Bio


Dr. Kathleen Poston is Associate Professor of Neurology & Neurological Sciences and (by courtesy) Neurosurgery at Stanford University Medical Center. She received her Bachelor's of Science in Bioengineering at the University of Pennsylvania, her Master's Degree in Biomedical Engineering and her MD at Vanderbilt University where she received the Medical Student Prize for Excellence in Neurology. She completed her Neurology residency training at UCSF, where she was Chief Resident. She also completed a fellowship in clinical Movement Disorders under the mentorship of Dr. Stanley Fahn at Columbia University and post-doctoral research training in Functional Neuroimaging with Dr. David Eidelberg at the Feinstein Institute.

Dr. Poston's research focuses on the development of novel neuroimaging biomarkers to improve diagnostic accuracy and monitor the efficacy of investigational treatments for Parkinson's Disease and other movement disorders. Her current studies focus on cognitive and memory problems in people with Parkinson’s disease. She has been awarded grant funding by the NIH and the Michael J. Fox Foundation for Parkinson’s disease research. She is co-investigator for the Stanford Alzheimer’s disease Center (ADRC), which is funded by the National Institute for Aging and will focus on early cognitive problems in both Parkinson’s disease and Alzheimer’s disease. She is also co-investigator for the NINDS funded Morris K. Udall Center of Excellence for Parkinson’s disease Research.

Clinical Focus


  • Neurology
  • Parkinson Disease
  • Dementia with Lewy Bodies
  • Parkinsonian Disorders
  • Multiple System Atrophy
  • Palsy, Progressive Supranuclear
  • Corticobasal Syndrome

Academic Appointments


Honors & Awards


  • Lysia Forno Award for Teaching Excellence, Stanford University (2009-2010)

Professional Education


  • Residency:Univ of California San FranciscoCA
  • Internship:Univ of California San FranciscoCA
  • Fellowship:Columbia University Medical CenterNY
  • Medical Education:Vanderbilt University School of Medicine (2002) TN
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (2007)
  • Post-Doc, Feinstein Institute, Functional Neuroimaging (2009)
  • BSE, University of Pennsylvania, Bioengineering
  • MS, Vanderbilt University, Bioengineering (1998)

Current Research and Scholarly Interests


Dr. Poston’s research interests include the development, validation and application of functional and structural neuroimaging as biomarkers for the diagnosis and treatment of movement disorders. Specifically, her research focuses on using FDG PET and fMRI to understand abnormal brain networks that lead to both motor and cognitive dysfunction in patients with parkinsonism. She is also interested in the development of novel imaging analysis techniques for establishing diagnosis and monitoring disease progression in early parkinsonian disorders, such as Parkinson’s disease, multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Such techniques can be used in the development and testing of novel therapeutic interventions, such as gene transfer therapy in Parkinson’s disease.

2019-20 Courses


Stanford Advisees


Graduate and Fellowship Programs


All Publications


  • Clinical and dopamine transporter imaging characteristics of non-manifest LRRK2 and GBA mutation carriers in the Parkinson's Progression Markers Initiative (PPMI): a cross-sectional study. The Lancet. Neurology Simuni, T., Uribe, L., Cho, H. R., Caspell-Garcia, C., Coffey, C. S., Siderowf, A., Trojanowski, J. Q., Shaw, L. M., Seibyl, J., Singleton, A., Toga, A. W., Galasko, D., Foroud, T., Tosun, D., Poston, K., Weintraub, D., Mollenhauer, B., Tanner, C. M., Kieburtz, K., Chahine, L. M., Reimer, A., Hutten, S. J., Bressman, S., Marek, K., PPMI Investigators, Arnedo, V., Clark, A., Fraiser, M., Kopil, C., Chowdhury, S., Sherer, T., Daegele, N., Casaceli, C., Dorsey, R., Wilson, R., Mahes, S., Salerno, C., Crawford, K., Casalin, P., Malferrari, G., Weisz, M. G., Orr-Urtreger, A., Montine, T., Baglieri, C., Christini, A., Russell, D., Dahodwala, N., Giladi, N., Factor, S., Hogarth, P., Standaert, D., Hauser, R., Jankovic, J., Saint-Hilaire, M., Richard, I., Shprecher, D., Fernandez, H., Brockmann, K., Rosenthal, L., Barone, P., Espay, A., Rowe, D., Marder, K., Santiago, A., Hu, S., Isaacson, S., Corvol, J., Ruiz Martinez, J., Tolosa, E., Tai, Y., Politis, M., Smejdir, D., Rees, L., Williams, K., Kausar, F., Williams, K., Richardson, W., Willeke, D., Peacock, S., Sommerfeld, B., Freed, A., Wakeman, K., Blair, C., Guthrie, S., Harrell, L., Hunter, C., Thomas, C., James, R., Zimmerman, G., Brown, V., Mule, J., Hilt, E., Ribb, K., Ainscough, S., Wethington, M., Ranola, M., Mejia Santana, H., Moreno, J., Raymond, D., Speketer, K., Carvajal, L., Carvalo, S., Croitoru, I., Garrido, A., Payne, L. M., Viswanth, V., Severt, L., Facheris, M., Soares, H., Mintun, M. A., Cedarbaum, J., Taylor, P., Biglan, K., Vandenbroucke, E., Haider Sheikh, Z., Bingol, B., Fischer, T., Sardi, P., Forrat, R., Reith, A., Egebjerg, J., Ahlberg Hillert, G., Saba, B., Min, C., Umek, R., Mather, J., De Santi, S., Post, A., Boess, F., Taylor, K., Grachev, I., Avbersek, A., Muglia, P., Merchant, K., Tauscher, J. 2019

    Abstract

    BACKGROUND: The Parkinson's Progression Markers Initiative (PPMI) is an ongoing observational, longitudinal cohort study of participants with Parkinson's disease, healthy controls, and carriers of the most common Parkinson's disease-related genetic mutations, which aims to define biomarkers of Parkinson's disease diagnosis and progression. All participants are assessed annually with a battery of motor and non-motor scales, 123-I Ioflupane dopamine transporter (DAT) imaging, and biological variables. We aimed to examine whether non-manifesting carriers of LRRK2 and GBA mutations have prodromal features of Parkinson's disease that correlate with reduced DAT binding.METHODS: This cross-sectional analysis is based on assessments done at enrolment in the subset of non-manifesting carriers of LRRK2 and GBA mutations enrolled into the PPMI study from 33 participating sites worldwide. The primary objective was to examine baseline clinical and DAT imaging characteristics in non-manifesting carriers with GBA and LRRK2 mutations compared with healthy controls. DAT deficit was defined as less than 65% of putamen striatal binding ratio expected for the individual's age. We used t tests, chi2 tests, and Fisher's exact tests to compare baseline demographics across groups. An inverse probability weighting method was applied to control for potential confounders such as age and sex. To account for multiple comparisons, we applied a family-wise error rate to each set of analyses. This study is registered with ClinicalTrials.gov, number NCT01141023.FINDINGS: Between Jan 1, 2014, and Jan 1, 2019, the study enrolled 208 LRRK2 (93% G2019S) and 184 GBA (96% N370S) non-manifesting carriers. Both groups were similar with respect to mean age, and about 60% were female. Of the 286 (73%) non-manifesting carriers that had DAT imaging results, 18 (11%) LRRK2 and four (3%) GBA non-manifesting carriers had a DAT deficit. Compared with healthy controls, both LRRK2 and GBA non-manifesting carriers had significantly increased mean scores on the Movement Disorders Society Unified Parkinson's Disease Rating Scale (total score 4·6 [SD 4·4] healthy controls vs 8·4 [7·3] LRRK2 vs 9·5 [9·2] GBA, p<0·0001 for both comparisons) and the Scale for Outcomes for PD - autonomic function (5·8 [3·7] vs 8·1 [5·9] and 8·4 [6·0], p<0·0001 for both comparisons). There was no difference in daytime sleepiness, anxiety, depression, impulsive-compulsive disorders, blood pressure, urate, and rapid eye movement (REM) behaviour disorder scores. Hyposmia was significantly more common only in LRRK2 non-manifesting carriers (69 [36%] of 194 healthy controls vs 114 [55%] of 208 LRRK2 non-manifesting carriers; p=0·0003). Finally, GBA but not LRRK2 non-manifesting carriers showed increased DAT striatal binding ratios compared with healthy controls in the caudate (healthy controls 2·98 [SD 0·63] vs GBA 3·26 [0·63]; p<0·0001), putamen (2·15 [0·56] vs 2·48 [0·52]; p<0·0001), and striatum (2·56 [0·57] vs 2·87 [0·55]; p<0·0001).INTERPRETATION: Our data show evidence of subtle motor and non-motor signs of Parkinson's disease in non-manifesting carriers compared with healthy controls that can precede DAT deficit. Longitudinal data will be essential to confirm these findings and define the trajectory and predictors for development of Parkinson's disease.FUNDING: Michael J Fox Foundation for Parkinson's Research.

    View details for DOI 10.1016/S1474-4422(19)30319-9

    View details for PubMedID 31678032

  • An increased rate of longitudinal cognitive decline is observed in Parkinson's disease patients with low CSF ASS42 and an APOE epsilon4 allele. Neurobiology of disease Shahid, M., Kim, J., Leaver, K., Hendershott, T., Zhu, D., Cholerton, B., Henderson, V. W., Tian, L., Poston, K. L. 2019

    Abstract

    OBJECTIVE: Low concentrations of cerebrospinal fluid (CSF) amyloid-beta (Abeta-42) are associated with increased risk of cognitive decline in Parkinson's disease (PD). We sought to determine whether APOE genotype modifies the rate of cognitive decline in PD patients with low CSF Abeta-42 compared to patients with normal levels.METHODS: The Parkinson's Progression Markers Initiative is a longitudinal, ongoing study of de novo PD participants, which includes APOE genotyping, CSF Abeta-42 determinations, and neuropsychological assessments. We used linear mixed effects models in three PD groups (PD participants with low CSF Abeta at baseline, PD participants with normal CSF Abeta, and both groups combined). Having at least one copy of the APOE ɛ4 allele, time, and the interaction of APOE ɛ4 and time were predictor variables for cognitive change, adjusting for age, gender and education.RESULTS: 423 de novo PD participants were followed up to 5 years with annual cognitive assessments. 103 participants had low baseline CSF Abeta-42 (39 APOE epsilon4+, 64 APOE epsilon4-). Compared to participants with normal CSF Abeta-42, those with low CSF Abeta-42 declined faster on most cognitive tests. Within the low CSF Abeta-42 group, APOE epsilon4+ participants had faster rates of decline on the Montreal Cognitive Assessment (primary outcome; 0.57 points annual decline, p = .005; 5-year standardized change of 1.2) and the Symbol Digit Modalities Test (1.4 points annual decline, p = .002; 5-year standardized change of 0.72).DISCUSSION: PD patients with low CSF Abeta-42 and APOE epsilon4+ showed a higher rate of cognitive decline early in the disease. Tests of global cognition (Montreal Cognitive Assessment) and processing speed (Symbol Digit Modalities Test) were the most sensitive to early cognitive decline. Results suggest that CSF Abeta-42 and APOE epsilon4 might interact to promote early cognitive changes in PD patients.

