In order to provide a clinical validation, factor scores derived from the MMSE factors were used to predict scores on the Memory and Behavior Problems Checklist and the Brief Cognitive Rating Scale.

  View details for PubMedID 2101301

• ASPECTS OF CONSENSUS IN CLINICAL-PREDICTIONS OF IMMINENT VIOLENCE JOURNAL OF CLINICAL PSYCHOLOGY Werner, P. D., Rose, T. L., Yesavage, J. A. 1990; 46 (4): 534-538

  Abstract

  This research studied individual differences among psychiatric patients in the extent to which clinical workers agree about the likelihood that the patients will act violently. Predictions of imminent violence proneness for 40 male inpatients made by 35 experienced clinical practitioners were analyzed. As hypothesized, subgroups of patients who elicited high interjudge agreement were found, and admission profiles of these patients were presented. Clinical workers' predictive accuracy was found to be greater when they rated patients who elicited high consensus than for unselected patients or for those who elicited low consensus.

  View details for Web of Science ID A1990DT74300022

  View details for PubMedID 2212059

• LEARNING MNEMONICS - ROLES OF AGING AND SUBTLE COGNITIVE IMPAIRMENT PSYCHOLOGY AND AGING Yesavage, J. A., Sheikh, J. I., Friedman, L., Tanke, E. 1990; 5 (1): 133-137

  Abstract

  Previously validated methods of memory training were used in conjunction with the Folstein Mini-Mental State Examination (MMSE) to explore the relationship between complexity of learned mnemonic, aging, and subtle cognitive impairment. Subjects were 218 community-dwelling elderly. Treatment included imagery mnemonics for remembering names and faces and lists. There was a significant interaction among age, type of learning task (face-name vs. list), and improvement when controlling for MMSE score. There was also a significant interaction among MMSE score, type of learning task, and improvement when controlling for age. Scores on the more complex list-learning mnemonic were more affected by age and MMSE scores than were scores on the face-name mnemonic. Implications of the findings for cognitive training of the old old and the impaired are discussed.

  View details for Web of Science ID A1990CR69600016

  View details for PubMedID 2317292

• THE INFLUENCE OF ALCOHOL AND AGING ON RADIO-COMMUNICATION DURING FLIGHT AVIATION SPACE AND ENVIRONMENTAL MEDICINE Morrow, D., LEIRER, V., Yesavage, J. 1990; 61 (1): 12-20

  Abstract

  This study finds that alcohol and pilot age impair radio communication during simulated flight. Young (mean age 25 years) and older (mean age 42 years) pilots flew in a light aircraft simulator during alcohol and placebo conditions. In the alcohol condition, pilots drank alcohol and flew after reaching 0.04% BAC, after reaching 0.10% BAC, and then 2, 4, 8, 24, and 48 h after they stopped drinking at 0.10% BAC. They flew at the same times in the placebo condition. Alcohol and age impaired communication-based and overall flying performance during and immediately after drinking. Most important, alcohol and age cumulatively impaired performance, since older pilots were more impaired by alcohol. Notably, performance was as impaired 2 h after reaching 0.10% BAC as it was at 0.10% BAC. Moreover, overall performance was impaired for 8 h after reaching 0.10% BAC.

  View details for Web of Science ID A1990CF02700003

  View details for PubMedID 2302121

• MARIJUANA, AGING, AND TASK-DIFFICULTY EFFECTS ON PILOT PERFORMANCE AVIATION SPACE AND ENVIRONMENTAL MEDICINE LEIRER, O., Yesavage, J. A., Morrow, D. G. 1989; 60 (12): 1145-1152

  Abstract

  This study provides evidence that diverse factors can cumulatively contribute to human/machine performance decrements. In separate sessions, young and old pilots smoked one of three cigarettes containing either 0 mg, 10 mg, or 20 mg of the active ingredient, delta 9 THC. They flew a calm and a turbulent flight in a light aircraft simulator at 1, 4, 8, 24, and 48 hour (h) delay after smoking. Effects were found at 1 and 4 h after smoking in the turbulent flight conditions when 20 mg cigarettes were smoked. Drug dose level, age, weather conditions (i.e., task difficulty), and delay period all affected pilot performance. Most important, these variables produced cumulative performance decrements.

  View details for Web of Science ID A1989CC44500001

  View details for PubMedID 2604668

• SOCIAL-WORKERS DECISION-MAKING ABOUT THE VIOLENT CLIENT SOCIAL WORK RESEARCH & ABSTRACTS Werner, P. D., Rose, T. L., Murdach, A. D., Yesavage, J. A. 1989; 25 (3): 17-20

  View details for Web of Science ID A1989AT40600003

• SLEEP-APNEA IN ALZHEIMERS-DISEASE NEUROBIOLOGY OF AGING Bliwise, D. L., Yesavage, J. A., Tinklenberg, J. R., Dement, W. C. 1989; 10 (4): 343-346

  Abstract

  Mental deterioration accompanying sleep apnea has been noted frequently. Because sleep apnea increases with age, such deficits raise the possibility that dementia in the elderly could be related to sleep apnea. In this study we investigated this possibility cross-sectionally by comparing respiration during sleep in 28 patients with Alzheimer's disease (AD) and 25 nondemented controls. We hypothesized that higher levels of sleep apnea would be present in AD patients. Our results indicated no significant differences between AD patients and controls but those few AD patients who desaturated during sleep experienced morning confusion. The findings imply that AD and sleep apnea are two separate conditions which may still interact in the aged.

  View details for Web of Science ID A1989AK79000008

  View details for PubMedID 2812195

• REM LATENCY IN ALZHEIMERS-DISEASE BIOLOGICAL PSYCHIATRY Bliwise, D. L., Tinklenberg, J., Yesavage, J. A., Davies, H., PURSLEY, A. M., PETTA, D. E., WIDROW, L., Guilleminault, C., Zarcone, V. P., Dement, W. C. 1989; 25 (3): 320-328

  Abstract

  Latency to the first episode of rapid eye movement sleep (REML) has been proposed as a potential biomarker for Alzheimer's disease (AD). In this study, we compared REML values from 28 AD patients and 28 age- and sex-matched controls. We employed multiple definitions of REML and multiple cutoffs to classify patients and controls. Results indicated that the best REML definition and optimal cutoff criterion resulted in only 65% correct classifications. We discuss the longer REML in AD patients relative to controls in terms of both overall sleep disturbance and selective deterioration of the REM-cholinergic system. As REML may be relatively short in other forms of psychopathology (e.g., affective disorders), REML may still hold promise in the differential diagnosis of dementia and pseudodementia.

  View details for Web of Science ID A1989R741100008

  View details for PubMedID 2914155

• MENTAL STATUS AS A PREDICTOR OF RESPONSE TO MEMORY TRAINING IN OLDER ADULTS EDUCATIONAL GERONTOLOGY Hill, R. D., Yesavage, J. A., Sheikh, J., Friedman, L. 1989; 15 (6): 633-639

  View details for Web of Science ID A1989CG05000007

• USE OF FLIGHT SIMULATORS TO INVESTIGATE THE EFFECTS OF ALCOHOL AND OTHER DRUGS ON PILOT PERFORMANCE .2. 5TH INTERNATIONAL SYMP ON AVIATION PSYCHOLOGY Morrow, D., Yesavage, J., LEIRER, V. OHIO STATE UNIV DEPT AVIATION. 1989: 203–208

  View details for Web of Science ID A1989BS50S00029

• TECHNIQUES FOR COGNITIVE TRAINING OF MEMORY IN AGE-ASSOCIATED MEMORY IMPAIRMENT ARCHIVES OF GERONTOLOGY AND GERIATRICS Yesavage, J. A. 1989: 185-190

  View details for Web of Science ID A1989U568100015

  View details for PubMedID 2757731

• THE EFFECTS OF AGE ON RECALL OF INFORMATION FROM A SIMULATED TELEVISION-NEWS BROADCAST EDUCATIONAL GERONTOLOGY Hill, R. D., Crook, T. H., ZADEK, A., Sheikh, J., Yesavage, J. 1989; 15 (6): 607-613

  View details for Web of Science ID A1989CG05000005

• ASSOCIATION STUDY BETWEEN ALZHEIMERS-DISEASE AND RESTRICTION FRAGMENT LENGTH POLYMORPHISMS AT THE HUMAN AMYLOID BETA PROTEIN GENE LOCUS MOLECULAR BIOLOGY & MEDICINE Taylor, J. E., Tinklenberg, J. R., Eng, L. F., Yesavage, J. A., Vinogradov, S., Davies, H. G., GONZALEZDEWHITT, P. A., Frossard, P. M. 1988; 5 (3): 167-172

  Abstract

  Alzheimer's disease, an autosomal dominant disorder, is characterized by the presence of neurofibrillary tangles and senile extracellular plaques in the brain of affected individuals. An amyloid beta protein has been isolated from the core of these plaques, and the gene encoding this protein has been mapped to region q11.2 to q22.2 of chromosome 21. Independent linkage studies have shown that the locus responsible for familial Alzheimer's disease also maps to the long arm of chromosome 21. It is thus very tempting to speculate that a defect (or defects) of the amyloid beta protein gene is the cause of Alzheimer's disease. For this reason, we have done association studies between Alzheimer's disease and restriction fragment length polymorphisms of the amyloid beta protein gene locus. We report a study of six restriction fragment length polymorphisms at the human amyloid beta protein gene locus. Several haplotypes constitute very informative marker systems for this region of chromosome 21. One of the six polymorphisms, a 6.6/7.3 kb (kb = 10(3) base-pairs) EcoRI restriction fragment length polymorphism, is loosely associated with the presence of Alzheimer's disease in a population of 34 subjects.

