Academic Appointments


Clinical Trials


  • Examining the Effectiveness of Deep TMS in Veterans With Alcohol Use Disorder Not Recruiting

    This study aims to evaluate the efficacy of deep transcranial magnetic stimulation (dTMS) as a treatment for Veterans with an alcohol use disorder (AUD).

    Stanford is currently not accepting patients for this trial. For more information, please contact Eileen Grace Fischer, 650-493-5000.

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All Publications


  • A pilot, randomized clinical trial: Left dorsolateral prefrontal cortex intermittent theta burst stimulation improves treatment outcomes in veterans with alcohol use disorder. Alcohol, clinical & experimental research Padula, C. B., McCalley, D. M., Tenekedjieva, L., MacNiven, K., Rauch, A., Morales, J. M., Knutson, B., Humphreys, K., Williams, L. M., Durazzo, T. C. 2024; 48 (1): 164-177

    Abstract

    BACKGROUND: Transcranial magnetic stimulation (TMS) offers a promising treatment avenue to modulate brain function in alcohol use disorder (AUD). To the best of our knowledge, this pilot study is the first randomized, double-blind, sham-controlled trial to deliver intermittent theta burst stimulation to the left dorsolateral prefrontal cortex (DLPFC) among US veterans with AUD. We hypothesized that 20 sessions of real TMS are tolerable and feasible. As a secondary line of inquiry, we hypothesized that, relative to sham TMS, individuals receiving real TMS would experience greater reductions in 6-month relapse rates, anhedonia, and alcohol cue-reactivity.METHODS: Veterans (n=17, one woman) were enrolled in a double-blind, sham-controlled trial (2-3 sessions/day; 7-10days; 600 pulses/session; 20 sessions). Pre- and posttreatment assessments included responses to self-report questionnaires and functional magnetic resonance imaging measures of alcohol cue-reactivity. Alcohol consumption was assessed for 6months. Linear mixed-effects models were constructed to predict posttreatment craving, mood, and cue-reactivity.RESULTS: Individuals who received active iTBS (n=8) were less likely to relapse within 3months after treatment than the sham-treated group (n=9) (OR=12.0). Greater reductions in anhedonia were observed following active iTBS (Cohen's d=-0.59), relative to sham (d=-0.25). Alcohol cue-reactivity was reduced following active iTBS and increased following sham within the left insula (d=-0.19 vs. 0.51), left thalamus (d=-0.28 vs. 0.77), right insula (d=0.18 vs. 0.52), and right thalamus (d=-0.06 vs. 0.62).CONCLUSIONS: Relative to sham, we demonstrate that 20 sessions of real left DLPFC iTBS reduced the likelihood of relapse for at least 3months. The potential utility of this approach is underscored by observed decreases in anhedonia and alcohol cue-reactivity-strong predictors of relapse among veterans. These initial data offer a valuable set of effect sizes to inform future clinical trials in this patient population.

    View details for DOI 10.1111/acer.15224

    View details for PubMedID 38197808

  • BDNF rs6265 Met carriers with alcohol use disorder show greater age-related decline of N-acetylaspartate in left dorsolateral prefrontal cortex. Drug and alcohol dependence Durazzo, T. C., McNerney, M. W., Hansen, A. M., Gu, M., Sacchet, M. D., Padula, C. B. 2023; 248: 109901

    Abstract

    BACKGROUND: Brain-derived neurotrophic factor (BDNF) is implicated in neuronal and glial cell growth and differentiation, synaptic plasticity, and apoptotic mechanisms. A single-nucleotide polymorphism of the BDNF rs6265 gene may contribute to the pattern and magnitude of brain metabolite abnormalities apparent in those with an Alcohol Use Disorder (AUD). We predicted that Methionine (Met) carriers would demonstrate lower magnetic resonance spectroscopy (MRS) measures of N-acetylaspartate level (NAA) and greater age-related decline in NAA than Valine (Val) homozygotes.METHODS: Veterans with AUD (n=95; 46±12 years of age, min = 25, max = 71) were recruited from VA Palo Alto residential treatment centers. Single voxel MRS, at 3 Tesla, was used to obtain NAA, choline (Cho) and creatine (Cr) containing compounds from the left dorsolateral prefrontal cortex (DLPFC). Metabolite spectra were fit with LC Model and NAA and Cho were standardized to total Cr level and NAA was also standardized to Cho.RESULTS: Val/Met (n=35) showed markedly greater age-related decline in left DLPFC NAA/Cr level than Val/Val (n=60); no differences in mean metabolite levels were observed between Val/Met and Val/Val. Val/Met demonstrated greater frequency of history of MDD and higher frequency of cannabis use disorder over 12 months prior to study.CONCLUSIONS: The greater age-related decline in left DLPFC NAA/Cr and the higher frequency of MDD history and Cannabis Use disorder in BDNF rs6265 Met carriers with AUD are novel and may have implications for non-invasive brain stimulation targeting the left DLFPC and other psychosocial interventions typically utilized in the treatment of AUD.