    View details for PubMedID 30826425

  • Dopamine-Related Dissociation of Cortical and Subcortical Brain Activations in Cognitively Unimpaired Parkinson's Disease Patients OFF and ON Medications. Neuropsychologia Kim, J., Zhang, K., Cai, W., YorkWilliams, S., I Ua Cruadhlaoich, M. A., Llanes, S., Menon, V., Poston, K. L. 2018

    Abstract

    BACKGROUND: Despite dopaminergic depletion that is severe enough to cause the motor symptoms of Parkinson's disease (PD), many patients remain cognitively unimpaired. Little is known about brain mechanisms underlying such preserved cognitive abilities and their alteration by dopaminergic medications.OBJECTIVES: We investigated brain activations underlying dopamine-related differences in cognitive function using a unique experimental design with PD patients off and on dopaminergic medications. We tested the dopamine overdose hypothesis, which posits that the excess of exogenous dopamine in the frontal cortical regions can impair cognition.METHODS: We used a two-choice forced response Choice Reaction Time (CRT) task to probe cognitive processes underlying response selection and execution. Functional magnetic resonance imaging data were acquired from 16 cognitively unimpaired (Level-II) PD participants and 15 well-matched healthy controls (HC). We compared task performance (i.e. reaction time and accuracy) and brain activation of PD participants off dopaminergic medications (PD_OFF) in comparison with HC, and PD_OFF participants with those on dopaminergic medications (PD_ON).RESULTS: PD_OFF and PD_ON groups did not differ from each other, or from the HC group, in reaction time or accuracy. Compared to HC, PD_OFF activated the bilateral putamen less, and this was compensated by higher activation of the anterior insula. No such differences were observed in the PD_ON group, compared to HC. Compared to both HC and PD_OFF, PD_ON participants showed dopamine-related hyperactivation in the frontal cortical regions and hypoactivation in the amygdala.CONCLUSION: Our data provide further evidence that PD_OFF and PD_ON participants engage different cortical and subcortical systems to achieve similar levels of cognitive performance as HC. Crucially, our findings demonstrate dopamine-related dissociation in brain activation between cortical and subcortical regions, and provide novel support for the dopamine overdose hypothesis.

    View details for PubMedID 30040957

  • Longitudinal Change of Clinical and Biological Measures in Early Parkinson's Disease: Parkinson's Progression Markers Initiative Cohort MOVEMENT DISORDERS Simuni, T., Siderowf, A., Lasch, S., Coffey, C. S., Caspell-Garcia, C., Jennings, D., Tanner, C. M., Trojanowski, J. Q., Shaw, L. M., Seibyl, J., Schuff, N., Singleton, A., Kieburtz, K., Toga, A. W., Mollenhauer, B., Galasko, D., Chahine, L. M., Weintraub, D., Foroud, T., Tosun, D., Poston, K., Arnedo, V., Frasier, M., Sherer, T., Chowdhury, S., Marek, K., Parkinson's Progression Marker Ini 2018; 33 (5): 771–82

    Abstract

    The objective of this study was to assess longitudinal change in clinical and dopamine transporter imaging outcomes in early, untreated PD.We describe 5-year longitudinal change of the MDS-UPDRS and other clinical measures using results from the Parkinson's Progression Markers Initiative, a longitudinal cohort study of early Parkinson's disease (PD) participants untreated at baseline. We also provide data on the longitudinal change in dopamine transporter 123-I Ioflupane striatal binding and correlation between the 2 measures.A total of 423 PD participants were recruited, and 358 remain in the study at year 5. Baseline MDS-UPDRS total score was 32.4 (standard deviation 13.1), and the average annual change (assessed medications OFF for the treated participants) was 7.45 (11.6), 3.11 (11.7), 4(11.9), 4.7 (11.1), and 1.74(11.9) for years 1, 2, 3, 4, and 5, respectively (P < .0001 for the change over time), with a steeper change in year 1. Dopaminergic therapy had a significant effect on the change of MDS-UPDRS. There was a significant longitudinal change in dopamine transporter binding in all striatal regions (P < .001). There was a significant but weak correlation between MDS-UPDRS and dopamine transporter binding at baseline and years 1, 2, and 4, but no correlation between the rate of change of the 2 variables.We present 5-year longitudinal data on the change of the MDS-UPDRS and other clinical and dopamine transporter imaging outcome measures in early PD. These data can be used for sample size estimates for interventional studies in the de novo PD population. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

    View details for PubMedID 29572948

    View details for PubMedCentralID PMC6001458

  • Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease. Parkinsonism & related disorders Cholerton, B., Johnson, C. O., Fish, B., Quinn, J. F., Chung, K. A., Peterson-Hiller, A. L., Rosenthal, L. S., Dawson, T. M., Albert, M. S., Hu, S., Mata, I. F., Leverenz, J. B., Poston, K. L., Montine, T. J., Zabetian, C. P., Edwards, K. L. 2018

    Abstract

    INTRODUCTION: Identification of factors associated with progression of cognitive symptoms in Parkinson's disease (PD) is important for treatment planning, clinical care, and design of future clinical trials. The current study sought to identify whether prediction of cognitive progression is aided by examining baseline cognitive features, and whether this differs according to stage of cognitive disease.METHODS: Participants with PD in the Pacific Udall Center Clinical Consortium who had longitudinal data available and were nondemented at baseline were included in the study (n = 418). Logistic and Cox regression models were utilized to examine the relationship between cognitive, demographic, and clinical variables with risk and time to progression from no cognitive impairment to mild cognitive impairment (PD-MCI) or dementia (PDD), and from PD-MCI to PDD.RESULTS: Processing speed (OR = 1.05, p = 0.009) and working memory (OR = 1.01, p = 0.03) were associated with conversion to PDD among those with PD-MCI at baseline, over and above demographic variables. Conversely, the primary predictive factor in the transition from no cognitive impairment to PD-MCI or PDD was male sex (OR = 4.47, p = 0.004), and males progressed more rapidly than females (p = 0.01). Further, among females with shorter disease duration, progression was slower than for their male counterparts, and poor baseline performance on semantic verbal fluency was associated with shorter time to cognitive impairment in females but not in males.CONCLUSIONS: This study provides evidence for sex differences in the progression to cognitive impairment in PD, while specific cognitive features become more important indicators of progression with impending conversion to PDD.

    View details for PubMedID 29478836

  • 7T MRI subthalamic nucleus atlas for use with 3T MRI JOURNAL OF MEDICAL IMAGING Milchenko, M., Norris, S. A., Poston, K., Campbell, M. C., Ushe, M., Perlmutter, J. S., Snyder, A. Z. 2018; 5 (1): 015002

    Abstract

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in most patients with Parkinson disease (PD), yet may produce untoward effects. Investigation of DBS effects requires accurate localization of the STN, which can be difficult to identify on magnetic resonance images collected with clinically available 3T scanners. The goal of this study is to develop a high-quality STN atlas that can be applied to standard 3T images. We created a high-definition STN atlas derived from seven older participants imaged at 7T. This atlas was nonlinearly registered to a standard template representing 56 patients with PD imaged at 3T. This process required development of methodology for nonlinear multimodal image registration. We demonstrate mm-scale STN localization accuracy by comparison of our 3T atlas with a publicly available 7T atlas. We also demonstrate less agreement with an earlier histological atlas. STN localization error in the 56 patients imaged at 3T was less than 1 mm on average. Our methodology enables accurate STN localization in individuals imaged at 3T. The STN atlas and underlying 3T average template in MNI space are freely available to the research community. The image registration methodology developed in the course of this work may be generally applicable to other datasets.

    View details for PubMedID 29340288

    View details for PubMedCentralID PMC5757662

  • Distinct alterations in Parkinson's medication-state and disease-state connectivity NEUROIMAGE-CLINICAL Ng, B., Varoquaux, G., Poline, J., Thirion, B., Greicius, M. D., Poston, K. L. 2017; 16: 575–85

    Abstract

    Altered brain connectivity has been described in people with Parkinson's disease and in response to dopaminergic medications. However, it is unclear whether dopaminergic medications primarily 'normalize' disease related connectivity changes or if they induce unique alterations in brain connectivity. Further, it is unclear how these disease- and medication-associated changes in brain connectivity relate differently to specific motor manifestations of disease, such as bradykinesia/rigidity and tremor. In this study, we applied a novel covariance projection approach in combination with a bootstrapped permutation test to resting state functional MRI data from 57 Parkinson's disease and 20 healthy control participants to determine the Parkinson's medication-state and disease-state connectivity changes associated with different motor manifestations of disease. First, we identified brain connections that best classified Parkinson's disease ON versus OFF dopamine and Parkinson's disease versus healthy controls, achieving 96.9 ± 5.9% and 72.7 ± 12.4% classification accuracy, respectively. Second, we investigated the connections that significantly contribute to the classifications. We found that the connections greater in Parkinson's disease OFF compared to ON dopamine are primarily between motor (cerebellum and putamen) and posterior cortical regions, such as the posterior cingulate cortex. By contrast, connections that are greater in ON compared to OFF dopamine are between the right and left medial prefrontal cortex. We also identified the connections that are greater in healthy control compared to Parkinson's disease and found the most significant connections are associated with primary motor regions, such as the striatum and the supplementary motor area. Notably, these are different connections than those identified in Parkinson's disease OFF compared to ON. Third, we determined which of the Parkinson's medication-state and disease-state connections are associated with the severity of different motor symptoms. We found two connections correlate with both bradykinesia/rigidity severity and tremor severity, whereas four connections correlate with only bradykinesia/rigidity severity, and five connections correlate with only tremor severity. Connections that correlate with only tremor severity are anchored by the cerebellum and the supplemental motor area, but only those connections that include the supplemental motor area predict dopaminergic improvement in tremor. Our results suggest that dopaminergic medications do not simply 'normalize' abnormal brain connectivity associated with Parkinson's disease, but rather dopamine drives distinct connectivity changes, only some of which are associated with improved motor symptoms. In addition, the dissociation between of connections related to severity of bradykinesia/rigidity versus tremor highlights the distinct abnormalities in brain circuitry underlying these specific motor symptoms.