  View details for Web of Science ID A1988T295100004

  View details for PubMedID 2907602

• HUMAN AMYLOID BETA PROTEIN GENE LOCUS - HAEIII RFLP NUCLEIC ACIDS RESEARCH Taylor, J. E., GONZALEZDEWHITT, P. A., Fuller, F., Cordell, B., Tinklenberg, J. R., Davies, H. D., Eng, L. F., Yesavage, J. A., Frossard, P. M. 1988; 16 (14): 7217-7217

  View details for Web of Science ID A1988P435200072

• Human amyloid beta protein gene locus: HaeIII RFLP. Nucleic acids research Taylor, J. E., Gonzalez-DeWhitt, P. A., Fuller, F., Cordell, B., Tinklenberg, J. R., Davies, H. D., Eng, L. F., Yesavage, J. A., Frossard, P. M. 1988; 16 (14B): 7217-?

  View details for PubMedID 2900504

  View details for PubMedCentralID PMC338397

• ECOT14I-RFLP FOUND AT THE HUMAN AMYLOID BETA-PROTEIN GENE LOCUS NUCLEIC ACIDS RESEARCH Taylor, J. E., Cordell, B., Fuller, F., GONZALEZDEWHITT, P. A., Tinklenberg, J. R., Davies, H. D., Eng, L. F., Yesavage, J. A., Frossard, P. M. 1988; 16 (13): 6259-6259

  View details for Web of Science ID A1988P228300071

  View details for PubMedID 2899881

  View details for PubMedCentralID PMC336894

• Nonpharmacologic treatment of age-associated memory impairment. Comprehensive therapy Yesavage, J. A., Sheikh, J. I. 1988; 14 (6): 44-46

  View details for PubMedID 3046835

• RESPONSE TO MEMORY TRAINING AND INDIVIDUAL-DIFFERENCES IN VERBAL INTELLIGENCE AND STATE ANXIETY AMERICAN JOURNAL OF PSYCHIATRY Yesavage, J. A., Sheikh, J., Tanke, E. D., Hill, R. 1988; 145 (5): 636-639

  Abstract

  Prior studies have documented the effectiveness of several types of memory training for the elderly with normal age-related memory losses. Despite these positive results, there is substantial variability of individual response to treatment. The authors describe attributes of individuals most likely to benefit from two types of memory training. They found that for 40 elderly volunteers performance on the WAIS vocabulary subscale correlated with response to a treatment combining mnemonics and verbal elaboration techniques and scores on the Spielberger State-Trait Anxiety Inventory correlated with response to a treatment combining mnemonics and relaxation techniques.

  View details for Web of Science ID A1988N140600018

  View details for PubMedID 3282452

• VALIDATION OF THE GERIATRIC PSYCHIATRY KNOWLEDGE TEST HOSPITAL AND COMMUNITY PSYCHIATRY Sheikh, J. I., Yesavage, J. A., GULEVICH, G. 1988; 39 (4): 369-?

  View details for Web of Science ID A1988M776800003

  View details for PubMedID 3371903

• RATES OF CHANGE OF COMMON MEASURES OF IMPAIRMENT IN SENILE DEMENTIA OF THE ALZHEIMERS TYPE PSYCHOPHARMACOLOGY BULLETIN Yesavage, J. A., POULSEN, S. L., Sheikh, J., Tanke, E. 1988; 24 (4): 531-534

  View details for Web of Science ID A1988T349900006

  View details for PubMedID 3074314

• PRETRAINING ENHANCES MNEMONIC TRAINING IN ELDERLY ADULTS EXPERIMENTAL AGING RESEARCH Hill, R. D., Sheikh, J. I., Yesavage, J. A. 1988; 14 (4): 207-211

  Abstract

  One hundred twenty-eight elderly adults were recruited to assess the effects of affective judgment, imagery, and relaxation pretraining on mnemonic training. Participants were assigned to one of the following conditions: (1) visual imagery and affective judgment pretraining plus mnemonic training, (2) visual imagery pretraining only plus mnemonic training, (3) relaxation pretraining plus mnemonic training, (4) nonspecific pretraining plus mnemonic training, (5) nonspecific pretraining only, and (6) wait list. Subjects were tested at three times: prior to training (Time 1), following pretraining (Time 2), and at the conclusion of mnemonic training (Time 3). Although those receiving active pretraining plus mnemonics did not differ from one another at Time 3, they recalled more than those with no active pretraining. The results suggest that for mnemonics to be effective they should be coupled with active pretraining techniques.

  View details for Web of Science ID A1988AA96600006

  View details for PubMedID 3075181

• ASSOCIATIONS BETWEEN ALZHEIMERS-DISEASE AND RFLPS AT THE HUMAN AMYLOID BETA-PROTEIN GENE LOCUS PSYCHOPHARMACOLOGY BULLETIN Tinklenberg, J. R., Taylor, J. E., Eng, L. F., Yesavage, J. A., Vinogradov, S., Gonzalez, P. A., Davies, H. D., Frossard, P. M. 1988; 24 (3): 489-491

  View details for Web of Science ID A1988T061000041

  View details for PubMedID 2908678

• TARDIVE-DYSKINESIA AND STEADY-STATE SERUM LEVELS OF THIOTHIXENE ARCHIVES OF GENERAL PSYCHIATRY Yesavage, J. A., Tanke, E. D., Sheikh, J. I. 1987; 44 (10): 913-915

  Abstract

  The purpose of this investigation was to determine the relationship between serum levels of the neuroleptic agent thiothixene and tardive dyskinesia in schizophrenics of a wide age range. Forty-one male schizophrenic subjects, 21 with tardive dyskinesia and 20 without, were given a fixed dosage of thiothixene hydrochloride (10 mg orally four times daily) after a drug-free period of one week. Higher steady-state serum levels of thiothixene (obtained after five days of a fixed-dosage schedule) were associated with greater degrees of tardive dyskinesia. This relationship was independent of the relationship between tardive dyskinesia and age.

  View details for Web of Science ID A1987K304500011

  View details for PubMedID 2889439

• IMAGERY MNEMONIC TRAINING IN A PATIENT WITH PRIMARY DEGENERATIVE DEMENTIA PSYCHOLOGY AND AGING Hill, R. D., Evankovich, K. D., Sheikh, J. I., Yesavage, J. A. 1987; 2 (2): 204-205

  Abstract

  A visual-imagery mnemonic was used as a memory training aid for a 66-year-old patient with primary degenerative dementia. Length of retention time was used as the primary outcome measure. The application of the mnemonic procedure extended the length of retention time for name-face recall from baseline. Performance gains were sustained at one month.

  View details for Web of Science ID A1987H556800013

  View details for PubMedID 3268209

• THE EFFECT OF MNEMONIC TRAINING ON PERCEIVED RECALL CONFIDENCE IN THE ELDERLY EXPERIMENTAL AGING RESEARCH Hill, R. D., Sheikh, J. I., Yesavage, J. 1987; 13 (4): 185-188

  Abstract

  This study examined the effects of memory training on the relationship between perceived recall confidence and recall performance. The sample consisted of 76 elderly, community dwelling volunteers. Fifty-nine individuals received eight hours of memory training; the remaining 17 were wait-list controls. Participants were tested at pre- and post-intervention, and rated their confidence for recall of name-face pairs prior to each testing. The results showed a significant improvement in name-face recall at post test, favoring the group receiving mnemonic training. There was a significant association found between confidence ratings and recall performance at post-test. A closer examination of standardized regression residuals (confidence ratings and number of name-face pairs recalled) revealed that with mnemonic training, there was an improvement in the relationship between perceived confidence and recall performance following mnemonic training. The results suggest that the ability to assess changes in recall capacity and to judge future memory performance is enhanced by exposure to mnemonic training.