    View details for DOI 10.1016/j.drugalcdep.2023.109901

    View details for PubMedID 37146499

  • Brain tract structure predicts relapse to stimulant drug use. Proceedings of the National Academy of Sciences of the United States of America Tisdall, L., MacNiven, K. H., Padula, C. B., Leong, J. K., Knutson, B. 2022; 119 (26): e2116703119

    Abstract

    Diffusion tractography allows identification and measurement of structural tracts in the human brain previously associated with motivated behavior in animal models. Recent findings indicate that the structural properties of a tract connecting the midbrain to nucleus accumbens (NAcc) are associated with a diagnosis of stimulant use disorder (SUD), but not relapse. In this preregistered study, we used diffusion tractography in a sample of patients treated for SUD (n = 60) to determine whether qualities of tracts projecting from medial prefrontal, anterior insular, and amygdalar cortices to NAcc might instead foreshadow relapse. As predicted, reduced diffusion metrics of a tract projecting from the right anterior insula to the NAcc were associated with subsequent relapse to stimulant use, but not with previous diagnosis. These findings highlight a structural target for predicting relapse to stimulant use and further suggest that distinct connections to the NAcc may confer risk for relapse versus diagnosis.

    View details for DOI 10.1073/pnas.2116703119

    View details for PubMedID 35727973

  • Active Cigarette Smoking Is Associated With Increased Age-Related Decline on Measures of Visuospatial Learning and Memory and Executive Function in Alcohol Use Disorder. Alcohol and alcoholism (Oxford, Oxfordshire) Padula, C. B., Durazzo, T. C. 2022

    Abstract

    AIMS: The goal of this study was to determine if active cigarette smoking in Veterans with alcohol use disorder (AUD) was associated with greater age-related neurocognitive decline.METHODS: Veterans with AUD, in residential treatment (n=125; 47±14years of age, min=24, max=76, 29±26days of abstinence), completed measures of executive functions, learning and memory, processing speed and working memory. Actively smoking AUD (AsAUD, n=47) were active daily cigarette smokers; former smoking AUD (FsAUD, n=45) were predominately daily smokers prior to study but did not smoke at the time of study; non-smoking AUD (NsAUD, n=33) never used cigarettes or smoked 'only a few times' during lifetime.RESULTS: AsAUD demonstrated greater age-related decline on measures of visuospatial learning and memory, and response inhibition/cognitive flexibility, primarily relative to NsAUD; there were no age-related differences between FsAUD and NsAUD on any measure. There were few significant mean differences between groups across the 15 neurocognitive measures. In AsAUD, higher scores on indices of smoking severity were associated with poorer performance on measures of auditory-verbal learning and memory, response inhibition, set-shifting and working memory. In FsAUD, longer smoking cessation duration was related to lower PTSD, anxiety and depressive symptomatology.CONCLUSIONS: Active smoking was associated with accelerated age-related decline on cognitive functions implicated in response to common evidence-based AUD interventions. Results suggest that smoking history contributes to the considerable heterogeneity observed in neurocognitive function in early AUD recovery, and reinforce the clinical movement to offer smoking cessation resources concurrent with treatment for AUD.

    View details for DOI 10.1093/alcalc/agac022

    View details for PubMedID 35552594

  • Transdiagnostic Versus Traditional Diagnostic Approaches to Psychiatric Symptoms in Alcohol Use Disorder: Associations With Emotion Regulation and Salience Network Function Tenekedjieva, L., Goldstein-Piekarski, A. N., Madore, M. R., Kaur, M., Coffigny, M., Padula, C. B. ELSEVIER SCIENCE INC. 2022: S104
  • 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