    View details for PubMedID 28971008

  • Compensatory neural mechanisms in cognitively unimpaired Parkinson disease. Annals of neurology Poston, K. L., YorkWilliams, S., Zhang, K., Cai, W., Everling, D., Tayim, F. M., Llanes, S., Menon, V. 2016; 79 (3): 448-463

    Abstract

    Cognitive impairments in Parkinson's disease (PD) are thought to be caused in part by dopamine dysregulation. However, even when nigrostriatal dopamine neuron loss is severe enough to cause motor symptoms, many patients remain cognitively unimpaired. It is unclear what brain mechanisms allow these patients to remain cognitively unimpaired despite substantial dopamine dysregulation.31 cognitively unimpaired PD participants OFF dopaminergic-medications were scanned using fMRI while they performed a working memory task, along with 23 controls. We first compared the PD_OFF medication group with controls to determine whether PD participants engage compensatory frontostriatal mechanisms during working memory. We then studied the same PD participants ON dopaminergic-medications to determine whether these compensatory brain changes are altered with dopamine.Controls and PD showed working memory load-dependent activation in the bilateral putamen, anterior-dorsal insula, supplementary motor area, and anterior cingulate cortex. Compared to controls, PD_OFF showed compensatory hyper-activation of bilateral putamen and posterior insula, and machine learning algorithms identified robust differences in putamen activation patterns. Compared to PD_OFF, PD_ON showed reduced compensatory activation in the putamen. Loss of compensatory hyper-activation ON dopaminergic-medication correlated with slower performance on the working memory task and slower cognitive speed on the Symbol Digit Modality Test.Our results provide novel evidence that PD patients maintain normal cognitive performance through compensatory hyper-activation of the putamen. Dopaminergic-medication down-regulates this hyper-activation and the degree of down-regulation predicts behavior. Identifying cognitive compensatory mechanisms in PD is important for understanding how some patients maintain intact cognitive performance, despite nigrostriatal dopamine loss. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/ana.24585

    View details for PubMedID 26696272

  • Do CSF Biomarkers Predict Progression to Cognitive Impairment in Parkinson's disease patients? A Systematic Review. Neuropsychology review Leaver, K., Poston, K. L. 2015; 25 (4): 411-423

    Abstract

    Many patients with Parkinson's disease (PD) will develop cognitive impairment. Cross-sectional studies have shown that certain protein levels are altered in the cerebrospinal fluid (CSF) of PD patients with dementia and are thought to represent potential biomarkers of underlying pathogenesis. Recent studies suggest that CSF biomarker levels may be predictive of future risk of cognitive decline in non-demented PD patients. However, the strength of this evidence and difference between specific CSF biomarkers is not well delineated. We therefore performed a systematic review to assess if levels of specific CSF protein biomarkers are predictive of progression to cognitive impairment. Nine articles were identified that met inclusion criteria for the review. Findings from the review suggest a convergence of evidence that a low baseline Aβ42 in the CSF of non-demented PD patients predicts development of cognitive impairment over time. Conversely, there is limited evidence that CSF levels of tau, either total tau or phosphorylated tau, is a useful predictive biomarker. There are mixed results for other CSF biomarkers such as α-synuclein, Neurofilament light chain, and Heart fatty acid-binding protein. Overall the results of this review show that certain CSF biomarkers have better predictive ability to identify PD patients who are at risk for developing cognitive impairment. Given the interest in developing disease-modifying therapies, identifying this group will be important for clinical trials as initiation of therapy prior to the onset of cognitive decline is likely to be more efficacious.

    View details for DOI 10.1007/s11065-015-9307-8

    View details for PubMedID 26626621

    View details for PubMedCentralID PMC5152566

  • Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis LANCET NEUROLOGY Tang, C. C., Poston, K. L., Eckert, T., Feigin, A., Frucht, S., Gudesblatt, M., Dhawan, V., Lesser, M., Vonsattel, J., Fahn, S., Eidelberg, D. 2010; 9 (2): 149-158

    Abstract

    Idiopathic Parkinson's disease can present with symptoms similar to those of multiple system atrophy or progressive supranuclear palsy. We aimed to assess whether metabolic brain imaging combined with spatial covariance analysis could accurately discriminate patients with parkinsonism who had different underlying disorders.Between January, 1998, and December, 2006, patients from the New York area who had parkinsonian features but uncertain clinical diagnosis had fluorine-18-labelled-fluorodeoxyglucose-PET at The Feinstein Institute for Medical Research. We developed an automated image-based classification procedure to differentiate individual patients with idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. For each patient, the likelihood of having each of the three diseases was calculated by use of multiple disease-related patterns with logistic regression and leave-one-out cross-validation. Each patient was classified according to criteria defined by receiver-operating-characteristic analysis. After imaging, patients were assessed by blinded movement disorders specialists for a mean of 2.6 years before a final clinical diagnosis was made. The accuracy of the initial image-based classification was assessed by comparison with the final clinical diagnosis.167 patients were assessed. Image-based classification for idiopathic Parkinson's disease had 84% sensitivity, 97% specificity, 98% positive predictive value (PPV), and 82% negative predictive value (NPV). Imaging classifications were also accurate for multiple system atrophy (85% sensitivity, 96% specificity, 97% PPV, and 83% NPV) and progressive supranuclear palsy (88% sensitivity, 94% specificity, 91% PPV, and 92% NPV).Automated image-based classification has high specificity in distinguishing between parkinsonian disorders and could help in selecting treatment for early-stage patients and identifying participants for clinical trials.National Institutes of Health and General Clinical Research Center at The Feinstein Institute for Medical Research.

    View details for DOI 10.1016/S1474-4422(10)70002-8

    View details for Web of Science ID 000273922000012

    View details for PubMedID 20061183

  • Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson's disease. Neuroscience and biobehavioral reviews Sundaram, S., Hughes, R. L., Peterson, E., Muller-Oehring, E. M., Bronte-Stewart, H. M., Poston, K. L., Faerman, A., Bhowmick, C., Schulte, T. 2019

    Abstract

    Recent evidence has advanced our understanding of the function of sleep to include removal of neurotoxic protein aggregates via the glymphatic system. However, most research on the glymphatic system utilizes animal models, and the function of waste clearance processes in humans remains unclear. Understanding glymphatic function offers new insight into the development of neurodegenerative diseases that result from toxic protein inclusions, particularly those characterized by neuropathological sleep dysfunction, like Parkinson's disease (PD). In PD, we propose that glymphatic flow may be compromised due to the combined neurotoxic effects of alpha-synuclein protein aggregates and deteriorated dopaminergic neurons that are linked to altered REM sleep, circadian rhythms, and clock gene dysfunction. This review highlights the importance of understanding the functional role of glymphatic system disturbance in neurodegenerative disorders and the subsequent clinical and neuropathological effects on disease progression. Future research initiatives utilizing noninvasive brain imaging methods in human subjects with PD are warranted, as in vivo identification of functional biomarkers in glymphatic system functioning may improve clinical diagnosis and treatment of PD.

    View details for DOI 10.1016/j.neubiorev.2019.05.016

    View details for PubMedID 31132378

  • Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI) PARKINSONISM & RELATED DISORDERS Prakash, N., Caspell-Garcia, C., Coffey, C., Siderowf, A., Tanner, C. M., Kieburtz, K., Mollenhauer, B., Galasko, D., Merchant, K., Foroud, T., Chahine, L. M., Weintraub, D., Casaceli, C., Dorsey, R., Wilson, R., Herzog, M., Daegele, N., Arnedo, V., Frasier, M., Sherer, T., Marek, K., Frank, S., Jennings, D., Simuni, T., Marek, K., Siderowf, A., Seibyl, J., Coffey, C., Tanner, C., Tosun-Turgut, D., Simunir, T., Shaw, L., Trojanowski, J., Singleton, A., Kieburtz, K., Toga, A., Mollenhauer, B., Galasko, D., Poewe, W., Foroud, T., Poston, K., Sherer, T., Chowdhury, S., Frasier, M., Kopil, C., Arnedo, V., Marek, K., Daegele, N., Casaceli, C., Dorsey, R., Wilson, R., Mahes, S., Seibyl, J., Salerno, C., Coffey, C., Caspell-Garcia, C., Toga, A., Crawford, K., Foroud, T., Casalin, P., Malferrari, G., Weisz, M., Orr-Urtreger, A., Trojanowski, J., Shaw, L., Singleton, A., Foroud, T., Foroud, T., Montine, T., Russell, D., Tanner, C., Simuni, T., Dahodwala, N., Mollenhauer, B., Galasko, D., Poewe, W., Giladi, N., Factor, S., Hogarth, P., Standaert, D., Hauser, R., Jankovic, J., Saint-Hilaire, M., Richard, I., Shprecher, D., Fernandez, H., Brockmann, K., Rosenthal, L., Barone, P., Espay, A., Rowe, D., Marder, K., Santiago, A., Bressman, S., Hu, S., Isaacson, S., Corvol, J., Ruiz Martinez, J., Tolosa, E., Tai, Y., Politis, M., Smejdir, D., Rees, L., Williams, K., Kausar, F., Williams, K., Richardson, W., Willeke, D., Peacock, S., Heim, B., Mirelman, A., Sommerfeld, B., Freed, A., Wakeman, K., Blair, C., Guthrie, S., Harrell, L., Hunter, C., Thomas, C., James, R., Zimmerman, G., Brown, V., Mule, J., Hilt, E., Ribb, K., Ainscough, S., Wethington, M., Ranola, M., Santana, H., Moreno, J., Raymond, D., Speketer, K., Carvajal, L., Carvalho, S., Croitoru, I., Garrido, A., Payne, L., Viswanth, V., Severt, L., Facheris, M., Soares, H., Mintun, M. A., Cedarbaum, J., Taylor, P., Biglan, K., Vandenbroucke, E., Sheikh, Z., Bingol, B., Fischer, T., Sardi, P., Forrat, R., Reith, A., Egebjerg, J., Hillert, G., Saba, B., Min, C., Umek, R., Mather, J., De Santi, S., Post, A., Boess, F., Taylor, K., Grachev, I., Avbersek, A., Muglia, P., Merchant, K., Tauscher, J., Parkinsons Progression Markers, Study Cores, Site Investigators, Ind Sci Advisory Board 2019; 62: 201–9

    Abstract

    To determine the feasibility, safety and tolerability of lumbar punctures (LPs) in research participants with early Parkinson disease (PD), subjects without evidence of dopaminergic deficiency (SWEDDs) and healthy volunteers (HC).Cerebrospinal fluid (CSF) analysis is becoming an essential part of the biomarkers discovery effort in PD with still limited data on safety and feasibility of serial LPs in PD participants.Parkinson's Progression Marker Initiative (PPMI) is a longitudinal observation study designed to identify PD progression biomarkers. All PPMI participants undergo LP at baseline, 6, 12 months and yearly thereafter. CSF collection is performed by a trained investigator using predominantly atraumatic needles. Adverse events (AEs) are monitored by phone one week after LP completion. We analyzed safety data from baseline LPs.PPMI enrolled 683 participants (423 PD/196 HC/64 SWEDDs) from 23 study sites. CSF was collected at baseline in 97.5% of participants, of whom 5.4% underwent collection under fluoroscopy. 23% participants reported any related AEs, 68% of all AE were mild while 5.6% were severe. The most common AEs were headaches (13%) and low back pain (6.5%) and both occurred more commonly in HC and SWEDDs compared to PD participants. Factors associated with higher incidence of AEs across the cohorts included female gender, younger age and use of traumatic needles with larger diameter. AEs largely did not impact compliance with the future LPs.LPs are safe and feasible in PD research participants. Specific LP techniques (needle type and gauge) may reduce the overall incidence of AEs.