  View details for Web of Science ID A1987P170500003

  View details for PubMedID 3505872

• HANGOVER EFFECTS ON AIRCRAFT PILOTS 14 HOURS AFTER ALCOHOL INGESTION - A PRELIMINARY-REPORT AMERICAN JOURNAL OF PSYCHIATRY Yesavage, J. A., Leirer, V. O. 1986; 143 (12): 1546-1550

  Abstract

  Using a repeated measures counterbalanced design, the authors had 10 Navy P3-C Orion pilots fly two carefully designed simulated flights under control (no hangover) and hangover conditions. For the control condition, pilots drank no alcohol within 48 hours before the simulated flight. For the hangover condition, they flew 14 hours after drinking enough ethanol mixed with diet soft drinks to attain a blood alcohol concentration of 100 mg/dl. Pilot performance was worse in the hangover condition on virtually all measures but significantly worse on three of six variance measures and one of six performance measures. The results indicate that caution should be exercised when piloting an aircraft 14 hours or less after ingesting similar quantities of alcohol.

  View details for Web of Science ID A1986F055000006

  View details for PubMedID 3789207

• RECIDIVISM OF THE CRIMINALLY INSANE IN FRANCE - A 22-YEAR FOLLOW-UP JOURNAL OF CLINICAL PSYCHIATRY Yesavage, J. A., Benezech, M., LARRIEUARGUILLE, R., BOURGEOIS, M., Tanke, E., RAGER, P., Mills, M. 1986; 47 (9): 465-466

  Abstract

  Characteristics of 1096 recidivistic mentally ill criminal offenders admitted to a specialized hospital in France are described. All subjects were mentally ill and had been judged nonresponsible for an act of crime. Crimes against persons (murder or assault) accounted for 42% of the crimes for which these patients were admitted. The remaining causes of admission were crimes against property (theft) and "victimless" crimes. Subject files indicated a wide difference in cause of admission for violent acts among the different diagnostic categories. Although the frequency of readmission and violent acts at readmission did not change for the group as a whole, they did change between admissions for the different diagnostic groups. Results indicate that differences exist between diagnostic categories of mentally ill offenders in terms of not only the type of crime committed but also the likelihood of recidivism.

  View details for Web of Science ID A1986E195100005

  View details for PubMedID 3745128

• THYROTROPIN-RELEASING-HORMONE STIMULATION TEST AND ALZHEIMERS-DISEASE BIOLOGICAL PSYCHIATRY Peabody, C. A., Minkoff, J. R., Davies, H. D., Winograd, C. H., Yesavage, J., Tinklenberg, J. R. 1986; 21 (5-6): 553-556

  View details for Web of Science ID A1986A809900017

  View details for PubMedID 3083879

• PRIMING EFFECTS AND RECOGNITION MEMORY IN YOUNG AND ELDERLY ADULTS EXPERIMENTAL AGING RESEARCH Rose, T. L., Yesavage, J. A., Hill, R. D., Bower, G. H. 1986; 12 (1): 31-37

  Abstract

  The present study explores the effects of age on the priming of alternate homophone spellings and recognition memory. Sixteen young and sixteen elderly adults were given a general information test, a spelling test, and a test of recognition memory. By embedding the less frequently spelled member of different homophone units (e.g., write vs. right) in the general information questions, certain of the homophones were primed during this task. The effect of this priming was assessed through the subjects' choice of spelling for these words on the spelling test. Recognition memory was assessed by asking subjects to indicate which words from a longer list were presented during the spelling test. As found in prior research priming effects were observed in younger subjects; however, no significant priming effects occurred in the older age group. On the recognition test, homophones were more often correctly recognized than nonhomophones, and priming affected the scores of the young negatively, but had no effects, positive or negative, on the elderly. These results suggest possible differences in the underlying bases of memory loss in aged adults and amnesics.

  View details for Web of Science ID A1986A819100003

  View details for PubMedID 3709605

• Long-Term Efficacy of Cognitive Training for Age-Associated Memory Impairment: A Six-Month Follow-Up Study DEVELOPMENTAL NEUROPSYCHOLOGY Sheikh, J. I., Hill, R. D., Yesavage, J. A. 1986; 2 (4): 413-421

  View details for DOI 10.1080/87565648609540358

  View details for Web of Science ID 000209364000012

• A KNOWLEDGE ASSESSMENT TEST FOR GERIATRIC PSYCHIATRY HOSPITAL AND COMMUNITY PSYCHIATRY Sheikh, J. I., Yesavage, J. A. 1985; 36 (11): 1160-1166

  View details for Web of Science ID A1985ATT3700003

  View details for PubMedID 4065839

• PLASMA TESTOSTERONE LEVELS, DEPRESSION, SEXUALITY, AND AGE BIOLOGICAL PSYCHIATRY Yesavage, J. A., Davidson, J., WIDROW, L., Berger, P. A. 1985; 20 (2): 222-225

  View details for Web of Science ID A1985AMZ8700018

  View details for PubMedID 3971004

• EARLY PARENTAL DISCIPLINE AND ADULT SELF-DESTRUCTIVE ACTS JOURNAL OF NERVOUS AND MENTAL DISEASE Yesavage, J. A., WIDROW, L. 1985; 173 (2): 74-77

  Abstract

  Forty-five male inpatients with major depressive episodes by DSM-III criteria (296.2, 296.3, 296.5) were examined for correlates of inpatient self-destructive behavior. It was found that 44% of the variance for inpatient self-destructive acts could be accounted for by a combination of history of severe childhood discipline and parental conflict. Losses experienced during childhood were of less importance than these measures of family instability. Such information may be of use in the clinical prediction of self-destructive acts by depressed patients.

  View details for Web of Science ID A1985ABS4800002

  View details for PubMedID 3968549

• CORRELATIONS OF SELF-DIRECTED VIOLENCE IN ACUTE SCHIZOPHRENICS WITH CLINICAL RATINGS AND PERSONALITY MEASURES JOURNAL OF NERVOUS AND MENTAL DISEASE SEEMAN, K., Yesavage, J., WIDROW, L. A. 1985; 173 (5): 298-302

  Abstract

  Schizophrenic patients admitted to an acute inpatient unit were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS), items reflecting hostility from the same scale, the Eysenck Personality Questionnaire (EPQ), and the Socialization and Self-Control scales of the California Psychological Inventory (CPI). Incidents of violent and nonviolent suicidal behavior and suicidal ideation before admission, and assaultiveness against self subsequent to admission were recorded. It was determined that behavioral ratings of degree of schizophrenic symptoms on the CPRS are more highly likely than ratings of hostility to correlate with self-directed violence before and subsequent to admission. Personality measures that reflect violence toward others (Psychoticism on the EPQ and Socialization on the CPI) also correlate with violence toward self.

  View details for Web of Science ID A1985AGX0200011

  View details for PubMedID 3989519

• CHARACTERISTICS OF ASSAULTIVE PATIENTS WHO DO AND DO NOT PROVIDE VISIBLE CUES OF POTENTIAL VIOLENCE AMERICAN JOURNAL OF PSYCHIATRY Tanke, E. D., Yesavage, J. A. 1985; 142 (12): 1409-1413

  Abstract

  Twelve assaultive psychiatric patients who had provided visible cues (i.e., verbal threats) of potential violence were compared on Brief Psychiatric Rating Scale factor scores with 13 patients who had not provided such cues. These groups differed from one another and from a group of 253 nonassaultive patients on one or more of the following dimensions: thinking disorder, withdrawal-retardation, anxious depression, hostile-suspiciousness, and activation. In addition, the factor scores significantly predicted the occurrence of violence among patients who did not exhibit visible cues.

  View details for Web of Science ID A1985AVH1900003

  View details for PubMedID 4073302

• DESGLYCINAMIDE-9-ARGININE-8-VASOPRESSIN (DGAVP, ORGANON-5667) IN PATIENTS WITH DEMENTIA NEUROBIOLOGY OF AGING Peabody, C. A., Thiemann, S., PIGACHE, R., MILLER, T. P., Berger, P. A., Yesavage, J., Tinklenberg, J. R. 1985; 6 (2): 95-100

  Abstract

  Vasopressin peptides have been shown to facilitate learning and memory in both animals and humans; however, the effectiveness in humans is controversial. In a double blind parallel group study, 17 demented subjects (either Alzheimer's or alcoholic) were given either desglycinamide-9-arginine-8-vasopressin (DGAVP) 92 micrograms intranasally TID or an identical placebo for 1 week after having received 1 week of placebo. To our knowledge, this is the first report of DGAVP being used in subjects with dementia. The DGAVP group had a statistically significant improvement on the Buschke list learning of low imagery words. However, for various reasons discussed in the paper, we feel this finding needs to be replicated before any definite conclusions can be drawn. Since there were no other appreciable behavioral effects of this DGAVP regimen, our results should be considered negative. There was no evidence of any DGAVP-related adverse effects, except for possible weight gain.