  • The Role of Neural Reward Expectancy and Valuation in Readiness to Change Among Treatment Seeking Veterans With Alcohol Use Disorder (AUD) Hagerty, S. L., Durazzo, T. C., Williams, L. M., Padula, C. B. ELSEVIER SCIENCE INC. 2021: S342
  • Dimensions of Craving Interact with COMT Genotype to Predict Relapse in Individuals with Alcohol Use Disorder Six Months after Treatment. Brain sciences Padula, C. B., Hansen, A., Hughes, R. L., McNerney, M. W. 2021; 11 (1)

    Abstract

    (1) Background: Alcohol use disorder (AUD) is associated with poor medical, psychological, and psychosocial outcomes and approximately 60% of individuals with AUD relapse six months after treatment. Craving is a core aspect of AUD and associated with high risk of relapse. One promising avenue to improve outcomes may be in understanding the relationship between COMT genotype, craving, and treatment outcomes. (2) Methods: To this end, we assessed craving, recent drinking history, and impulsivity in 70 individuals with AUD undergoing a standard course of treatment at a regional Veteran Affairs (VA) medical center. Saliva samples were collected to determine COMT genotype. In this prospective observational study, participants were followed for six months to determine who went on to relapse after treatment. (3) Results: Results revealed a significant interaction between craving and catechol-O-methyltransferse (COMT) genotype in predicting relapse. Post hoc exploratory analyses indicated that Met/Met homozygotes reported the highest levels of craving, and craving was associated with recent drinking history. Among Val/Val homozygotes, who had higher rates of relapse, craving was associated with impulsivity. (4) Conclusions: These associations highlight that specific profiles of psychological and biological factors may be important in understanding which individuals are at highest risk of relapse following treatment. Future studies that build on these findings are warranted.

    View details for DOI 10.3390/brainsci11010062

    View details for PubMedID 33419001

  • Heart Rate, Brain Imaging Biomarkers and Cognitive Impairment in Older (>= 63 years) Women AMERICAN JOURNAL OF CARDIOLOGY Haring, B., Liu, J., Rapp, S. R., Shimbo, D., Padula, C. B., Mozhui, K., Li, W., Espeland, M., Wassertheil-Smoller, S. 2020; 129: 102-108

    Abstract

    Evidence on the relations between heart rate, brain morphology, and cognition is limited. We examined the associations of resting heart rate (RHR), visit-to-visit heart rate variation (VVHRV), brain volumes and cognitive impairment. The study sample consisted of postmenopausal women enrolled in the Women's Health Initiative Memory Study and its ancillary MRI sub-studies (WHIMS-MRI 1 and WHIMS-MRI 2) without a history of cardiovascular disease, including 493 with one and 299 women with 2 brain magnetic resonance imaging (MRI) scans. HR readings were acquired annually starting from baseline visit (1996-1998). RHR was calculated as the mean and VVHRV as standard deviation of all available HR readings. Brain MRI scans were performed between 2005 and 2006 (WHIMS-MRI 1), and approximately 5 years later (WHIMS-MRI 2). Cognitive impairment was defined as incident mild cognitive impairment or probable dementia until December 30, 2017. An elevated RHR was associated with greater brain lesion volumes at the first MRI exam (7.86 cm3 [6.48, 9.24] vs 4.78 cm3 [3.39, 6.17], p-value <0.0001) and with significant increases in lesion volumes between brain MRI exams (6.20 cm3 [4.81, 7.59] vs 4.28 cm3 [2.84, 5.73], p-value = 0.0168). Larger ischemic lesion volumes were associated with a higher risk for cognitive impairment (Hazard Ratio [95% confidence interval], 2.02 [1.18, 3.47], p-value = 0.0109). Neither RHR nor VVHRV were related to cognitive impairment. In sensitivity analyses, we additionally included women with a history of cardiovascular disease to the study sample. The main results were consistent to those without a history of cardiovascular disease. In conclusion, these findings show an association between elevated RHR and ischemic brain lesions, probably due to underlying subclinical disease processes.