    View details for DOI 10.1016/j.parkreldis.2018.12.025

    View details for Web of Science ID 000476961700032

    View details for PubMedID 30738748

  • Self-reported physical activity levels and clinical progression in early Parkinson's disease PARKINSONISM & RELATED DISORDERS Amara, A. W., Chahine, L., Seedorff, N., Caspell-Garcia, C. J., Coffey, C., Simuni, T., Marek, K., Daegelel, N., Tanner, C., Simuni, T., Coffey, C., Kieburtz, K., Wilsons, R., Mollenhauer, B., Galasko, D., Foroud, T., Chahine, L., Siderowf, A., Seibyl, J., Toga, A., Singleton, A., Weintraub, D., Trojanowski, J., Shaw, L., Tosun-Turgut, D., Poston, K., Bressman, S., Merchant, K. M., Poewe, W., Sherer, T., Chowdhury, S., Frasier, M., Kopil, C., Naito, A., Arnedo, V., Dorsey, R., Casaceli, C., Daegele, N., Albani, J., Caspell-Garcia, C., Uribe, L., Foster, E., Long, J., Seedorff, N., Crawford, K., Smiths, D., Casalin, P., Malferrari, G., Halter, C., Heathers, L., Russell, D., Factor, S., Hogarth, P., Standaert, D., Amara, A., Hauser, R., Jankovic, J., Dahodwala, N., Stern, M., Hu, S., Todd, G., Saunders-Pullman, R., Richard, I., Saint-Hilaire, M. H., Seppi, K., Shill, H., Fernandez, H., Trenkwalder, C., Oertel, W., Berg, D., Brockman, K., Wurster, I., Rosenthal, L., Tai, Y., Pavese, N., Barone, P., Isaacson, S., Espay, A., Rowe, D., Brandabur, M., Tetrud, J., Liang, G., Iranzo, A., Tolosa, E., Marder, K., Sanchez, M., Stefanis, L., Jose Marti, M., Ruiz Martinez, J., Corvol, J., Assly, J., Brillman, S., Giladi, N., Smejdir, D., Pelaggi, J., Kausar, F., Rees, L., Sommerfield, B., Freed, A., Blair, C., Williams, K., Zimmerman, G., Guthrie, S., Rawlins, A., Donhar, L., Hunter, C., Tran, B., Darin, A., Linder, C., Baca, M., Venkov, H., Thomas, C., James, R., Heim, B., Deritis, P., Sprenger, F., Raymond, D., Willeke, D., Obradov, Z., Mule, J., Monahan, N., Gauss, K., Fontaine, D., Szpak, D., Mccoy, A., Dunlop, B., Payne, L., Ainscough, S., Carvajal, L., Silverstein, R., Espay, K., Ranola, M., Mondragon Rezola, E., Mejia Santana, H., Stamelou, M., Garrido, A., Carvalho, S., Kristiansen, A., Specketer, K., Mirlman, A., Facheris, M., Soares, H., Mintun, M. A., Cedarbaum, J., Taylor, P., Jennings, D., Slieker, L., McBride, B., Watson, C., Montagut, E., Sheikh, Z., Bingol, B., Forrat, R., Sardi, P., Fischer, T., Reith, A. D., Egebjerg, J., Larsen, L., Breysse, N., Meulien, D., Saba, B., Kiyasova, V., Min, C., McAvoy, T., Umek, R., Iredale, P., Edgerton, J., De Sand, S., Czech, C., Boess, F., Sevigny, J., Kremer, T., Grachev, I., Merchant, K., Avbersek, A., Muglia, P., Stewart, A., Prashad, R., Taucher, J., Parkinsons Progression Markers 2019; 61: 118–25

    Abstract

    This study investigates longitudinal changes in self-reported physical activity, measured by Physical Activity Scale of the Elderly (PASE), in early Parkinson's disease (PD) and matched healthy control (HC) participants in the Parkinson's Progression Marker Initiative (PPMI) and evaluates associations between physical activity and PD progression.PPMI is a prospective, longitudinal study evaluating markers of progression in PD participants who are unmedicated at enrollment. PASE, a self-reported measure of physical activity, was administered to early PD (N = 380) and HC (N = 174). PASE was introduced after study launch and therefore administered at years 2, 3, and 4. PASE scores for PD and HC were compared with t-tests and changes over time were evaluated with generalized estimating equations.There were no differences in activity levels between PD and HC at any time point. However, PD participants had a longitudinal decrease in PASE from years two to four (p = 0.034), while HC did not (p = 0.89). In exploratory analyses controlling for age, sex, and disease duration, higher self-reported activity at year 2 were associated with slower progression of motor symptoms (p = 0.018), ADL performance (p < 0.0001), depression (p = 0.001), anxiety (p = 0.002), and cognitive decline (p = 0.016) over two years. These findings remained significant after adjusting for disease severity.There are no differences in self-reported physical activity between HC and early PD, but activity levels decline longitudinally in PD. Exploratory analyses show that higher self-reported physical activity is associated with less disease progression. Therefore, interventions to increase physical activity in early PD could potentially modify the disease course.

    View details for DOI 10.1016/j.parkreldis.2018.11.006

    View details for Web of Science ID 000468719900021

    View details for PubMedID 30554993

  • Episodic recognition memory and the hippocampus in Parkinson's disease: A review CORTEX Das, T., Hwang, J. J., Poston, K. L. 2019; 113: 191–209
  • Cognitive Performance in Parkinson's Disease in the Brain Health Registry. Journal of Alzheimer's disease : JAD Cholerton, B., Weiner, M. W., Nosheny, R. L., Poston, K. L., Scott Mackin, R., Tian, L., Ashford, J. W., Montine, T. J. 2019

    Abstract

    The study of cognition in Parkinson's disease (PD) traditionally requires exhaustive recruitment strategies. The current study examines data collected by the Brain Health Registry (BHR) to determine whether ongoing efforts to improve the recruitment base for therapeutic trials in Alzheimer's disease may be similarly effective for PD research, and whether online cognitive measurements can discriminate between participants who do and do not report a PD diagnosis. Participants enrolled in the BHR (age ≥50) with self-reported PD data and online cognitive testing available were included (n = 11,813). Associations between baseline cognitive variables and diagnostic group were analyzed using logistic regression. Linear mixed effects models were used to analyze longitudinal data. A total of 634 participants reported PD diagnosis at baseline with no self-reported cognitive impairment and completed cognitive testing. Measures of visual learning and memory, processing speed, attention, and working memory discriminated between self-reported PD and non-PD participants after correcting for multiple comparisons (p values <  0.006). Scores on all cognitive tests improved over time in PD and controls with the exception of processing speed, which remained stable in participants with PD while improving in those without. We demonstrate that a novel online approach to recruitment and longitudinal follow-up of study participants is effective for those with self-reported PD, and that significant differences exist between those with and without a reported diagnosis of PD on computerized cognitive measures. These results have important implications for recruitment of participants with PD into targeted therapeutic trials or large-scale genetic and cognitive studies.

    View details for PubMedID 30909225

  • Lewy Body Dementia Association's Research Centers of Excellence Program: Inaugural Meeting Proceedings. Alzheimer's research & therapy Peterson, B., Armstrong, M., Galasko, D., Galvin, J. E., Goldman, J., Irwin, D., Paulson, H., Kaufer, D., Leverenz, J., Lunde, A., McKeith, I. G., Siderowf, A., Taylor, A., Amodeo, K., Barrett, M., Domoto-Reilly, K., Duda, J., Gomperts, S., Graff-Radford, N., Holden, S., Honig, L., Huddleston, D., Lippa, C., Litvan, I., Manning, C., Marder, K., Moussa, C., Onyike, C., Pagan, F., Pantelyat, A., Pelak, V., Poston, K., Quinn, J., Richard, I., Rosenthal, L. S., Sabbagh, M., Scharre, D., Sha, S., Shill, H., Torres-Yaghi, Y., Christie, T., Graham, T., Richards, I., Koehler, M., Boeve, B. 2019; 11 (1): 23

    Abstract

    The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator's meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or other) professionals, and (4) create infrastructure for a clinical trials-ready network as well as resources to advance the study of new therapeutics.

    View details for PubMedID 30867052

  • Comparative sensitivity of the MoCA and Mattis Dementia Rating Scale-2 in Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society Hendershott, T. R., Zhu, D., Llanes, S., Zabetian, C. P., Quinn, J., Edwards, K. L., Leverenz, J. B., Montine, T., Cholerton, B., Poston, K. L. 2019; 34 (2): 285–91

    Abstract

    BACKGROUND: Clinicians and researchers commonly use global cognitive assessments to screen for impairment. Currently there are no published studies directly comparing the sensitivity and specificity of the Montreal Cognitive Assessment and Mattis Dementia Rating Scale-2 in PD. The objective of this study was to identify the relative sensitivity and specificity of the Montreal Cognitive Assessment and Mattis Dementia Rating Scale-2 in PD.METHODS: The Montreal Cognitive Assessment and Mattis Dementia Rating Scale-2 were administered to training and validation cohorts. Cutoff scores were determined within the training cohort (n = 85) to optimize sensitivity and specificity for cognitive impairment and were applied to an independent validation cohort (n = 521).RESULTS: The Montreal Cognitive Assessment was consistently sensitive across training and validation cohorts (90.0% and 80.3%, respectively), whereas the Mattis Dementia Rating Scale-2 was not (87.5% and 60.3%, respectively). In individual domains, the Montreal Cognitive Assessment remained sensitive to memory and visuospatial impairments (91.9% and 87.8%, respectively), whereas the Mattis Dementia Rating Scale-2 was sensitive to executive impairments (86.2%).CONCLUSION: The Montreal Cognitive Assessment and Mattis Dementia Rating Scale-2 demonstrated individual strengths. Future work should focus on developing domain-specific cognitive screening tools for PD. © 2018 International Parkinson and Movement Disorder Society.

    View details for PubMedID 30776152

  • Cognitive Performance in Parkinson's Disease in the Brain Health Registry JOURNAL OF ALZHEIMERS DISEASE Cholerton, B., Weiner, M. W., Nosheny, R. L., Poston, K. L., Mackin, R., Tian, L., Ashford, J., Montine, T. J. 2019; 68 (3): 1029–38

    View details for DOI 10.3233/JAD-181009

    View details for Web of Science ID 000464031500013

  • Cognitive associations with comprehensive gait and static balance measures in Parkinson's disease. Parkinsonism & related disorders Morris, R., Martini, D. N., Smulders, K., Kelly, V. E., Zabetian, C. P., Poston, K., Hiller, A., Chung, K. A., Yang, L., Hu, S. C., Edwards, K. L., Cholerton, B., Grabowski, T. J., Montine, T. J., Quinn, J. F., Horak, F. 2019; 69: 104–10

    Abstract

    Gait and balance impairments are cardinal features of Parkinson's disease (PD) that require cognitive input. However, the extent to which specific gait and balance characteristics relate to cognition in PD is unclear. In addition, independent models of gait and balance have not been developed from the same cohort. We aimed to i) develop models of gait and balance in a large PD cohort and ii) determine which gait and balance characteristics best related to cognition.One hundred and ninety-eight people with PD were recruited to the Pacific Udall Center. Using six inertial sensors (APDM, Inc.), comprehensive gait measurements were collected over a 2-min continuous walk and comprehensive static balance measures were collected during a 60-second standing task. Six domains of cognition were assessed: global cognition, attention, executive function, language, memory, and visuospatial function. Correlations and hierarchical linear regression determined independent associations.Principal components analysis identified a gait model containing four domains accounting for 80.1% of total variance: pace/turning, rhythm, variability, and trunk. The balance model contained four independent domains accounting for 84.5% of total variance: sway area/jerkiness, sway velocity, sway frequency anteroposterior, and sway frequency mediolateral. Gait domains of pace/turning and variability were strongly associated with attention and executive function. Sway area and jerkiness of balance associated with attention and visuospatial function.Gait and balance characteristics were associated with specific types of cognition. The specific relationships between gait or balance with cognitive functions suggests shared cerebral cortical circuitry for mobility and cognitive functions.