  View details for Web of Science ID A1985ALA3700002

  View details for PubMedID 3895014

• PRELIMINARY COMMUNICATION - INTELLECTUAL DEFICIT AND SLEEP-RELATED RESPIRATORY DISTURBANCE IN THE ELDERLY SLEEP Yesavage, J., Bliwise, D., Guilleminault, C., Carskadon, M., Dement, W. 1985; 8 (1): 30-33

  Abstract

  Polysomnography and neuropsychological tests administered to 41 nondemented male subjects (mean age, 69.5) indicated that impaired performance was associated with sleep-related respiratory disturbance. Such deficits could reflect deficits in vigilance or cortical insult resulting from nightly hypoxemia. Whether the degree of impairment observed here predicts more severe dementia will await longitudinal studies.

  View details for Web of Science ID A1985ADX6500004

  View details for PubMedID 3992106

• NONPHARMACOLOGIC TREATMENTS FOR MEMORY LOSSES WITH NORMAL AGING AMERICAN JOURNAL OF PSYCHIATRY Yesavage, J. A. 1985; 142 (5): 600-605

  Abstract

  In a critical review of studies of training programs for elderly individuals with cognitive deficits, the author found that decrements of cognitive function with aging are not small. In 70-year-old normal individuals, losses are on the order of 20%-40%, depending on the process tested and the testing method. Although long-term effects are poorly documented, training programs for normal elderly individuals have been shown to improve selected cognitive processes, including memory, to about the same degree that some of these processes decline with aging.

  View details for Web of Science ID A1985AGG2500012

  View details for PubMedID 3885762

• FANTASIZED COMPANIONS AND SUICIDAL DEPRESSIONS - 2 CASE-REPORTS AMERICAN JOURNAL OF PSYCHOTHERAPY SEEMAN, K., WIDROW, L., Yesavage, J. 1984; 38 (4): 541-557

  Abstract

  Two acutely suicidal adult patients with fantasized companions integral to the formation of suicide intent are presented. The phenomenon of the fantasized companion is reviewed, differentiated from true hallucinatory or psychotic phenomena, and related to other fantasy and dissociative states, such as daydreaming and multiple personalities. In this regard, the concept of hysterical psychosis is discussed. The functions served by the fantasized companions and their involvement in the successful treatment of the patients are described.

  View details for Web of Science ID A1984TR29200009

  View details for PubMedID 6517172

• ERGOLOID MESYLATES FOR SENILE DEMENTIAS - UNANSWERED QUESTIONS ANNALS OF INTERNAL MEDICINE Hollister, L. E., Yesavage, J. 1984; 100 (6): 894-898

  Abstract

  Ergoloid mesylates has been used for 30 years to treat patients with senile dementia. Indications for this drug include hypertension, peripheral vascular disease, and senile dementia of the Alzheimer type. Formerly classified as a cerebral vasodilator, ergoloid mesylates is now considered a metabolic enhancer, but how this action pertains to treatment of senile dementia is uncertain. Prescribed doses of the drug range from 1.5 mg/d to as much as 12 mg/d, but the optimal dose is unknown. Although there is evidence of the short-term efficacy of ergoloid mesylates from numerous controlled trials, many clinicians still consider it to be a placebo. No alternative drug treatments have been proved better. The crucial decision a physician must make is whether to try specific drug therapy or rely solely on supportive care and symptomatic drug treatment. The increasing prevalence of senile dementia has renewed interest in discovering more effective drug treatments for this condition.

  View details for Web of Science ID A1984SV60900025

  View details for PubMedID 6372566

• HOMICIDE BY PSYCHOTICS IN FRANCE - A 5-YEAR STUDY JOURNAL OF CLINICAL PSYCHIATRY Benezech, M., Yesavage, J. A., ADDAD, M., BOURGEOIS, M., Mills, M. 1984; 45 (2): 85-86

  Abstract

  Records were reviewed for all psychotics who had been found not responsible for a homicide and admitted to a French state hospital for the criminally insane over a 5-year period (N = 109). Subjects were diagnosed primarily as schizophrenic (N = 64) or paranoid (N = 37). Paranoids were more likely than schizophrenics to have killed a relative or friend rather than a stranger or another mental patient (p less than .05), whereas schizophrenics were more likely than paranoids to have killed a parent than another relative or a friend (p less than .01). Homicide by schizophrenics commonly involved enmeshed parental relationships of delusional proportions; themes of jealously and megalomania predominated in homicides by paranoids.

  View details for Web of Science ID A1984SC23800009

  View details for PubMedID 6693367

• RACE, VIOLENCE, AND PSYCHOPATHOLOGY JOURNAL OF CLINICAL PSYCHIATRY Lawson, W. B., Yesavage, J. A., Werner, P. D. 1984; 45 (7): 294-297

  Abstract

  The frequency of violent behavior among inpatients on an acute psychiatric unit for veterans was examined. Violent behavior was assessed using a modified Lion scale in 93 white and 24 black consecutively admitted inpatients receiving a fixed dose of neuroleptic. Blacks were significantly less violent according to the Lion scale. Item analysis revealed that whites made more violent threats, committed more violent acts against self, and were more likely to be secluded or restrained. Blacks were less likely to commit multiple acts against others, although the actual numbers of violent episodes were not significantly different. No racial differences were seen in serum neuroleptic level, psychopathology as measured by the BPRS, or admission status. The same racial differences in violence were seen when either schizophrenics alone or paranoid schizophrenics were considered.

  View details for Web of Science ID A1984TB30000003

  View details for PubMedID 6735988

• ELECTROCONVULSIVE-THERAPY IN MASSACHUSETTS AMERICAN JOURNAL OF PSYCHIATRY Mills, M. J., PEARSALL, D. T., Yesavage, J. A., Salzman, C. 1984; 141 (4): 534-538

  Abstract

  A study of the use of electroconvulsive therapy in Massachusetts shows that between 1974 and 1980 ECT use decreased significantly in both public- and private-sector hospitals. This decline was particularly pronounced in public-sector hospitals. The average age of ECT-treated patients rose during the period; women received ECT more often than men; and bilateral ECT remained in more frequent use. Though ECT was most frequently prescribed for major depression, about 20% of those receiving it were diagnosed as having a dysthymic disorder. State regulation and advances in psychiatric treatment may partially explain the decrease in ECT use.

  View details for Web of Science ID A1984SK32400009

  View details for PubMedID 6703132

• PSYCHIATRISTS JUDGMENTS OF DANGEROUSNESS IN PATIENTS ON AN ACUTE CARE UNIT AMERICAN JOURNAL OF PSYCHIATRY Werner, P. D., Rose, T. L., Yesavage, J. A., SEEMAN, K. 1984; 141 (2): 263-266

  Abstract

  Statistical analyses suggest that psychiatrists emphasize hostility, agitation, previous assaultiveness, and suspiciousness as factors predictive of violence in psychiatric inpatients. When the actual correlates of violence in these patients are evaluated, a different picture of the assaultive inpatient emerges. Examination of differences between the cues emphasized by clinicians to make their predictions and the empirical correlates of violence suggests ways of improving the accuracy of clinical judgments of inpatients' dangerousness.

  View details for Web of Science ID A1984SA90600022

  View details for PubMedID 6691491

• SEMANTIC ELABORATION AND THE METHOD OF LOCI - A NEW TRIP FOR OLDER LEARNERS EXPERIMENTAL AGING RESEARCH Yesavage, J. A., Rose, T. L. 1984; 10 (3): 155-159

  Abstract

  The present study examined the effectiveness of two variations of a list learning mnemonic, the method of loci, on the recall of elderly subjects. In the Loci Only group (n = 20) subjects were instructed in the standard mnemonic and taught how to produce visual images associating each item to be remembered with one of several familiar locations. A second group, the Loci + Judgment condition (n = 17), received identical instructions except that they were taught, in addition, to make a personal judgment of the pleasantness of each visual image association. As predicted, subjects in the Loci Plus Judgment group showed greater improvement in their recall following instruction in the mnemonic. These results point to the importance of nonredundant forms of stimulus elaboration as a means of enhancing the accessibility of visual images and the effectiveness of visual mnemonic techniques.