    View details for DOI 10.1016/j.amjcard.2020.05.030

    View details for Web of Science ID 000553464500016

    View details for PubMedID 32576368

  • Predicting relapse after alcohol use disorder treatment in a high-risk cohort: The roles of anhedonia and smoking. Journal of psychiatric research Nguyen, L., Durazzo, T. C., Dwyer, C. L., Rauch, A. A., Humphreys, K., Williams, L. M., Padula, C. B. 2020; 126: 1–7

    Abstract

    On average, two-thirds of individuals treated for alcohol use disorder (AUD) relapse within six months. There is a critical need to identify modifiable risk factors associated with relapse that can be addressed during AUD treatment. Candidate factors include mood disorders and cigarette smoking, which frequently co-occur with AUD. We predicted that co-occurrence of mood disorders, cigarette smoking, and other modifiable conditions will predict relapse within six months of AUD treatment. Ninety-five Veterans, 23-91 years old, completed assessments of multiple characteristics including demographic information, co-occurring psychiatric disorders, and medical conditions during residential treatment for AUD. Participants' alcohol consumption was monitored over six months after participation. Logistic regression was used to determine if, mood disorders, cigarette smoking status, alcohol consumption, educational level, and comorbid general medical conditions are associated with relapse after AUD treatment. Sixty-nine percent of Veterans (n=66) relapsed within six months of study while 31% remained abstinent (n=29). While education, comorbid general medical conditions, and mood disorder diagnoses were not predictors of relapse, Veterans with greater symptoms of anhedonia, active smokers, and fewer days of abstinence prior to treatment showed significantly greater odds for relapse within six months. Anhedonia and cigarette smoking are modifiable risk factors, and effective treatment of underlying anhedonic symptoms and implementation of smoking cessation concurrent with AUD-focused interventions may decrease risk of relapse.

    View details for DOI 10.1016/j.jpsychires.2020.04.003

    View details for PubMedID 32403028

  • NEUROPHYSIOLOGICAL CORRELATES OF REWARD ANTICIPATION AND ANHEDONIA IN VETERANS WITH ALCOHOL USE DISORDER Rauch, A., Williams, L., Dwyer, C., Linh-Chi Nguyen, Padula, C. WILEY. 2019: S119
  • Brain activation to cannabis- and alcohol-related words in alcohol use disorder. Psychiatry research. Neuroimaging Müller-Oehring, E. M., Berre, A. L., Serventi, M. n., Kalon, E. n., Haas, A. L., Padula, C. B., Schulte, T. n. 2019; 294: 111005

    Abstract

    Cannabis abuse commonly co-occurs with alcohol use disorder (AUD). With increased acceptance and accessibility to cannabis in the US, it is imperative to understand the psychological and neural mechanisms of concurrent alcohol and cannabis use. We hypothesized that neural alcohol-cue conditioning may extent to other drug-related stimuli, such as cannabis, and underwrite the loss of control over reward-driven behavior. Task-activated fMRI examined the neural correlates of alcohol- and cannabis-related word cues in 21 abstinent AUD and 18 control subjects. Relative to controls, AUD showed behavioral attentional biases and frontal hypoactivation to both alcohol- and cannabis-related words. This cue-elicited prefrontal hypoactivation was related to higher lifetime alcohol consumption (pcorrected < 0.02) and modulated by past cannabis use histories (p ≦ 0.001). In particular, frontal hypoactivation to both alcohol and cannabis cues was pronounced in AUD without prior cannabis exposure. Overall, frontal control mechanisms in abstinent AUD were not sufficiently engaged to override automatic alcohol and cannabis-related intrusions, enhancing the risk for relapse and potentially for alcohol and cannabis co-use with the increased social acceptance and accessibility in the US.

    View details for DOI 10.1016/j.pscychresns.2019.111005

    View details for PubMedID 31715379

  • Mean Heart Rate and Brain Morphology in Elderly Women Without a History of Cardiovascular Disease Haring, B., Liu, J., Shimbo, D., Padula, C. B., Li, W., Mozhui, K., Rapp, S., Espeland, M., Wassertheil-Smoller, S. LIPPINCOTT WILLIAMS & WILKINS. 2019
  • Association of Neural Responses to Drug Cues With Subsequent Relapse to Stimulant Use JAMA Netw Open MacNiven, K. H., Jensen, E. L., Borg, N., Padula, C. B., Humphreys, K., Knutson, B. 2018
  • Blunted amygdala functional connectivity during a stress task in alcohol dependent individuals: A pilot study. Neurobiology of stress Wade, N. E., Padula, C. B., Anthenelli, R. M., Nelson, E., Eliassen, J., Lisdahl, K. M. 2017; 7: 74-79

    Abstract

    Scant research has been conducted on neural mechanisms underlying stress processing in individuals with alcohol dependence (AD). We examined neural substrates of stress in AD individuals compared with controls using an fMRI task previously shown to induce stress, assessing amygdala functional connectivity to medial prefrontal cortex (mPFC).For this novel pilot study, 10 abstinent AD individuals and 11 controls completed a modified Trier stress task while undergoing fMRI acquisition. The amygdala was used as a seed region for whole-brain seed-based functional connectivity analysis.After controlling for family-wise error (p = 0.05), there was significantly decreased left and right amygdala connectivity with frontal (specifically mPFC), temporal, parietal, and cerebellar regions. Subjective stress, but not craving, increased from pre-to post-task.This study demonstrated decreased connectivity between the amygdala and regions important for stress and emotional processing in long-term abstinent individuals with AD. These results suggest aberrant stress processing in individuals with AD even after lengthy periods of abstinence.