    View details for DOI 10.1016/j.parkreldis.2019.06.014

    View details for PubMedID 31731260

  • Predicting Progression in Parkinson's Disease Using Baseline and 1-Year Change Measures JOURNAL OF PARKINSONS DISEASE Chahine, L. M., Siderowf, A., Barnes, J., Seedorff, N., Caspell-Garcia, C., Simuni, T., Coffey, C. S., Galasko, D., Mollenhauer, B., Arnedo, V., Daegele, N., Frasier, M., Tanner, C., Kieburtz, K., Marek, K., Seibyl, J., Coffey, C., Tosun-Turgut, D., Shaw, L., Trojanowski, J., Singleton, A., Toga, A., Chahine, L., Poewe, W., Foroud, T., Poston, K., Sherer, T., Chowdhury, S., Kopil, C., Casaceli, C., Dorsey, R., Wilson, R., Mahes, S., Salerno, C., Crawford, K., Casalin, P., Malferrari, G., Weisz, M., Orr-Urtreger, A., Montine, T., Russell, D., Dahodwala, N., Giladi, N., Factor, S., Hogarth, P., Standaert, D., Hauser, R., Jankovic, J., Saint-Hilaire, M., Richard, I., Shprecher, D., Fernandez, H., Brockmann, K., Rosenthal, L., Barone, P., Espay, A., Rowe, D., Marder, K., Santiago, A., Bressman, S., Hu, S., Isaacson, S., Corvol, J., Ruiz Martinez, J., Tolosa, E., Tai, Y., Politis, M., Smejdir, D., Rees, L., Williams, K., Kausar, F., Richardson, W., Willeke, D., Peacock, S., Sommerfeld, B., Freed, A., Wakeman, K., Blair, C., Guthrie, S., Harrell, L., Hunter, C., Thomas, C., James, R., Zimmerman, G., Brown, V., Mule, J., Hilt, E., Ribb, K., Ainscough, S., Wethington, M., Ranola, M., Santana, H., Moreno, J., Raymond, D., Speketer, K., Carvajal, L., Carvalho, S., Croitoru, I., Garrido, A., Payne, L., Viswanth, V., Severt, L., Facheris, M., Soares, H., Mintun, M. A., Cedarbaum, J., Taylor, P., Biglan, K., Vandenbroucke, E., Sheikh, Z., Bingol, B., Fischer, T., Sardi, P., Forrat, R., Reith, A., Egebjerg, J., Hillert, G., Saba, B., Min, C., Umek, R., Mather, J., De Santi, S., Post, A., Boess, F., Taylor, K., Grachev, I., Avbersek, A., Muglia, P., Merchant, K., Tauscher, J., Parkinsons Progression Markers Ini 2019; 9 (4): 665–79

    Abstract

    Improved prediction of Parkinson's disease (PD) progression is needed to support clinical decision-making and to accelerate research trials.To examine whether baseline measures and their 1-year change predict longer-term progression in early PD.Parkinson's Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models.Among 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (β= 0.351; 95% CI = 0.146, 0.555), male gender (β= 3.090; 95% CI = 0.310, 5.869), and baseline (β= -0.199; 95% CI = -0.315, -0.082) and 1-year change (β= 0.540; 95% CI = 0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (β= -0.6229; 95% CI = -1.2910, 0.0452), baseline (β= 7.232; 95% CI = 2.268, 12.195) and 1-year change (β= 45.918; 95% CI = 35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (β= -0.325;95% CI = -0.695, 0.045); predictors in the model accounted for 44.1% of the variance.Baseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved the predictive value, especially for modeling change in dopamine-transporter binding.

    View details for DOI 10.3233/JPD-181518

    View details for Web of Science ID 000489899800003

    View details for PubMedID 31450510

  • MRI biomarkers of motor and non-motor symptoms in Parkinson's disease. Parkinsonism & related disorders Ryman, S. G., Poston, K. L. 2019

    Abstract

    Parkinson's disease is a heterogeneous disorder with both motor and non-motor symptoms that contribute to functional impairment. To develop effective, disease modifying treatments for these symptoms, biomarkers are necessary to detect neuropathological changes early in the disease course and monitor changes over time. Advances in MRI scan sequences and analytical techniques present numerous promising metrics to detect changes within the nigrostriatal system, implicated in the cardinal motor symptoms of the disease, and detect broader dysfunction involved in the non-motor symptoms, such as cognitive impairment. There is emerging evidence that iron sensitive, neuromelanin sensitive, diffusion sensitive, and resting state functional magnetic imaging measures can capture changes within the nigrostriatal system. Iron, neuromelanin, and diffusion sensitive measures demonstrate high specificity and sensitivity in distinguishing Parkinson's disease relative to controls, with inconsistent results differentiating Parkinson's disease relative to atypical parkinsonian disorders. They may also serve as useful monitoring biomarkers, with each possibly detecting different aspects of the disease course (early nigrosome changes versus broader substantia nigra changes). Investigations of non-motor symptoms, such as cognitive impairment, require careful consideration of the nature of cognitive deficits to characterize regional and network specific impairment. While the early, executive dysfunction observed is consistent with nigrostriatal degeneration, the memory and visuospatial impairments, the harbingers of a dementia process reflect dopaminergic independent dysfunction involving broader regions of the brain.

    View details for DOI 10.1016/j.parkreldis.2019.10.002

    View details for PubMedID 31629653

  • Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease. NeuroImage. Clinical La, C., Linortner, P., Bernstein, J. D., Ua Cruadhlaoich, M. A., Fenesy, M., Deutsch, G. K., Rutt, B. K., Tian, L., Wagner, A. D., Zeineh, M., Kerchner, G. A., Poston, K. L. 2019; 23: 101824

    Abstract

    Parkinson's disease (PD) episodic memory impairments are common; however, it is not known whether these impairments are due to hippocampal pathology. Hippocampal Lewy-bodies emerge by Braak stage 4, but are not uniformly distributed. For instance, hippocampal CA1 Lewy-body pathology has been specifically associated with pre-mortem episodic memory performance in demented patients. By contrast, the dentate gyrus (DG) is relatively free of Lewy-body pathology. In this study, we used ultra-high field 7-Tesla to measure hippocampal subfields in vivo and determine if these measures predict episodic memory impairment in PD during life.We studied 29 participants with PD (age 65.5 ± 7.8 years; disease duration 4.5 ± 3.0 years) and 8 matched-healthy controls (age 67.9 ± 6.8 years), who completed comprehensive neuropsychological testing and MRI. With 7-Tesla MRI, we used validated segmentation techniques to estimate CA1 stratum pyramidale (CA1-SP) and stratum radiatum lacunosum moleculare (CA1-SRLM) thickness, dentate gyrus/CA3 (DG/CA3) area, and whole hippocampus area. We used linear regression, which included imaging and clinical measures (age, duration, education, gender, and CSF), to determine the best predictors of episodic memory impairment in PD.In our cohort, 62.1% of participants with PD had normal cognition, 27.6% had mild cognitive impairment, and 10.3% had dementia. Using 7-Tesla MRI, we found that smaller CA1-SP thickness was significantly associated with poorer immediate memory, delayed memory, and delayed cued memory; by contrast, whole hippocampus area, DG/CA3 area, and CA1-SRLM thickness did not significantly predict memory. Age-adjusted linear regression models revealed that CA1-SP predicted immediate memory (beta[standard error]10.895[4.215], p < .05), delayed memory (12.740[5.014], p < .05), and delayed cued memory (12.801[3.991], p < .05). In the fully-adjusted models, which included all five clinical measures as covariates, only CA1-SP remained a significant predictor of delayed cued memory (13.436[4.651], p < .05).In PD, we found hippocampal CA1-SP subfield thickness estimated on 7-Tesla MRI scans was the best predictor of episodic memory impairment, even when controlling for confounding clinical measures. Our results imply that ultra-high field imaging could be a sensitive measure to identify changes in hippocampal subfields and thus probe the neuroanatomical underpinnings of episodic memory impairments in patients with PD.

    View details for PubMedID 31054380

  • Ultra-Low-Dose 18F-Florbetaben Amyloid PET Imaging Using Deep Learning with Multi-Contrast MRI Inputs. Radiology Chen, K. T., Gong, E., de Carvalho Macruz, F. B., Xu, J., Boumis, A., Khalighi, M., Poston, K. L., Sha, S. J., Greicius, M. D., Mormino, E., Pauly, J. M., Srinivas, S., Zaharchuk, G. 2018: 180940

    Abstract

    Purpose To reduce radiotracer requirements for amyloid PET/MRI without sacrificing diagnostic quality by using deep learning methods. Materials and Methods Forty data sets from 39 patients (mean age ± standard deviation [SD], 67 years ± 8), including 16 male patients and 23 female patients (mean age, 66 years ± 6 and 68 years ± 9, respectively), who underwent simultaneous amyloid (fluorine 18 [18F]-florbetaben) PET/MRI examinations were acquired from March 2016 through October 2017 and retrospectively analyzed. One hundredth of the raw list-mode PET data were randomly chosen to simulate a low-dose (1%) acquisition. Convolutional neural networks were implemented with low-dose PET and multiple MR images (PET-plus-MR model) or with low-dose PET alone (PET-only) as inputs to predict full-dose PET images. Quality of the synthesized images was evaluated while Bland-Altman plots assessed the agreement of regional standard uptake value ratios (SUVRs) between image types. Two readers scored image quality on a five-point scale (5 = excellent) and determined amyloid status (positive or negative). Statistical analyses were carried out to assess the difference of image quality metrics and reader agreement and to determine confidence intervals (CIs) for reading results. Results The synthesized images (especially from the PET-plus-MR model) showed marked improvement on all quality metrics compared with the low-dose image. All PET-plus-MR images scored 3 or higher, with proportions of images rated greater than 3 similar to those for the full-dose images (-10% difference [eight of 80 readings], 95% CI: -15%, -5%). Accuracy for amyloid status was high (71 of 80 readings [89%]) and similar to intrareader reproducibility of full-dose images (73 of 80 [91%]). The PET-plus-MR model also had the smallest mean and variance for SUVR difference to full-dose images. Conclusion Simultaneously acquired MRI and ultra-low-dose PET data can be used to synthesize full-dose-like amyloid PET images. © RSNA, 2018 Online supplemental material is available for this article.

    View details for PubMedID 30526350

  • Episodic recognition memory and the hippocampus in Parkinson's disease: A review. Cortex; a journal devoted to the study of the nervous system and behavior Das, T., Hwang, J. J., Poston, K. L. 2018; 113: 191–209

    Abstract

    Parkinson's disease is a progressive neurodegenerative disorder of aging. The hallmark pathophysiology includes the development of neuronal Lewy bodies in the substantia nigra of the midbrain with subsequent loss of dopaminergic neurons. These neuronal losses lead to the characteristic motor symptoms of bradykinesia, rigidity, and rest tremor. In addition to these cardinal motor symptoms patients with PD experience a wide range of non-motor symptoms, the most important being cognitive impairments that in many circumstances lead to dementia. People with PD experience a wide range of cognitive impairments; in this review we will focus on memory impairment in PD and specifically episodic memory, which are memories of day-to-day events of life. Importantly, these memory impairments severely impact the lives of patients and caregivers alike. Traditionally episodic memory is considered to be markedly dependent on the hippocampus; therefore, it is important to understand the exact nature of PD episodic memory deficits in relation to hippocampal function and dysfunction. In this review, we discuss an aspect of episodic memory called recognition memory and its subcomponents called recollection and familiarity. Recognition memory is believed to be impaired in PD; thus, we discuss what aspects of the hippocampus are expected to be deficient in function as they relate to these recognition memory impairments. In addition to the hippocampus as a whole, we will discuss the role of hippocampal subfields in recognition memory impairments.