  View details for Web of Science ID A1984TZ95100006

  View details for PubMedID 6519145

• MATHEMATICAL AND EMPIRICAL DEVELOPMENT OF A TEST OF MEMORY FOR CLINICAL AND RESEARCH USE PSYCHOLOGICAL BULLETIN Kraemer, H. C., Peabody, C. A., Tinklenberg, J. R., Yesavage, J. A. 1983; 94 (2): 367-380

  View details for Web of Science ID A1983RG39800007

• DIFFERENTIAL-EFFECTS OF VIETNAM COMBAT EXPERIENCES VS CRIMINALITY ON DANGEROUS BEHAVIOR BY VIETNAM VETERANS WITH SCHIZOPHRENIA JOURNAL OF NERVOUS AND MENTAL DISEASE YESAVAGE, J. A. 1983; 171 (6): 382–84

  Abstract

  Psychiatric patients with Vietnam combat experience have often been described as violent, and it has been hypothesized that their violence may be due either to Vietnam combat experiences or longstanding psychopathic tendencies, including criminality before entering the service. Criminal and military history of Vietnam era veterans diagnosed schizophrenic by DSM-III criteria were examined in relation to inpatient measures of assault. Seventy subjects were examined, of which 27 were in Vietnam and 19 of these 27 in combat. By using multiple regression techniques, it was determined that certain violent tendencies in schizophrenic Vietnam era veterans are better related to their war experiences than premorbid criminal behavior.

  View details for DOI 10.1097/00005053-198306000-00009

  View details for Web of Science ID A1983QU32300009

  View details for PubMedID 6854304

• RELIABILITY, ACCURACY, AND DECISION-MAKING STRATEGY IN CLINICAL-PREDICTIONS OF IMMINENT DANGEROUSNESS JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY Werner, P. D., Rose, T. L., Yesavage, J. A. 1983; 51 (6): 815-825

  View details for Web of Science ID A1983RS62200003

  View details for PubMedID 6655098

• FAMILY CONFLICT, PSYCHO-PATHOLOGY, AND DANGEROUS BEHAVIOR BY SCHIZOPHRENIC INPATIENTS PSYCHIATRY RESEARCH Yesavage, J. A., BECKER, J. M., Werner, P. D., PATTON, M. J., SEEMAN, K., BRUNSTING, D. W., Mills, M. J. 1983; 8 (4): 271-280

  Abstract

  Data supporting the hypothesis that history of severe discipline and parental conflict in childhood is related to current violence were obtained in a study of 100 schizophrenic inpatients. In addition to a relation between inpatient violence and degree of schizophrenic symptoms, inpatient assaults and other dangerousness measures were positively and significantly correlated with severity of parental discipline, especially involving the father, and with degree of family conflict, particularly fights between parents and others outside the home.

  View details for Web of Science ID A1983QQ85100004

  View details for PubMedID 6576393

• HOSTILE WORDS AND ASSAULTIVE BEHAVIOR ON AN ACUTE INPATIENT PSYCHIATRIC UNIT JOURNAL OF NERVOUS AND MENTAL DISEASE Werner, P. D., Yesavage, J. A., BECKER, J. M., BRUNSTING, D. W., Isaacs, J. S. 1983; 171 (6): 385-387

  Abstract

  This report analyzes the relationship of hostile verbalizations to assaultive acts committed by 110 male schizophrenic patients on an acute psychiatric unit. It was found that patients who were verbally assaultive and threatening also tended to be physically assaultive. Assaults rarely occurred in the absence of verbal threats or abuse, and 32 per cent of violent patients could be identified on the basis of the occurrence of hostile verbalizations.

  View details for Web of Science ID A1983QU32300010

  View details for PubMedID 6854305

• CONCURRENT VALIDITY OF THE OVER-CONTROLLED HOSTILITY SCALE FOR PSYCHOTICS PSYCHOLOGICAL REPORTS Werner, P. D., BECKER, J. M., Yesavage, J. A. 1983; 52 (1): 93-94

  View details for Web of Science ID A1983QJ05100016

  View details for PubMedID 6844509

• CONTINUING CASE LAW DEVELOPMENT IN THE RIGHT TO REFUSE TREATMENT AMERICAN JOURNAL OF PSYCHIATRY Mills, M. J., Yesavage, J. A., Gutheil, T. G. 1983; 140 (6): 715-719

  View details for Web of Science ID A1983QS27500008

  View details for PubMedID 6846630

• ARSON IN MENTALLY-ILL AND CRIMINAL POPULATIONS JOURNAL OF CLINICAL PSYCHIATRY Yesavage, J. A., Benezech, M., Ceccaldi, P., BOURGEOIS, M., ADDAD, M. 1983; 44 (4): 128-130

  Abstract

  Two groups of adult arsonists, 27 with mental illness and 23 not considered to be mentally ill, were examined for demographic features, premorbid factors, motives, and family background. Almost half (46%) of the mentally ill arsonists were mentally retarded. A large proportion of the not-mentally-ill group committed arson as a "crime of passion," 33% of which occurred under the influence of alcohol. Both groups reported a high proportion of absent fathers and seriously disturbed family relations. The relationship of these acts to sexual impulses was found to be minimal, a finding that contrasts with case report studies.

  View details for Web of Science ID A1983QK64400002

  View details for PubMedID 6833197

• CONCENTRATION AND MNEMONIC TRAINING IN ELDERLY SUBJECTS WITH MEMORY COMPLAINTS - A STUDY OF COMBINED THERAPY AND ORDER EFFECTS PSYCHIATRY RESEARCH Yesavage, J. A., Rose, T. L. 1983; 9 (2): 157-167

  Abstract

  In a study of a cognitive retraining program for the elderly, subjects received a combination of two types of training designed to reduce the memory impairment associated with normal aging. Concentration training (CT) consisted of techniques to improve selective and sustained attention. Mnemonic training (MT) involved an associative imagery technique designed to enhance the organization and retrieval of information. Order effects were examined using two groups of subjects. One group received CT followed by MT whereas the other group received MT before CT. It was hypothesized that the CT-MT sequence would improve immediate and delayed serial recall more than the reverse sequence. This hypothesis was supported and transfer effects were found on a paired-associates learning task. The findings suggest a need for further research on potential interactions and sequencing effects among different forms of cognitive training.

  View details for Web of Science ID A1983RB16200008

  View details for PubMedID 6578527

• DEVELOPMENT AND VALIDATION OF A GERIATRIC DEPRESSION SCREENING SCALE - A PRELIMINARY-REPORT JOURNAL OF PSYCHIATRIC RESEARCH Yesavage, J. A., Brink, T. L., Rose, T. L., LUM, O., Huang, V., ADEY, M., Leirer, V. O. 1983; 17 (1): 37-49

  View details for Web of Science ID A1983QQ74400004

• HISTORY OF DRUG-ABUSE AND DANGEROUS BEHAVIOR IN INPATIENT SCHIZOPHRENICS JOURNAL OF CLINICAL PSYCHIATRY Yesavage, J. A., Zarcone, V. 1983; 44 (7): 259-261

  Abstract

  The alcohol and drug use histories of 85 schizophrenic inpatients were examined in relation to measures of dangerousness while in hospital (physical and verbal assaults and episodes of seclusion and restraint). Stepwise multiple regression analyses showed significant relationships between each dangerousness measure and certain drug abuse history factors. Assault was most closely related to a drug abuse factor containing a history of blackout episodes and assaultiveness while drinking, whereas seclusion and restraint were most closely related to histories of becoming "loud" while on drugs. Overall measures of dangerousness appear to relate best to histories of becoming loud or assaultive while taking drugs.

  View details for Web of Science ID A1983QZ82900006

  View details for PubMedID 6863226

• COMPUTERIZED PSYCHOLOGICAL-TESTS - TESTS OF ATTENTION, MEMORY AND MOTOR-PERFORMANCE IN GERIATRIC RESEARCH PRESSE MEDICALE Yesavage, J. A., Tinklenberg, J. R. 1983; 12 (48): 3170-3172

  Abstract

  The purpose of this paper is to present certain psychological tests adapted for computerized testing of subjects. The reasons why we have considered such tests are numerous: computerized test facilitate measurement of reaction time, testing conditions are standardized without reliance on performance of research assistants, data can be recorded on disc storage without paper handling, preliminary analyses and individual results can be available immediately after testing, simulation of certain real-life situations is possible, randomization of testing materials is facilitated. The computerized testing paradigms for use in gerontology to be discussed are: one an attention task of possible use in psychological research; the second a memory task aimed at basic cognitive psychological research and finally a performance task relating to a complex motor ability (flying). All provide inexpensive, reliable, quantified data and all use the same hardware. It is expected that this area will expand enormously and rapidly.