    View details for DOI 10.1016/j.ynstr.2017.05.004

    View details for PubMedID 28626785

    View details for PubMedCentralID PMC5466595

  • The association between an inflammatory diet and global cognitive function and incident dementia in older women: The Women's Health Initiative Memory Study ALZHEIMERS & DEMENTIA Hayden, K. M., Beavers, D. P., Steck, S. E., Hebert, J. R., Tabung, F. K., Shivappa, N., Casanova, R., Manson, J. E., Padula, C. B., Salmoirago-Blotcher, E., Snetselaar, L. G., Zaslavsky, O., Rapp, S. R. 2017; 13 (11): 1187-1196

    Abstract

    The Mediterranean and Dietary Approaches to Stop Hypertension diets have been associated with lower dementia risk. We evaluated dietary inflammatory potential in relation to mild cognitive impairment (MCI)/dementia risk.Baseline food frequency questionnaires from n = 7085 women (aged 65-79 years) were used to calculate Dietary Inflammatory Index (DII) scores that were categorized into four groups. Cognitive function was evaluated annually, and MCI and all-cause dementia cases were adjudicated centrally. Mixed effect models evaluated cognitive decline on over time; Cox models evaluated the risk of MCI or dementia across DII groups.Over an average of 9.7 years, there were 1081 incident cases of cognitive impairment. Higher DII scores were associated with greater cognitive decline and earlier onset of cognitive impairment. Adjusted hazard ratios (HRs) comparing lower (anti-inflammatory; group 1 referent) DII scores to the higher scores were group 2-HR: 1.01 (0.86-1.20); group 3-HR: 0.99 (0.82-1.18); and group 4-HR: 1.27 (1.06-1.52).Diets with the highest pro-inflammatory potential were associated with higher risk of MCI or dementia.

    View details for DOI 10.1016/j.jalz.2017.04.004

    View details for Web of Science ID 000414349400001

    View details for PubMedID 28531379

    View details for PubMedCentralID PMC5909961

  • Cannabis use patterns and motives: A comparison of younger, middle-aged, and older medical cannabis dispensary patients ADDICTIVE BEHAVIORS Haug, N. A., Padula, C. B., Sottile, J. E., Vandrey, R., Heinz, A. J., Bonn-Miller, M. O. 2017; 72: 14-20

    Abstract

    Medical cannabis is increasingly being used for a variety of health conditions as more states implement legislation permitting medical use of cannabis. Little is known about medical cannabis use patterns and motives among adults across the lifespan.The present study examined data collected at a medical cannabis dispensary in San Francisco, California. Participants included 217 medical cannabis patients who were grouped into age-defined cohorts (younger: 18-30, middle-aged: 31-50, and older: 51-72). The age groups were compared on several measures of cannabis use, motives and medical conditions using one-way ANOVAs, chi-square tests and linear regression analyses.All three age groups had similar frequency of cannabis use over the past month; however, the quantity of cannabis used and rates of problematic cannabis use were higher among younger users relative to middle-aged and older adults. The association between age and problematic cannabis use was moderated by age of regular use initiation such that earlier age of regular cannabis use onset was associated with more problematic use in the younger users, but not among older users. Middle-aged adults were more likely to report using medical cannabis for insomnia, while older adults were more likely to use medical cannabis for chronic medical problems such as cancer, glaucoma and HIV/AIDS. Younger participants reported cannabis use when bored at a greater rate than middle-aged and older adults.Findings suggest that there is an age-related risk for problematic cannabis use among medical cannabis users, such that younger users should be monitored for cannabis use patterns that may lead to deleterious consequences.