    View details for PubMedID 30660957

  • The Parkinson's progression markers initiative (PPMI) - establishing a PD biomarker cohort. Annals of clinical and translational neurology Marek, K., Chowdhury, S., Siderowf, A., Lasch, S., Coffey, C. S., Caspell-Garcia, C., Simuni, T., Jennings, D., Tanner, C. M., Trojanowski, J. Q., Shaw, L. M., Seibyl, J., Schuff, N., Singleton, A., Kieburtz, K., Toga, A. W., Mollenhauer, B., Galasko, D., Chahine, L. M., Weintraub, D., Foroud, T., Tosun-Turgut, D., Poston, K., Arnedo, V., Frasier, M., Sherer, T., Parkinson's Progression Markers Initiative, Bressman, S., Merchant, M., Poewe, W., Kopil, C., Naito, A., Dorsey, R., Casaceli, C., Daegele, N., Albani, J., Uribe, L., Foster, E., Long, J., Seedorff, N., Crawford, K., Smith, D., Casalin, P., Malferrari, G., Halter, C., Heathers, L., Russell, D., Factor, S., Hogarth, P., Amara, A., Hauser, R., Jankovic, J., Stern, M., Hu, S., Todd, G., Saunders-Pullman, R., Richard, I., Saint-Hilaire, H., Seppi, K., Shill, H., Fernandez, H., Trenkwalder, C., Oertel, W., Berg, D., Brockman, K., Wurster, I., Rosenthal, L., Tai, Y., Pavese, N., Barone, P., Isaacson, S., Espay, A., Rowe, D., Brandabur, M., Tetrud, J., Liang, G., Iranzo, A., Tolosa, E., Marder, K., de Sanchez, M., Stefanis, L., Marti, M., Martinez, J., Corvol, J., Assly, O., Brillman, S., Giladi, N., Smejdir, D., Pelaggi, J., Kausar, F., Rees, L., Sommerfield, B., Cresswell, M., Blair, C., Williams, K., Zimmerman, G., Guthrie, S., Rawlins, A., Donharl, L., Hunter, C., Tran, B., Darin, A., Venkov, H., Thomas, C., James, R., Heim, B., Deritis, P., Sprenger, F., Raymond, D., Willeke, D., Obradov, Z., Mule, J., Monahan, N., Gauss, K., Fontaine, D., Szpak, D., McCoy, A., Dunlop, B., Payne, L., Ainscough, S., Carvajal, L., Silverstein, R., Espay, K., Ranola, M., Rezola, E., Santana, H., Stamelou, M., Garrido, A., Carvalho, S., Kristiansen, G., Specketer, K., Mirlman, A., Facheris, M., Soares, H., Mintun, A., Cedarbaum, J., Taylor, P., Jennings, D., Slieker, L., McBride, B., Watson, C., Montagut, E., Sheikh, Z., Bingol, B., Forrat, R., Sardi, P., Fischer, T., Reith, D., Egebjerg, J., Larsen, L., Breysse, N., Meulien, D., Saba, B., Kiyasova, V., Min, C., McAvoy, T., Umek, R., Iredale, P., Edgerton, J., Santi, D., Czech, C., Boess, F., Sevigny, J., Kremer, T., Grachev, I., Merchant, K., Avbersek, A., Muglia, P., Stewart, A., Prashad, R., Taucher, J. 2018; 5 (12): 1460–77

    Abstract

    Objective: The Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials.Methods: A total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org.Results: Approximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) alpha-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P<0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P<0.01).Interpretation: PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.

    View details for PubMedID 30564614

  • Information processing deficit in older adults with HIV infection: A comparison with Parkinson's disease. Neuropsychology Sundaram, S., Muller-Oehring, E. M., Fama, R., Bronte-Stewart, H. M., Poston, K. L., Goodcase, R., Martin, T., Prabhakar, V., Karpf, J., Schulte, T. 2018

    Abstract

    OBJECTIVE: Individuals with HIV treated with antiretroviral therapy can expect to reach average life span, making them susceptible to combined disease and aging effects on cognitive and motor functions. Slowed processing speed in HIV is a concern for cognitive and everyday functioning and is sensitive to declines in aging. We hypothesized that information processing (IP) deficits, over and above that expected with normal aging, would occur in older HIV patients similar to those observed in Parkinson's disease (PD) patients, with both conditions affecting frontostriatal pathways.METHOD: Groups comprised 26 individuals with HIV infection, 29 with mild-to-moderate PD, and 21 healthy controls (C). Speed of IP was assessed with the oral version of the Symbol Digit Modalities Test and the color naming condition of the Golden Stroop Task.RESULTS: The HIV group was impaired on speed of IP tasks compared with both the C and PD groups. Even after controlling for normal aging effects, older age in the HIV group correlated with IP slowing. Slower IP speed was associated with poorer general cognitive ability and more extrapyramidal motor signs in older HIV-infected individuals.CONCLUSIONS: The notable effects of impaired IP speed, over and above neurotypical age-related declines, indicate that older HIV-infected individuals may have an enhanced vulnerability for developing nonmotor and motor symptoms despite antiretroviral therapy. Assessing for oral IP speed may provide the unique opportunity to identify early signs of progressive clinical declines in HIV. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

    View details for PubMedID 30475047

  • Further study of the Montreal Cognitive Assessment's domain-specific metrics could allow for international data comparison and collaboration PARKINSONISM & RELATED DISORDERS Hendershott, T. R., Poston, K. L. 2018; 48: 101

    View details for PubMedID 29221675

  • Slower saccadic reading in Parkinson's disease PLOS ONE Jehangir, N., Yu, C., Song, J., Shariati, M., Binder, S., Beyer, J., Santini, V., Poston, K., Liao, Y. 2018; 13 (1): e0191005

    Abstract

    Idiopathic Parkinson's Disease (PD) is characterized by degeneration of dopaminergic and other neurons, leading to motor and non-motor deficits. Abnormal eye movements in PD, including fixations, saccades, and convergence, are well described. However, saccadic reading, which requires serial and alternating saccades and fixations, is not well studied, despite its obvious impact on the quality of life. In this study, we assessed saccadic reading using variations of the King-Devick (KD) test, a rapid single digit number naming test, as a way to assess the ability to make serial left-to-right ocular motor movements necessary for reading. We recruited 42 treated PD patients and 80 age-matched controls and compared their reading times with a variety of measures, including age, duration of disease, Unified Parkinson's Disease Rating Scale (UPDRS), the National Eye Institute 25-Item Visual Functioning Questionnaire 25 (VFQ-25), and Montreal Cognitive assessment (MoCA) test. The subjects performed 4 trials of reading 120 single digit numbers aloud as fast as possible without making errors. In each trial, they read 3 pages (KD1, KD2, and KD3), and each page contained 40 numbers per page in 8 lines with 5 numbers/line. We found that PD patients read about 20% slower than controls on all tests (KD1, 2, and 3 tests) (p < 0.02), and both groups read irregularly spaced numbers slower than regularly spaced numbers. Having lines between numbers to guide reading (KD1 tests) did not impact reading time in both PD and controls, but increased visual crowding as a result of decreased spacing between numbers (KD3 tests) was associated with significantly slower reading times in both PD and control groups. Our study revealed that saccadic reading is slower in PD, but controls and PD patients are both impacted by visuospatial planning challenges posed by increased visual crowding and irregularity of number spacing. Reading time did not correlate with UPDRS or MoCA scores in PD patients but significantly correlated with age, duration of disease, and VFQ-25 scores. The presence of convergence insufficiency did not significantly correlate with reading time in PD patients, although on average there was slower reading time in those with convergence insufficiency by 8 s (p = 0.2613). We propose that a simple reading task using 120 single-digit numbers can be used as a screening tool in the clinical setting to assess functional ocular motor difficulties in Parkinson's disease that can have a profound impact on quality of life.

    View details for PubMedID 29364897

  • gene therapy trial for Parkinson's disease. JCI insight Niethammer, M., Tang, C. C., LeWitt, P. A., Rezai, A. R., Leehey, M. A., Ojemann, S. G., Flaherty, A. W., Eskandar, E. N., Kostyk, S. K., Sarkar, A., Siddiqui, M. S., Tatter, S. B., Schwalb, J. M., Poston, K. L., Henderson, J. M., Kurlan, R. M., Richard, I. H., Sapan, C. V., Eidelberg, D., During, M. J., Kaplitt, M. G., Feigin, A. 2017; 2 (7)

    Abstract

    BACKGROUND. We report the 12-month clinical and imaging data on the effects of bilateral delivery of the glutamic acid decarboxylase gene into the subthalamic nuclei (STN) of advanced Parkinson's disease (PD) patients. METHODS. 45 PD patients were enrolled in a 6-month double-blind randomized trial of bilateral AAV2-GAD delivery into the STN compared with sham surgery and were followed for 12 months in open-label fashion. Subjects were assessed with clinical outcome measures and (18)F-fluorodeoxyglucose (FDG) PET imaging. RESULTS. Improvements under the blind in Unified Parkinson's Disease Rating Scale (UPDRS) motor scores in the AAV2-GAD group compared with the sham group continued at 12 months [time effect: F(4,138) = 11.55, P < 0.001; group effect: F(1,35) = 5.45, P < 0.03; repeated-measures ANOVA (RMANOVA)]. Daily duration of levodopa-induced dyskinesias significantly declined at 12 months in the AAV2-GAD group (P = 0.03; post-hoc Bonferroni test), while the sham group was unchanged. Analysis of all FDG PET images over 12 months revealed significant metabolic declines (P < 0.001; statistical parametric mapping RMANOVA) in the thalamus, striatum, and prefrontal, anterior cingulate, and orbitofrontal cortices in the AAV2-GAD group compared with the sham group. Across all time points, changes in regional metabolism differed for the two groups in all areas, with significant declines only in the AAV2-GAD group (P < 0.005; post-hoc Bonferroni tests). Furthermore, baseline metabolism in the prefrontal cortex (PFC) correlated with changes in motor UPDRS scores; the higher the baseline PFC metabolism, the better the clinical outcome. CONCLUSION. These findings show that clinical benefits after gene therapy with STN AAV2-GAD in PD patients persist at 12 months. TRIAL REGISTRATION. ClinicalTrials.gov NCT00643890. FUNDING. Neurologix Inc.

    View details for DOI 10.1172/jci.insight.90133

    View details for PubMedID 28405611

  • Domain-specific accuracy of the Montreal Cognitive Assessment subsections in Parkinson's disease. Parkinsonism & related disorders Hendershott, T. R., Zhu, D., Llanes, S., Poston, K. L. 2017

    Abstract

    The Montreal Cognitive Assessment (MoCA) is among the most widely adopted screening tools for cognitive impairment because it includes tests in multiple domains and is available in 55 languages. The MoCA is often the only formal cognitive assessment available when comprehensive neuropsychological testing is not practical, such as rural clinical settings or large retrospective and multi-lingual research settings. However, the MoCA domain-specific subsections have never been formally assessed for sensitivity or specificity. Therefore, in Parkinson's disease, we examined whether the subsections of the MoCA could identify cognitive impairment within specific cognitive domains.We administered a comprehensive neuropsychological battery to 85 Parkinson's disease participants, who were then categorized as with or without cognitive impairment, with respect to global cognition and in five cognitive domains. We then assessed the domain-specific categorization of the MoCA subsections compared to the full neuropsychology battery.All MoCA subsections predicted impairment in their respective cognitive domain. However, the executive subsection showed the highest sensitivity and specificity (89.3% and 82.5%, respectively), followed by visuospatial (93.3% and 45.7%, respectively) and memory (84.6% and 56.5%, respectively).The MoCA is a useful screening tool for PD global cognitive and executive functions. The MoCA is also highly sensitive to visuospatial and memory impairment, but with limited specificity and accuracy these subsections should be interpreted with caution.