  View details for Web of Science ID A1983RX04000030

  View details for PubMedID 6228935

• INTERACTIVE IMAGERY AND AFFECTIVE JUDGMENTS IMPROVE FACE-NAME LEARNING IN THE ELDERLY JOURNALS OF GERONTOLOGY Yesavage, J. A., Rose, T. L., Bower, G. H. 1983; 38 (2): 197-203

  Abstract

  Groups of elderly adults were taught to learn name-to-face associations using one of three different techniques. In a control group (no image) participants were taught for each face-name pair to select a prominent facial feature and to transform the surname into a concrete word. Persons in a second group (image) additionally were taught to employ interactive imagery to form an association between the prominent feature and the transformed name. The third group (image + judgment) was treated the same as the second except that these individuals were also taught to judge the pleasantness of the image association that was formed. As predicted, improvement following instruction was minimal when no image association was formed but strong when interactive imagery was used. Moreover, those persons in the image + judgment group remembered more names than those in the image group and showed less forgetting on a measure of delayed recall. In addition to replicating and extending the findings of previous research with a different sample, the present study demonstrates that semantic orienting tasks can be used to enhance the retention of visual image associations as well as the simpler stimuli used in prior research.

  View details for Web of Science ID A1983QG28300009

  View details for PubMedID 6827036

• AUDITORY VERSUS MEMORY DEFICITS IN PARANOID AND CHRONIC UNDIFFERENTIATED SCHIZOPHRENIA JOURNAL OF PSYCHIATRIC TREATMENT AND EVALUATION Yesavage, J. A., PORTNOFF, L. A., Rose, T. L. 1983; 5 (4): 309-314

  View details for Web of Science ID A1983RH92600002

• DIFFERENTIAL-EFFECTS OF A LIST-LEARNING MNEMONIC IN 3 AGE-GROUPS GERONTOLOGY Rose, T. L., Yesavage, J. A. 1983; 29 (5): 293-298

  Abstract

  The effectiveness of a list-learning mnemonic was assessed across a wide range of ages. Young, middle-aged, and older adults attended a 3-day course in which a modified version of the method of loci was taught. Tests of free recall were administered at the beginning and end of the course. All three age groups displayed significantly better recall following instruction in the mnemonic than they did initially; however, the amount of improvement was less in older subjects than younger ones. These results, though indicating the mnemonic to be effective for young and old alike, suggest the development of encoding and retrieval deficits with age.

  View details for Web of Science ID A1983RE17000001

  View details for PubMedID 6618184

• [Correlations between modes of internment and aggressive behavior in a California psychiatric unit]. Annales medico-psychologiques Yesavage, J., Benezech, M., BOURGEOIS, M., Mills, M. 1982; 140 (7): 770-776

  View details for PubMedID 7168514

• RELAXATION TRAINING AND MEMORY IMPROVEMENT IN ELDERLY NORMALS - CORRELATION OF ANXIETY RATINGS AND RECALL IMPROVEMENT EXPERIMENTAL AGING RESEARCH Yesavage, J. A., Rose, T. L., Spiegel, D. 1982; 8 (3-4): 195-198

  View details for Web of Science ID A1982PR75100012

  View details for PubMedID 6762966

• PHARMACOLOGIC CHARACTERISTICS OF MEIGE DYSTONIA - DIFFERENTIATION FROM TARDIVE-DYSKINESIA JOURNAL OF CLINICAL PSYCHIATRY Stahl, S. M., Yesavage, J. A., Berger, P. A. 1982; 43 (11): 445-446

  Abstract

  Idiopathic orofacial dyskinesia, also called Brueghel's syndrome, blepharospasm-oromandibular dystonia, and Meige dystonia, is characterized by involuntary facial movements. Since this disorder can be difficult to distinguish from tardive dyskinesia, we have generated a neuropharmacologic profile of Meige dystonia. Symptoms were improved by antagonists of both dopamine and acetylcholine and worsened by the cholinergic agonist physostigmine, consistent with a hypothesis of relative excess in both dopamine and acetylcholine neuronal activities. Since tardive dyskinesia is hypothesized to be characterized by dopamine excess and acetylcholine deficiency, a physostigmine infusion may help differentiate these two disorders by exacerbating Meige dystonia but improving tardive dyskinesia.

  View details for Web of Science ID A1982PR25000004

  View details for PubMedID 7174619

• THE CONTEXT OF INVOLUNTARY COMMITMENT ON THE BASIS OF DANGER TO OTHERS - A STUDY OF THE USE OF THE CALIFORNIA 14-DAY CERTIFICATE JOURNAL OF NERVOUS AND MENTAL DISEASE Yesavage, J. A., Werner, P. D., BECKER, J. M., Mills, M. J. 1982; 170 (10): 622-627

  Abstract

  This study examines the applications of civil commitment criteria for prolonged (14-day) involuntary hospitalization of individuals judged to be dangerous to others by reason of mental illness. The California Civil Commitment Statute (Lanterman-Petris-Short, LPS) provides for such commitment, after a 72-hour period of observations. For a sample of 71 males on an acute inpatient unit, we examined the relationship between 14-day certification by reason of dangerousness to others (DO) under the LPS and measures of prehospitalization dangerousness, prior legal status, assaultive behavior in hospital, and mental status. The 31 per cent of subjects who were certified as DO were found to have been significantly more often held initially for 72-hour observation on the DO grounds than were patients who were certified for other reasons. However, subjects in the DO group were no different from the contrast groups on ratings of assaultiveness of preadmission behavior and of violent acts while in hospital. The implications of these results for the evaluation of civil commitment proceedings are discussed.

  View details for Web of Science ID A1982PJ07000006

  View details for PubMedID 7108497

• DRIFT AND DANGEROUSNESS - SOCIAL-CLASS DIFFERENCES BETWEEN ACUTE SCHIZOPHRENICS AND THEIR PARENTS IN RELATION TO MEASURES OF VIOLENCE BRITISH JOURNAL OF PSYCHIATRY Yesavage, J. A., Werner, P. D., BECKER, J. M., SEEMAN, K. 1982; 141 (SEP): 267-270

  Abstract

  Socio-economic differences between schizophrenics on an acute in-patient unit and their parents were studied in relation to indices of dangerousness and of psychiatric status. It was found that, whenever thier class of origin, a large proportion of patients had dropped in occupational attainment, relative to that of their parents, but that patients tended to be higher in education than their parents. Patients who had committed an assaultive act prior to admission were lower in social status than their parents.

  View details for Web of Science ID A1982PH07900009

  View details for PubMedID 7139209

• CEREBROSPINAL-FLUID LACTATE LEVELS AND AGING - FINDINGS IN NORMALS AND PATIENTS WITH MAJOR DEPRESSIVE-DISORDERS GERONTOLOGY Yesavage, J. A., HOLMAN, C. A., Berger, P. A. 1982; 28 (6): 377-380

  View details for Web of Science ID A1982PY65100005

  View details for PubMedID 7160625

• SHORT-TERM CIVIL COMMITMENT AND THE VIOLENT PATIENT AMERICAN JOURNAL OF PSYCHIATRY Yesavage, J. A., Werner, P. D., BECKER, J. M., Mills, M. J. 1982; 139 (9): 1145-1149

  Abstract

  To explore the specificity of criteria for civil commitment for dangerousness, the authors examined the relationship between civil commitment for dangerousness to others under the California Civil Commitment Statute (the Lanterman-Petris-Short Act) and violent acts and behavioral ratings made immediately after commitment. Using a prospective design they evaluated 84 subjects. The ratings of violent acts for subjects considered dangerous to others were no different than those of a nondangerous control group. The subjects considered dangerous to others, however, differed on several subscales of the Brief Psychiatric Rating Scale. The authors discuss the implications of these results for civil commitment proceedings.

  View details for Web of Science ID A1982PE50400011

  View details for PubMedID 7114307

• ANALYSIS OF RESPONSES TO THE PERSONAL OPINION SURVEY BY A SAMPLE OF INPATIENTS PSYCHOLOGICAL REPORTS Werner, P. D., BECKER, J. M., Yesavage, J. A., Isaacs, J. S. 1982; 51 (2): 423-429

  View details for Web of Science ID A1982PK72100021

  View details for PubMedID 7178347

• SERUM LEVEL MONITORING OF THIOTHIXENE IN SCHIZOPHRENIA - ACUTE SINGLE-DOSE LEVELS AT FIXED DOSES AMERICAN JOURNAL OF PSYCHIATRY Yesavage, J. A., Becker, J., Werner, P. D., Mills, M. J., HOLMAN, C. A., Cohn, R. 1982; 139 (2): 174-178

  Abstract

  After establishing a strong correlation between steady-state thiothixene levels and levels drawn 2.5 hours after a 20-mg test dose, the authors examined the correlation between clinical improvement and serum levels drawn 2.5 hours after a single 20-mg test dose of thiothixene. For 30 male schizophrenic inpatients, improvement on the Brief Psychiatric Rating Scale was significantly correlated with the single test-dose levels. Serum levels were also positively correlated with age, which may explain the tendency of elderly patients to require lower neuroleptic doses and to exhibit a higher incidence of side effects. The results suggest that acute single-dose levels may be useful in predicting clinical response to thiothixene.