    View details for DOI 10.1016/j.addbeh.2017.03.006

    View details for Web of Science ID 000403859300003

    View details for PubMedID 28340421

    View details for PubMedCentralID PMC5492936

  • Utilizing a transdiagnostic neuroscience-informed approach to differentiate the components of a complex clinical presentation: A case report. Personalized medicine in psychiatry Vanden Bussche, A. B., Haug, N. A., Ball, T. M., Padula, C. B., Goldstein-Pierarski, A. N., Williams, L. M. 2017; 3: 30-37

    Abstract

    Recent research recognizes considerable overlap in the clinical presentation of psychiatric disorders such as Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder and Social Anxiety Disorder. The diagnostic approach collects symptoms to reflect a single underlying psychopathological process. The Research Domain Criteria (RDoC) emphasizes psychopathology as arising from combinations of abnormalities in core underlying constructs that can be measured at many levels of analysis, from biological to behavioral. Patients who present with clinical heterogeneity may benefit from transdiagnostic case conceptualization that integrates detailed symptom information across multiple measurements spanning multiple domains of functioning based in the RDoC framework.We report on one case that was included in a research study focused on advancing knowledge towards a transdiagnostic, brain-based model of anxiety and depression. The 20-year-old male patient presented at a community mental health clinic for inattention, low mood, sleep problems and anxious symptoms. The patient also presented with primary problems in negative valence systems (anxiety, avoidance, and bias towards negative information), cognitive systems (fluctuating cognitive ability over time, poor concentration and ability to focus), and social processing systems (deficits in social communication skills). Conceptualizing this case through a transdiagnostic lens augmented the patient's treatment plan by including a more integrative approach. Treatment included social skills training, progressive relaxation exercises, and basic psychoeducation in emotional expression and independent living skills.This case illustrates the utility of a transdiagnostic approach, particularly when a traditional diagnostic model generates conflicting evidence and/or multiple comorbidities. RDoC provides a framework for integrating abnormalities across multiple dimensions. Furthermore, it lays the foundation for future integration of brain-behavior relationships into case conceptualization and personalized treatment approaches.

    View details for DOI 10.1016/j.pmip.2017.04.001

    View details for PubMedID 36968341

    View details for PubMedCentralID PMC10038350

  • Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in Two Age Groups JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Espeland, M. A., Rapp, S. R., Manson, J. E., Goveas, J. S., Shumaker, S. A., Hayden, K. M., Weitlauf, J. C., Gaussoin, S. A., Baker, L. D., Padula, C. B., Hou, L., Resnick, S. M., WHIMSY WHIMS-ECHO Study Grp 2017; 72 (6): 838–45

    Abstract

    Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age.Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos.Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p < .05. These decrements were relatively stable over time. Findings did not vary depending on the hormone therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase.CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years.

    View details for PubMedID 27506836

  • Longitudinal Cognitive Trajectories of Women Veterans from the Women's Health Initiative Memory Study. Gerontologist Padula, C. B., Weitlauf, J. C., Rosen, A. C., Reiber, G., Cochrane, B. B., Naughton, M. J., Li, W., Rissling, M., Yaffe, K., Hunt, J. R., Stefanick, M. L., Goldstein, M. K., Espeland, M. A. 2016; 56 (1): 115-125

    Abstract

    A comparison of longitudinal global cognitive functioning in women Veteran and non-Veteran participants in the Women's Health Initiative (WHI).We studied 7,330 women aged 65-79 at baseline who participated in the WHI Hormone Therapy Trial and its ancillary Memory Study (WHIMS). Global cognitive functioning (Modified Mini-Mental State Examination [3MSE]) in Veterans (n = 279) and non-Veterans (n = 7,051) was compared at baseline and annually for 8 years using generalized linear modeling methods.Compared with non-Veterans, Veteran women were older, more likely to be Caucasian, unmarried, and had higher rates of educational and occupational attainment. Results of unadjusted baseline analyses suggest 3MSE scores were similar between groups. Longitudinal analyses, adjusted for age, education, ethnicity, and WHI trial assignment revealed differences in the rate of cognitive decline between groups over time, such that scores decreased more in Veterans relative to non-Veterans. This relative difference was more pronounced among Veterans who were older, had higher educational/occupational attainment and greater baseline prevalence of cardiovascular risk factors (e.g., smoking) and cardiovascular disease (e.g., angina, stroke).Veteran status was associated with higher prevalence of protective factors that may have helped initially preserve cognitive functioning. However, findings ultimately revealed more pronounced cognitive decline among Veteran relative to non-Veteran participants, likely suggesting the presence of risks that may impact neuropathology and the effects of which were initially masked by Veterans' greater cognitive reserve.