    View details for DOI 10.1016/j.parkreldis.2017.02.008

    View details for PubMedID 28215728

    View details for PubMedCentralID PMC5400012

  • Abnormal eye movement behavior during reading in Parkinson's disease PARKINSONISM & RELATED DISORDERS Yu, C. Y., Lee, T., Shariati, A., Santini, V., Poston, K., Liao, Y. 2016; 32: 130–32

    Abstract

    Reading difficulties are common in Parkinson's disease (PD) but not well studied. We report a case of reading difficulties in a 40-year-old man with 6-year history of PD on dopamine replacement therapy.We performed detailed neuro-ophthalmic examination and assessment of reading with and without infrared oculography.Clinical examination revealed visual acuity of 20/20, no evidence of vision loss, and normal eye movement and ocular alignment with normal saccades, pursuit, and normal convergence. During King-Devick test, a rapid number reading task performed on a book, patient had normal number reading speed. More detailed study of number and word reading using infrared oculography revealed that while this patient had normal speed and eye movement behavior during number reading, he had dramatic slowing and eye movement abnormality during word reading. The slower reading speed during word reading was due to increased number of progressive saccades, smaller saccade amplitudes, increased number of regressive saccades, and longer fixation durations.This case nicely illustrated the importance of comprehensive neuro-ophthalmic evaluations in Parkinson's disease and shows that reading difficulties can arise even when there is good visual acuity, ocular motor abilities necessary to read, and accommodation. In this case, reading difficulty was due to higher order ocular motor planning or cognitive abilities involved in word reading since the patient had no difficulty with ocular motor planning while reading numbers. These findings may have important implications towards our understanding of PD and can serve to spark further research in this important area.

    View details for PubMedID 27592009

  • The effects of dopamine on digit span in Parkinson's disease. Journal of clinical movement disorders Warden, C., Hwang, J., Marshall, A., Fenesy, M., Poston, K. L. 2016; 3: 5-?

    Abstract

    Parkinson's disease patients are at an elevated risk of developing cognitive impairment. Although cognitive impairment is one of the strongest predictors of quality of life, dopaminergic anti-parkinsonian medications are designed to target motor symptoms. However, there is substantial evidence that dopamine also impacts cognition, in particular working memory. It is therefore critical for movement disorders physicians to understand the potential dopaminergic effects on working memory when prescribing these medications. Verbal digit span tasks offer a potentially straightforward and quick assessment of baseline working memory. Moreover, Digit Span Backward was recently validated as a screening tool for mild cognitive impairment in Parkinson's disease when participants were medicated. Research indicates that the interaction between dopamine and working memory follows an Inverted-U shaped curve, but the effect of dopamine on Digit Span has not been well studied. Our study seeks to: (1) determine the validity of verbal Digit Spans for detecting cognitive impairment in Parkinson's disease patients both ON and OFF medications; and (2) ascertain the effects of dopaminergic medications on verbal Digit Span.We recruited 64 Parkinson's disease patients and 22 age-and education-matched controls. Parkinson's patients completed Digit Span Backward and Digit Span Forward ON and OFF medications, while healthy controls completed them once. All participants were categorized by cognitive diagnosis using level-II consensus criteria.Digit Span Backward successfully identified mild cognitive impairment in Parkinson's disease, both ON and OFF medications. Combining patients with and without cognitive impairment, we found that dopamine significantly improved performance on Digit Span Backward, but not Forward. In a secondary analysis, we found this dopaminergic improvement was restricted to the Low baseline working memory group; the High baseline working memory group was unaffected.This study provides evidence for Digit Span Backward as a screening tool for working memory impairment in Parkinson's disease and for its utility in measuring baseline working memory. Moreover, it reveals a partial beneficial effect of dopamine on Digit Span in Parkinson's disease patients.

    View details for DOI 10.1186/s40734-016-0033-z

    View details for PubMedID 26955482

    View details for PubMedCentralID PMC4780147

  • Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease. Brain imaging and behavior Müller-Oehring, E. M., Sullivan, E. V., Pfefferbaum, A., Huang, N. C., Poston, K. L., Bronte-Stewart, H. M., Schulte, T. 2015; 9 (3): 619-638

    Abstract

    Parkinson's disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG-cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen-medial parietal and pallidum-occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate-supramarginal gyrus and pallidum-inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal-cortical connectivity, specifically between caudate-prefrontal, caudate-precuneus, and putamen-motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance.

    View details for DOI 10.1007/s11682-014-9317-9

    View details for PubMedID 25280970

    View details for PubMedCentralID PMC4385510

  • Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease BRAIN IMAGING AND BEHAVIOR Mueller-Oehring, E. M., Sullivan, E. V., Pfefferbaum, A., Huang, N. C., Poston, K. L., Bronte-Stewart, H. M., Schulte, T. 2015; 9 (3): 619-638

    Abstract

    Parkinson's disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG-cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen-medial parietal and pallidum-occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate-supramarginal gyrus and pallidum-inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal-cortical connectivity, specifically between caudate-prefrontal, caudate-precuneus, and putamen-motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance.

    View details for DOI 10.1007/s11682-014-9317-9

    View details for Web of Science ID 000361604300021

    View details for PubMedCentralID PMC4385510

  • Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double-blind, randomized, controlled trial. Annals of neurology Warren Olanow, C., Bartus, R. T., Baumann, T. L., Factor, S., Boulis, N., Stacy, M., Turner, D. A., Marks, W., Larson, P., Starr, P. A., Jankovic, J., Simpson, R., Watts, R., Guthrie, B., Poston, K., Henderson, J. M., Stern, M., Baltuch, G., Goetz, C. G., Herzog, C., Kordower, J. H., Alterman, R., Lozano, A. M., Lang, A. E. 2015; 78 (2): 248–57

    Abstract

    A 12-month double-blind sham-surgery-controlled trial assessing adeno-associated virus type 2 (AAV2)-neurturin injected into the putamen bilaterally failed to meet its primary endpoint, but showed positive results for the primary endpoint in the subgroup of subjects followed for 18 months and for several secondary endpoints. Analysis of postmortem tissue suggested impaired axonal transport of neurturin from putamen to substantia nigra. In the present study, we tested the safety and efficacy of AAV2-neurturin delivered to putamen and substantia nigra.We performed a 15- to 24-month, multicenter, double-blind trial in patients with advanced Parkinson disease (PD) who were randomly assigned to receive bilateral AAV2-neurturin injected bilaterally into the substantia nigra (2.0 × 10(11) vector genomes) and putamen (1.0 × 10(12) vector genomes) or sham surgery. The primary endpoint was change from baseline to final visit performed at the time the last enrolled subject completed the 15-month evaluation in the motor subscore of the Unified Parkinson's Disease Rating Scale in the practically defined off state.Fifty-one patients were enrolled in the trial. There was no significant difference between groups in the primary endpoint (change from baseline: AAV2-neurturin, -7.0 ± 9.92; sham, -5.2 ± 10.01; p = 0.515) or in most secondary endpoints. Two subjects had cerebral hemorrhages with transient symptoms. No clinically meaningful adverse events were attributed to AAV2-neurturin.AAV2-neurturin delivery to the putamen and substantia nigra bilaterally in PD was not superior to sham surgery. The procedure was well tolerated, and there were no clinically significant adverse events related to AAV2-neurturin. Ann Neurol 2015;78:248-257.

    View details for PubMedID 26061140

  • A disease-specific metabolic brain network associated with corticobasal degeneration BRAIN Niethammer, M., Tang, C. C., Feigin, A., Allen, P. J., Heinen, L., Hellwig, S., Amtage, F., Hanspal, E., Vonsattel, J. P., Poston, K. L., Meyer, P. T., Leenders, K. L., Eidelberg, D. 2014; 137: 3036-3046

    Abstract

    Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.9 ± 5.7 years) underwent metabolic brain imaging with (18)F-fluorodeoxyglucose positron emission tomography for atypical parkinsonism. These individuals were diagnosed clinically with probable corticobasal degeneration. This diagnosis was confirmed in the three subjects who additionally underwent post-mortem examination. Ten age-matched healthy subjects (five females/five males; age 71.7 ± 6.7 years) served as controls for the imaging studies. Spatial covariance analysis was applied to scan data from the combined group to identify a significant corticobasal degeneration-related metabolic pattern that discriminated (P < 0.001) the patients from the healthy control group. This pattern was characterized by bilateral, asymmetric metabolic reductions involving frontal and parietal cortex, thalamus, and caudate nucleus. These pattern-related changes were greater in magnitude in the cerebral hemisphere opposite the more clinically affected body side. The presence of this corticobasal degeneration-related metabolic topography was confirmed in two independent testing sets of patient and control scans, with elevated pattern expression (P < 0.001) in both disease groups relative to corresponding normal values. We next determined whether prospectively computed expression values for this pattern accurately discriminated corticobasal degeneration from multiple system atrophy and progressive supranuclear palsy (the two most common atypical parkinsonian syndromes) on a single case basis. Based upon this measure, corticobasal degeneration was successfully distinguished from multiple system atrophy (P < 0.001) but not progressive supranuclear palsy, presumably because of the overlap (∼ 24%) that existed between the corticobasal degeneration- and the progressive supranuclear palsy-related metabolic topographies. Nonetheless, excellent discrimination between these disease entities was achieved by computing hemispheric asymmetry scores for the corticobasal degeneration-related pattern on a prospective single scan basis. Indeed, a logistic algorithm based on the asymmetry scores combined with separately computed expression values for a previously validated progressive supranuclear palsy-related pattern provided excellent specificity (corticobasal degeneration: 92.7%; progressive supranuclear palsy: 94.1%) in classifying 58 testing subjects. In conclusion, corticobasal degeneration is associated with a reproducible disease-related metabolic covariance pattern that may help to distinguish this disorder from other atypical parkinsonian syndromes.

    View details for DOI 10.1093/brain/awu256

    View details for Web of Science ID 000346760900025

    View details for PubMedID 25208922

    View details for PubMedCentralID PMC4208467

  • What light have resting state fMRI studies shed on cognition and mood in Parkinson's disease? Journal of clinical movement disorders YorkWilliams, S., Poston, K. L. 2014; 1: 4-?

    Abstract

    Much remains unknown about non-motor symptoms of Parkinson's disease (PD), which have variable occurrence, progression, and severity among patients. The existing suite of neuroimaging tools has yielded insight that cannot be garnered by traditional methods such as behavioral and post-mortem assessment. They provide information on brain activity and structure that is invaluable to understanding abnormalities associated with neurodegeneration in PD. Among these tools, functional magnetic resonance imaging (fMRI) is often favored for its safety and spatial resolution. Resting state fMRI research capitalizes on the wealth of information that the brain offers when a person is not performing a motor or cognitive task. It is also a good means to study impaired and heterogeneous populations, such as people with PD. The present article reviews research that applies resting state fMRI to the ongoing hunt for biomarkers of PD non-motor symptoms. Thus far, research in this subfield has focused on two of the most common and significant non-motor symptoms: cognitive impairment and depression. These studies support resting state fMRI as a valid and practical tool for the study of these symptoms, but discrepancies among findings highlight the importance of further research with standardized procedures.

    View details for DOI 10.1186/2054-7072-1-4

    View details for PubMedID 26788330

    View details for PubMedCentralID PMC4677732

  • Functional brain networks and abnormal connectivity in the movement disorders NEUROIMAGE Poston, K. L., Eidelberg, D. 2012; 62 (4): 2261-2270

    Abstract

    Clinical manifestations of movement disorders, such as Parkinson's disease (PD) and dystonia, arise from neurophysiological changes within the cortico-striato-pallidothalamocortical (CSPTC) and cerebello-thalamo-cortical (CbTC) circuits. Neuroimaging techniques that probe connectivity within these circuits can be used to understand how these disorders develop as well as identify potential targets for medical and surgical therapies. Indeed, network analysis of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has identified abnormal metabolic networks associated with the cardinal motor symptoms of PD, such as akinesia and tremor, as well as PD-related cognitive dysfunction. More recent task-based and resting state functional magnetic resonance imaging studies have reproduced several of the altered connectivity patterns identified in these abnormal PD-related networks. A similar network analysis approach in dystonia revealed abnormal disease related metabolic patterns in both manifesting and non-manifesting carriers of dystonia mutations. Other multimodal imaging approaches using magnetic resonance diffusion tensor imaging in patients with primary genetic dystonia suggest abnormal connectivity within the CbTC circuits mediate the clinical manifestations of this inherited neurodevelopmental disorder. Ongoing developments in functional imaging and future studies in early patients are likely to enhance our understanding of these movement disorders and guide novel targets for future therapies.