  View details for Web of Science ID A1982MZ70800003

  View details for PubMedID 7055286

• ELEVATION OF CEREBROSPINAL-FLUID LACTATE WITH AGING IN SUBJECTS WITH NORMAL BLOOD-OXYGEN SATURATIONS JOURNALS OF GERONTOLOGY Yesavage, J. A., HOLMAN, C. A., SARNQUIST, F. H., Berger, P. A. 1982; 37 (3): 313-315

  Abstract

  It has been hypothesized that cerebral oxidative glucose metabolism may become impaired with age and lead to deterioration of neuronal function. One marker of impaired cerebral oxidative glucose metabolism is increased cerebrospinal fluid (CSF) lactate. Prior studies have found an increase in CSF lactate in aged normals, but these studies have not controlled for the possibility that decreased respiratory function with age may lead to hypoxemia and increased CSF lactate. The current study measured peripheral blood oxygen saturations in 11 subjects during collection of CSF and documented that the increase in CSF lactate observed was not due to peripheral hypoxemia. Thus, increased CSF lactate with age appears to be of central origin.

  View details for Web of Science ID A1982NN31600010

  View details for PubMedID 7069154

• A COMPARISON OF MULTIPLE AND SINGLE ELECTROCONVULSIVE-THERAPY JOURNAL OF CLINICAL PSYCHIATRY Berens, E. S., Yesavage, J. A., Leirer, V. O. 1982; 43 (4): 126-128

  Abstract

  In a retrospective study of 30 patients receiving either single ECT (N = 17) or multiple monitored ECT (N = 13), no difference in effectiveness or safety was seen between treatments. However, patients who received multiple monitored ECT had fewer sessions of general anesthesia and a significantly more rapid course of treatment.

  View details for Web of Science ID A1982NK44600001

  View details for PubMedID 7068541

• SOMATOFORM DISORDERS - DIFFERENTIATION OF CONVERSION, HYPOCHONDRIACAL, PSYCHOPHYSIOLOGIC, AND RELATED DISORDERS POSTGRADUATE MEDICINE Brink, T. L., Yesavage, J. A. 1982; 72 (1): 189-?

  View details for Web of Science ID A1982NW77700025

  View details for PubMedID 7088743

• EFFECT OF NAFRONYL ON LACTATE AND PYRUVATE IN THE CEREBROSPINAL-FLUID OF PATIENTS WITH SENILE DEMENTIA JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yesavage, J. A., Tinklenberg, J. R., Hollister, L. E., Berger, P. A. 1982; 30 (2): 105-108

  Abstract

  In a single-blind study, 12 men (mean age 63 years) with senile dementia were given nafronyl in a dosage of 100 mg eight times daily for a week, followed by 100 mg four times daily for 12 weeks. Rigorous clinical, laboratory and psychometric assessments revealed no toxicity and no significant effects on vital functions. In the cerebrospinal fluid, the ratio of lactate to pyruvate decreased--a finding consistent with an increase in the aerobic metabolism of glucose.

  View details for Web of Science ID A1982NF70700005

  View details for PubMedID 6173407

• Development and validation of a geriatric depression screening scale: a preliminary report. Journal of psychiatric research Yesavage, J. A., Brink, T. L., Rose, T. L., LUM, O., Huang, V., ADEY, M., Leirer, V. O. 1982; 17 (1): 37-49

  Abstract

  A new Geriatric Depression Scale (GDS) designed specifically for rating depression in the elderly was tested for reliability and validity and compared with the Hamilton Rating Scale for Depression (HRS-D) and the Zung Self-Rating Depression Scale (SDS). In constructing the GDS a 100-item questionnaire was administered to normal and severely depressed subjects. The 30 questions most highly correlated with the total scores were then selected and readministered to new groups of elderly subjects. These subjects were classified as normal, mildly depressed or severely depressed on the basis of Research Diagnostic Criteria (RDC) for depression. The GDS, HRS-D and SDS were all found to be internally consistent measures, and each of the scales was correlated with the subject's number of RDC symptoms. However, the GDS and the HRS-D were significantly better correlated with RDC symptoms than was the SDS. The authors suggest that the GDS represents a reliable and valid self-rating depression screening scale for elderly populations.

  View details for PubMedID 7183759

• SINGLE-CASE STUDY OF CLINICAL-RESPONSE TO HIGH-DOSE ERGOT ALKALOID TREATMENT FOR DEMENTIA - PRELIMINARY-REPORT GERONTOLOGY Yesavage, J. A., Tinklenberg, J. R. 1981; 27 (1-2): 76-78

  View details for Web of Science ID A1981LD65900011

  View details for PubMedID 7215823

• INPATIENT EVALUATION OF AGGRESSION IN PSYCHIATRIC-PATIENTS JOURNAL OF NERVOUS AND MENTAL DISEASE Yesavage, J. A., Werner, P. D., Becker, J., Holman, C., Mills, M. 1981; 169 (5): 299-302

  Abstract

  The authors rated violent and violence-related behavior of patients on a psychiatric intensive care unit, and found that despite the restricted environment such behaviour was manifested to a considerable degree. The amount of violent behavior was significantly correlated with admission Brief Psychiatric Rating Scale ratings on measures of thought disorder and schizophrenic thinking, but not with ratings of hostility.

  View details for Web of Science ID A1981LN90300006

  View details for PubMedID 7217940

• CRIMINAL ACTS AMONG SCHIZOPHRENICS IN FRENCH MENTAL-HOSPITALS JOURNAL OF NERVOUS AND MENTAL DISEASE ADDAD, M., Benezech, M., BOURGEOIS, M., Yesavage, J. 1981; 169 (5): 289-293

  Abstract

  This paper reports a questionnaire study of 116 schizophrenic subjects. A group without history of crime (N = 53) was found to have considerably better relations with their families than a group with histories of criminal acts (N = 63). An interesting finding was that negative relations with the father were reported more frequently in the noncriminal group than in the criminal group, whereas negative relations with the mother were more frequent in the criminal group than in the noncriminal group. Within the criminal group several differences were found between the criminal behavior of chronic undifferentiated and paranoid schizophrenics. Although subjects of both diagnoses often acted with premeditation, paranoid schizophrenics were more likely to commit crimes against persons, to be under the influence of their illness during the crime, to be secretive about plans, to admit their guilt, and to cite vengeance as a motive than chronic undifferentiated schizophrenic subjects.

  View details for Web of Science ID A1981LN90300004

  View details for PubMedID 7217938

• VISUAL-SEARCH PERFORMANCE BY PARANOID AND CHRONIC UNDIFFERENTIATED SCHIZOPHRENICS PERCEPTUAL AND MOTOR SKILLS PORTNOFF, L. A., Yesavage, J. A., Acker, M. B. 1981; 53 (2): 411-418

  Abstract

  Disturbances in attention are among the most frequent cognitive abnormalities in schizophrenia. Recent research has suggested that some schizophrenics have difficulty with visual tracking, which is suggestive of attentional deficits. To investigate differential visual-search performance by schizophrenics, 15 chronic undifferentiated and 15 paranoid schizophrenics were compared with 15 normals on two tests measuring visual search in a systematic and an unsystematic stimulus mode. Chronic schizophrenics showed difficulty with both kinds of visual-search tasks. In contrast, paranoids had only a deficit in the systematic visual-search task. Their ability for visual search in an unsystematized stimulus array was equivalent to that of normals. Although replication and cross-validation is needed to confirm these findings, it appears that the two tests of visual search may provide a useful ancillary method for differential diagnosis between these two types of schizophrenia.