    View details for DOI 10.1093/geront/gnv663

    View details for PubMedID 26615021

  • Alcohol Consumption Levels and All-Cause Mortality Among Women Veterans and Non-Veterans Enrolled in the Women's Health Initiative. Gerontologist Simpson, T. L., Rillamas-Sun, E., Lehavot, K., Timko, C., Rubin, A., Cucciare, M. A., Williams, E. C., Padula, C. B., Hunt, J. R., Hoggatt, K. J. 2016; 56: S138-49

    Abstract

    To address research gaps regarding women Veterans' alcohol consumption and mortality risk as compared to non-Veterans, the current study evaluated whether alcohol consumption amounts differed between women Veterans and non-Veterans, whether Veterans and non-Veterans within alcohol consumption groups differed on all-cause mortality, and whether Veteran status modified the association between alcohol consumption and all-cause mortality.Six alcohol consumption groups were created using baseline data from the Women's Health Initiative Program (N = 145,521): lifelong abstainers, former drinkers, less than 1 drink/week (infrequent drinkers), 1-7 drinks/week (moderate drinkers), 8-14 drinks/week (moderately heavy drinkers), and 15 or more drinks/week (heavy drinkers). The proportions of Veteran and non-Veteran women within each alcohol consumption category were compared. Mortality rates within each alcohol consumption category were compared by Veteran status. Cox proportional hazard models, including a multiplicative interaction term for Veteran status, were fit to estimate adjusted mortality hazard (rate) ratios for each alcohol consumption category relative to a reference group of either lifelong abstainers or moderate drinkers.Women Veterans were less likely to be lifelong abstainers than non-Veterans. Women Veterans who were former or moderate drinkers had higher age-adjusted mortality rates than did non-Veterans within these alcohol consumption categories. In the fully adjusted multivariate models, Veteran status did not modify the association between alcohol consumption category and mortality with either lifelong abstainers or moderate drinkers as referents.The results suggest that healthcare providers may counsel Veteran and non-Veteran women in similar ways regarding safe and less safe levels of alcohol consumption.

    View details for DOI 10.1093/geront/gnv667

    View details for PubMedID 26768387

  • Impact of Type 2 Diabetes and Postmenopausal Hormone Therapy on Incidence of Cognitive Impairment in Older Women. Diabetes care Espeland, M. A., Brinton, R. D., Hugenschmidt, C., Manson, J. E., Craft, S., Yaffe, K., Weitlauf, J., Vaughan, L., Johnson, K. C., Padula, C. B., Jackson, R. D., Resnick, S. M. 2015; 38 (12): 2316-2324

    Abstract

    In older women, higher levels of estrogen may exacerbate the increased risk for cognitive impairment conveyed by diabetes. We examined whether the effect of postmenopausal hormone therapy (HT) on cognitive impairment incidence differs depending on type 2 diabetes.The Women's Health Initiative (WHI) randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without [i.e., unopposed] 2.5 mg/day medroxyprogesterone acetate) or matching placebo for an average of 4.7-5.9 years. A total of 7,233 women, aged 65-80 years, were classified according to type 2 diabetes status and followed for probable dementia and cognitive impairment (mild cognitive impairment or dementia).Through a maximum of 18 years of follow-up, women with diabetes had increased risk of probable dementia (hazard ratio [HR] 1.54 [95% CI 1.16-2.06]) and cognitive impairment (HR 1.83 [1.50-2.23]). The combination of diabetes and random assignment to HT increased their risk of dementia (HR 2.12 [1.47-3.06]) and cognitive impairment (HR 2.20 [1.70-2.87]) compared with women without these conditions, interaction P = 0.09 and P = 0.08. These interactions appeared to be limited to women assigned to unopposed conjugated equine estrogens.These analyses provide additional support to a prior report that higher levels of estrogen may exacerbate risks that type 2 diabetes poses for cognitive function in older women. The role estrogen plays in suppressing non-glucose-based energy sources in the brain may explain this interaction.

    View details for DOI 10.2337/dc15-1385

    View details for PubMedID 26486190

    View details for PubMedCentralID PMC4657616

  • Craving is associated with amygdala volumes in adolescent marijuana users during abstinence. American journal of drug and alcohol abuse Padula, C. B., McQueeny, T., Lisdahl, K. M., Price, J. S., Tapert, S. F. 2015; 41 (2): 127-132

    Abstract

    Abstract Background: Amygdala volume abnormalities have been reported in relation to craving in substance-dependent adults, but it remains unclear if these effects are seen in adolescent marijuana (MJ) users, particularly following abstinence.The aim of this study was to examine the relationship between amygdala volume and craving during 28 days of abstinence in adolescent MJ users.MJ-using adolescents (n = 22) aged 16-19 were recruited as part of a larger study on brain function in teen drug users. Craving measures were collected twice per week throughout a 28-day abstinence period. High-resolution anatomical magnetic resonance imaging data were collected at the end of the 28 days of confirmed abstinence. Left and right amygdala volumes were traced by hand (ICC > 0.86). Composite scores for self-reported craving and withdrawal symptoms throughout the 28-day abstinence period were calculated to provide four composite measures of total craving, mood, sleep, and somatic complaints.RESULTS revealed that greater craving during abstinence was significantly associated with smaller left and right amygdala volumes, after controlling for age and gender. Other measures of withdrawal, including mood, somatic complaints and sleep problems, were not related to amygdala morphometry.These results are consistent with previous findings in adult alcohol- and cocaine-dependent individuals, who demonstrated a relationship between reduced amygdala volumes and increased craving. Future studies are needed to determine if these brain-behavior relationships are attributable to MJ use or predate the onset of substance use.

    View details for DOI 10.3109/00952990.2014.966198

    View details for PubMedID 25668330

  • Gender effects in alcohol dependence: an FMRI pilot study examining affective processing. Alcoholism, clinical and experimental research Padula, C. B., Anthenelli, R. M., Eliassen, J. C., Nelson, E., Lisdahl, K. M. 2015; 39 (2): 272-281

    Abstract

    Alcohol dependence (AD) has global effects on brain structure and function, including frontolimbic regions regulating affective processing. Preliminary evidence suggests alcohol blunts limbic response to negative affective stimuli and increases activation to positive affective stimuli. Subtle gender differences are also evident during affective processing.Fourteen abstinent AD individuals (8 F, 6 M) and 14 healthy controls (9 F, 5 M), ages 23 to 60, were included in this facial affective processing functional magnetic resonance imaging pilot study. Whole-brain linear regression analyses were performed, and follow-up analyses examined whether AD status significantly predicted depressive symptoms and/or coping.Fearful Condition-The AD group demonstrated reduced activation in the right medial frontal gyrus, compared with controls. Gender moderated the effects of AD in bilateral inferior frontal gyri. Happy Condition-AD individuals had increased activation in the right thalamus. Gender moderated the effects of AD in the left caudate, right middle frontal gyrus, left paracentral lobule, and right lingual gyrus. Interactive AD and gender effects for fearful and happy faces were such that AD men activated more than control men, but AD women activated less than control women. Enhanced coping was associated with greater activation in right medial frontal gyrus during fearful condition in AD individuals.Abnormal affective processing in AD may be a marker of alcoholism risk or a consequence of chronic alcoholism. Subtle gender differences were observed, and gender moderated the effects of AD on neural substrates of affective processing. AD individuals with enhanced coping had brain activation patterns more similar to controls. Results help elucidate the effects of alcohol, gender, and their interaction on affective processing.

    View details for DOI 10.1111/acer.12626

    View details for PubMedID 25684049

  • Cognition and Competency Restoration: Using the RBANS to Predict Length of Stay for Patients Deemed Incompetent to Stand Trial CLINICAL NEUROPSYCHOLOGIST Ross, P. T., Padula, C. B., Nitch, S. R., Kinney, D. I. 2015; 29 (1): 150-165

    Abstract

    Intact cognition is a foundational component of one's ability to be competent to stand trial. Given the cost of assessing and treating incompetence, it is recommended that clinicians develop efficient methods to identify individuals who are most likely to require intensive competence-related treatment interventions. This study sought to ascertain whether a brief cognitive screening instrument, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), could predict the length of stay required to restore trial competency among 288 forensic psychiatric inpatients undergoing competency restoration treatment. Results indicated that incompetent defendants who were older or demonstrated poorer overall RBANS performance required longer hospitalizations to be deemed restored to trial competence. Interestingly, incompetent defendants scoring in the 51-60 range on the RBANS Total Scale Index were almost three times more likely to require hospitalization beyond the average length of stay. Findings support the use of the RBANS to identify individuals early in the treatment process who may require and benefit from intensive restoration treatment.

    View details for DOI 10.1080/13854046.2015.1005678

    View details for Web of Science ID 000350299000011

    View details for PubMedID 25650794