  View details for Web of Science ID A1981MR36800018

  View details for PubMedID 7312527

• CANNIBALISM AND VAMPIRISM IN PARANOID SCHIZOPHRENIA JOURNAL OF CLINICAL PSYCHIATRY Benezech, M., BOURGEOIS, M., BOUKHABZA, D., Yesavage, J. 1981; 42 (7): 290-290

  View details for Web of Science ID A1981LX46000007

  View details for PubMedID 7240115

• PHARMACOLOGICAL TREATMENT OF SENILE DEMENTIA IN THE USA AND EUROPE ANNALES MEDICO-PSYCHOLOGIQUES Yesavage, J. A., Tinklenberg, J. R., Berger, P. A., Masson, J. M., Martin, A., BOURGEOIS, M. 1981; 139 (1): 21-28

  Abstract

  This article is a review of the pharmacotherapy of senile dementia in Europe and the United States. Neurophysiological and neuropathological studies of demented elderly have suggested that a change from the attempt to improve cerebral blood flow to the attempt to improve neuronal intermediary (glycolytic) metabolism may be more fruitful therapeutically. Clinical studies of drugs which are direct smooth relaxant vasodilators are compared with studies of drugs claimed to improve neuronal intermediary metabolism in order to test this hypothesis. Comparison of 102 clinical studies of these two types of medications finds that a significant (p less than .005) number of studies of drugs with metabolic action claim positive results than to studies of drugs with vasodilatator action alone. Three new studies addressing questions of dose and spinal fluid effects of these medications are presented. Two studies provide evidence for the superiority of 6 mg/day of dihydroergotoxine mesylate to 3 mg/kg in the elderly. One study suggests that the medication naftidrofuryl, in doses of 800 mg/day and 400 mg/day, may have similar effects.

  View details for Web of Science ID A1981LS58000003

  View details for PubMedID 7020520

• DESIGN ASPECTS OF STUDIES OF DRUGS CLAIMED TO IMPROVE COGNITIVE FUNCTION IN THE AGED JOURNAL OF PSYCHIATRIC TREATMENT AND EVALUATION Yesavage, J. A., ADEY, M. 1981; 3 (6): 545-549

  View details for Web of Science ID A1981MT92700008

• ACUTE PHENCYCLIDINE (PCP) INTOXICATION - QUANTITATIVE URINE LEVELS AND CLINICAL MANAGEMENT AMERICAN JOURNAL OF PSYCHIATRY Walker, S., Yesavage, J. A., Tinklenberg, J. R. 1981; 138 (5): 674-675

  View details for Web of Science ID A1981LN47000021

  View details for PubMedID 6112883

• DEVELOPMENT OF A GERIATRIC BEHAVIORAL SELF-ASSESSMENT SCALE JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yesavage, J. A., ADEY, M., Werner, P. D. 1981; 29 (6): 285-288

  Abstract

  Described is the development of a self-rating geriatric behavioral scale modeled after the Sandoz Clinical Assessment-Geriatric (SCAG). This new Self-Assessment Scale-Geriatric (SASG) provides a valid and reliable measure of behavioral pathologic changes for the selective screening of elderly patients who manifest mile to moderate symptoms of dementia. Further use and refinement of this new measuring device are required to confer on it the maximum possible accuracy.

  View details for Web of Science ID A1981LT40500009

  View details for PubMedID 7195410

• Design aspects of clinical trials with ergot alkaloids: a comparison of two geriatric behavioral rating scales. Advances in biochemical psychopharmacology Yesavage, J. A., ADEY, M. 1980; 23: 357-362

  View details for PubMedID 7395622

• MULTIPLE MONITORED ELECTROCONVULSIVE-THERAPY IN THE ELDERLY JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yesavage, J. A., Berens, E. S. 1980; 28 (5): 206-209

  Abstract

  Twenty patients aged 45 or older with the diagnosis of endogenous depression were evaluated in terms of safety and efficacy in their response to multiple monitored electroconvulsive therapy (MMECT) versus single electroconvulsive therapy (SECT). The MMECT group (10 patients) when compared retrospectively with the control SECT group (10 patients) showed a similar record for safety and efficacy. However, the MMECT group required shorter overall duration of treatment, fewer sessions of general anesthesia, and lower dosages of anesthetic agents. The chief benefit of MMECT probably is in the reduction of the time the patient is at risk for suicide.

  View details for Web of Science ID A1980JS34400003

  View details for PubMedID 7365183

• CORRELATION OF CEREBROSPINAL-FLUID LACTATE WITH AGE AMERICAN JOURNAL OF PSYCHIATRY Yesavage, J., Berger, P. A. 1980; 137 (8): 976-977

  View details for Web of Science ID A1980KC80200022

  View details for PubMedID 7416305

• THE DEFENSIVE PRACTICE OF PSYCHIATRY ANNALES MEDICO-PSYCHOLOGIQUES BOURGEOIS, M., Yesavage, J., Benezech, M., Mas, F. 1980; 138 (5): 566-574

  View details for Web of Science ID A1980KL12000005

  View details for PubMedID 7436219

• CHOLINE CHLORIDE TREATMENT OF MEMORY DEFICITS IN THE ELDERLY AMERICAN JOURNAL OF PSYCHIATRY Mohs, R. C., Davis, K. L., Tinklenberg, J. R., Hollister, L. E., Yesavage, J. A., KOPELL, B. S. 1979; 136 (10): 1275-1277

  Abstract

  Eight elderly patients with mild memory impairment were given choline chloride, a drug that increases brain acetylcholine concentrations. After 16 g/day of choline for 7 days, average memory performance was not different from performance during pre- and postcholine placebo treatment, although the patient with the poorest baseline performance improved considerably on choline.

  View details for Web of Science ID A1979HN59900005

  View details for PubMedID 484722

• DIHYDROERGOTOXINE - 6-MG VERSUS 3-MG DOSAGE IN THE TREATMENT OF SENILE DEMENTIA - PRELIMINARY-REPORT JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yesavage, J. A., Hollister, L. E., Burian, E. 1979; 27 (2): 80-82

  Abstract

  In 14 patients with senile dementia, a study was made of two dosage levels (3 mg or 6 mg daily) of dihydroergotoxine mesylate (DEM, Hydergine). Only a nonstatistically significant trend was found for superiority of the higher dosage. However, one patient showed remarkable clinical improvement during the 6-mg period; the mechanism remains unexplained. Further studies are needed with this higher dosage in less impaired patients and in those with well-defined cerebral pathologic changes.

  View details for Web of Science ID A1979GJ53800005

  View details for PubMedID 762369

• VASODILATORS IN SENILE DEMENTIAS - REVIEW OF THE LITERATURE ARCHIVES OF GENERAL PSYCHIATRY Yesavage, J. A., Tinklenberg, J. R., Hollister, L. E., Berger, P. A. 1979; 36 (2): 220-223

  Abstract

  The rationale for the use of vasodilators in the aged has changed from the attempt to increase cerebral blood flow to the attempt to improve cerebral metabolism. Review of 102 studies of eight vasodilators showed that significantly more controlled studies claimed practical clinical benefit from drugs supposed to improve neuronal intermediary metabolism with secondary vasodilatation than from drugs supposed to have only vasodilator action (P less than .005). Studies of both classes of drugs often suffered from poor study design, inappropriate and inconsistent application of outcome measurements, as well as negative bias due to selection of severely demented subjects. Future studies should be placebo-controlled investigations of drugs with primarily metabolic action, address questions of dose and time response, consistently use appropriate outcome measurement, and concentrate on the elderly in whom cognitive improvement is possible.

  View details for Web of Science ID A1979GL00500012

  View details for PubMedID 420543

• PSYCHOPATHOLOGY AND TREATMENT OF VIOLENT PSYCHOPATHS IN THE USA ANNALES MEDICO-PSYCHOLOGIQUES Yesavage, J., FILL, N., Lapp, D., Becker, J., Mills, M., BOURGEOIS, M. 1979; 137 (8): 760-763

  View details for Web of Science ID A1979HU46600006

  View details for PubMedID 534399

• REPERTORY GRID AND BIOCHEMICAL CHARACTERIZATION OF DEPRESSION - COMPARISON OF CASE-REPORTS JOURNAL OF CLINICAL PSYCHIATRY Yesavage, J. A., Slater, P., Berger, P. A. 1979; 40 (5): 232-235

  Abstract

  Two cases of depression are presented: One which responded to psychotherapy and the other which responded to medication. These cases were evaluated by repertory grid analysis and by biochemical analysis. These results serve as the basis for a discussion of the use of such analysis as predictors of response in depression to psychotherapy or medication.

  View details for Web of Science ID A1979GW46600007

  View details for PubMedID 438147

• POSSIBLE ORGANOPHOSPHATE-INDUCED PARKINSONISM JOURNAL OF NERVOUS AND MENTAL DISEASE Davis, K. L., Yesavage, J. A., Berger, P. A. 1978; 166 (3): 222-225

  View details for Web of Science ID A1978ES56300010

• LOW-DOSE LEVODOPA IN SCHIZOPHRENIA COMMUNICATIONS IN PSYCHOPHARMACOLOGY Calil, H. M., Yesavage, J. A., Hollister, L. E. 1977; 1 (6): 593-596

  View details for Web of Science ID A1977EM88700010

  View details for PubMedID 608330