    View details for DOI 10.1016/j.neuroimage.2011.12.021

    View details for Web of Science ID 000308265200010

    View details for PubMedID 22206967

    View details for PubMedCentralID PMC3489159

  • Network correlates of disease severity in multiple system atrophy NEUROLOGY Poston, K. L., Tang, C. C., Eckert, T., Dhawan, V., Frucht, S., Vonsattel, J., Fahn, S., Eidelberg, D. 2012; 78 (16): 1237-1244

    Abstract

    Multiple system atrophy (MSA), the most common of the atypical parkinsonian disorders, is characterized by the presence of an abnormal spatial covariance pattern in resting state metabolic brain images from patients with this disease. Nonetheless, the potential utility of this pattern as a MSA biomarker is contingent upon its specificity for this disorder and its relationship to clinical disability in individual patients.We used [(18)F]fluorodeoxyglucose PET to study 33 patients with MSA, 20 age- and severity-matched patients with idiopathic Parkinson disease (PD), and 15 healthy volunteers. For each subject, we computed the expression of the previously characterized metabolic covariance patterns for MSA and PD (termed MSARP and PDRP, respectively) on a prospective single-case basis. The resulting network values for the individual patients were correlated with clinical motor ratings and disease duration.In the MSA group, disease-related pattern (MSARP) values were elevated relative to the control and PD groups (p < 0.001 for both comparisons). In this group, MSARP values correlated with clinical ratings of motor disability (r = 0.57, p = 0.0008) and with disease duration (r = -0.376, p = 0.03). By contrast, MSARP expression in the PD group did not differ from control values (p = 1.0). In this group, motor ratings correlated with PDRP (r = 0.60, p = 0.006) but not with MSARP values (p = 0.88).MSA is associated with elevated expression of a specific disease-related metabolic pattern. Moreover, differences in the expression of this pattern in patients with MSA correlate with clinical disability. The findings suggest that the MSARP may be a useful biomarker in trials of new therapies for this disorder.

    View details for DOI 10.1212/WNL.0b013e318250d7fd

    View details for Web of Science ID 000302933200010

    View details for PubMedID 22491861

    View details for PubMedCentralID PMC3324319

  • AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial LANCET NEUROLOGY LeWitt, P. A., Rezai, A. R., Leehey, M. A., Ojemann, S. G., Flaherty, A. W., Eskandar, E. N., Kostyk, S. K., Thomas, K., Sarkar, A., Siddiqui, M. S., Tatter, S. B., Schwalb, J. M., Poston, K. L., Henderson, J. M., Kurlan, R. M., Richard, I. H., Van Meter, L., Sapan, C. V., During, M. J., Kaplitt, M. G., Feigin, A. 2011; 10 (4): 309-319

    Abstract

    Gene transfer of glutamic acid decarboxylase (GAD) and other methods that modulate production of GABA in the subthalamic nucleus improve basal ganglia function in parkinsonism in animal models. We aimed to assess the effect of bilateral delivery of AAV2-GAD in the subthalamic nucleus compared with sham surgery in patients with advanced Parkinson's disease.Patients aged 30-75 years who had progressive levodopa-responsive Parkinson's disease and an overnight off-medication unified Parkinson's disease rating scale (UPDRS) motor score of 25 or more were enrolled into this double-blind, phase 2, randomised controlled trial, which took place at seven centres in the USA between Nov 17, 2008, and May 11, 2010. Infusion failure or catheter tip location beyond a predefined target zone led to exclusion of patients before unmasking for the efficacy analysis. The primary outcome measure was the 6-month change from baseline in double-blind assessment of off-medication UPDRS motor scores. This trial is registered with ClinicalTrials.gov, NCT00643890.Of 66 patients assessed for eligibility, 23 were randomly assigned to sham surgery and 22 to AAV2-GAD infusions; of those, 21 and 16, respectively, were analysed. At the 6-month endpoint, UPDRS score for the AAV2-GAD group decreased by 8·1 points (SD 1·7, 23·1%; p<0·0001) and by 4·7 points in the sham group (1·5, 12·7%; p=0·003). The AAV2-GAD group showed a significantly greater improvement from baseline in UPDRS scores compared with the sham group over the 6-month course of the study (RMANOVA, p=0·04). One serious adverse event occurred within 6 months of surgery; this case of bowel obstruction occurred in the AAV2-GAD group, was not attributed to treatment or the surgical procedure, and fully resolved. Other adverse events were mild or moderate, likely related to surgery and resolved; the most common were headache (seven patients in the AAV2-GAD group vs two in the sham group) and nausea (six vs two).The efficacy and safety of bilateral infusion of AAV2-GAD in the subthalamic nucleus supports its further development for Parkinson's disease and shows the promise for gene therapy for neurological disorders.Neurologix.

    View details for DOI 10.1016/S1474-4422(11)70039-4

    View details for Web of Science ID 000289185000014

    View details for PubMedID 21419704

  • Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) with Myoclonus MOVEMENT DISORDERS Poston, K. L., McGovern, R. A., Goldman, J. S., Caccappolo, E., Mazzoni, P. 2010; 25 (4): 514-516

    View details for DOI 10.1002/mds.22929

    View details for Web of Science ID 000276337400027

    View details for PubMedID 20063436

  • Abnormalities in Metabolic Network Activity Precede the Onset of Motor Symptoms in Parkinson's Disease JOURNAL OF NEUROSCIENCE Tang, C. C., Poston, K. L., Dhawan, V., Eidelberg, D. 2010; 30 (3): 1049-1056

    Abstract

    Imaging studies show that Parkinson's disease (PD) alters the activity of motor- and cognition-related metabolic brain networks. However, it is not known whether the network changes appear at or before symptom onset. In this study, we examined 15 hemiparkinsonian patients who underwent serial metabolic imaging with [(18)F]-fluorodeoxyglucose (FDG) PET at baseline and again 2.1 +/- 0.6 (mean +/- SD) and 3.9 +/- 0.7 years later. We assessed longitudinal changes in network activity in each cerebral hemisphere, focusing specifically on the "presymptomatic" hemisphere--ipsilateral to the initially involved body side. At the network level, the activity of the PD motor-related pattern (PDRP) increased symmetrically in both hemispheres over time (p < 0.001), with significant bilateral elevations at each of the three time points. Hemispheric expression of the PD cognition-related pattern likewise increased symmetrically (p < 0.001), although significant elevations were not evident on either side until 4 years. At the regional level, putamen metabolism contralateral to the initially affected body side was elevated at all three time points, without longitudinal change. In contrast, in the initially presymptomatic hemisphere, putamen metabolic activity increased steadily over time, reaching abnormal levels only at 4 years. Metabolic activity in the contralateral precuneus fell to subnormal levels by the final time point. These findings suggest that abnormal PDRP activity antecedes the appearance of motor signs by approximately 2 years. The timing and laterality of symptom onset relates to focal asymmetric metabolic changes at the putamenal node of this network.

    View details for DOI 10.1523/JNEUROSCI.4188-09.2010

    View details for Web of Science ID 000273779200026

    View details for PubMedID 20089913

    View details for PubMedCentralID PMC2866050

  • FDG PET in the Evaluation of Parkinson's Disease. PET clinics 2010; 5 (1): 55–64

    Abstract

    Network analysis of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is an innovative approach for the study of in movement disorders, such as Parkinson's disease (PD). Spatial covariance analysis of imaging data acquired from PD patients has revealed characteristic regional patterns associated with the motor and cognitive features of disease. Quantification of pattern expression in individual patients can be used for diagnosis, assessment of disease severity, and evaluation of novel medical and surgical therapies. Identification of disease-specific patterns in other parkinsonian syndromes, such as multiple system atrophy and progressive supranuclear palsy, has improved diagnostic accuracy in patients with difficult to diagnose parkinsonism. Further developments of these techniques are likely to enhance the role of functional imaging in investigating underlying abnormalities and potential new therapies in these neurodegenerative diseases.

    View details for DOI 10.1016/j.cpet.2009.12.004

    View details for PubMedID 20689674

    View details for PubMedCentralID PMC2913894

  • Action tremor of the legs in essential tremor: Prevalence, clinical correlates, and comparison with age-matched controls PARKINSONISM & RELATED DISORDERS Poston, K. L., Rios, E., Louis, E. D. 2009; 15 (8): 602-605

    Abstract

    The hallmark feature of essential tremor (ET) is action tremor of the arms. Leg tremor may also occur yet it has not been the central focus of previous studies. Its prevalence has only rarely been reported, its clinical correlates have yet to be explored. Our aims were to report the prevalence and analyze the clinical correlates of leg action tremor in patients with ET and, given the propensity for normal elderly individuals to manifest mild limb tremors, compare the prevalence with that in age-matched controls. Kinetic leg tremor rated > or =1 occurred in 28/63 (44.4%) ET cases and in only 9/63 (14.3%) controls (p<0.001); moderate leg tremor occurred in 14.3% of cases. Leg tremor severity modestly correlated with disease duration (r=0.31, p=0.02). However, the severity and laterality of leg tremor did not correlate with those of arm tremor. The pathophysiological implications of this finding deserve further exploration.

    View details for DOI 10.1016/j.parkreldis.2008.11.006

    View details for Web of Science ID 000270122500011

    View details for PubMedID 19103506

  • Network biomarkers for the diagnosis and treatment of movement disorders NEUROBIOLOGY OF DISEASE Poston, K. L., Eidelberg, D. 2009; 35 (2): 141-147

    Abstract

    Functional brain networks provide a set of useful biomarkers for the assessment of movement disorders such as Parkinson's disease (PD). Spatial covariance analysis of imaging data from PD patients has led to the identification of abnormal metabolic patterns associated with the motor and cognitive features of this disease. Measurements of pattern expression have been used for diagnosis, assessment of rates of disease progression, and objective evaluation of the efficacy of therapeutic interventions. For instance, the recent identification of new disease-specific patterns for Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) has improved diagnostic accuracy in patients with parkinsonian syndromes. Further, disease-related networks have been found to be modulated by novel treatment strategies such as gene therapy. Finally, the application of network analysis to the study of inherited movement disorders such as Huntington's disease can aid in the assessment of disease-modifying therapies in pre-symptomatic gene mutation carriers.

    View details for DOI 10.1016/j.nbd.2008.09.026

    View details for Web of Science ID 000268078300004

    View details for PubMedID 19013242

  • Movement disorder emergencies 16th Symposium on the Treatment of Parkinsons Disease Poston, K. L., Frucht, S. J. SPRINGER HEIDELBERG. 2008: 2–13

    Abstract

    Movement disorder emergencies include any movement disorder which evolves over hours to days, in which failure to appropriately diagnose and manage can result in patient morbidity or mortality. It is crucial that doctors recognize these emergencies with accuracy and speed by obtaining the proper history and by being familiar with the phenomenology of frequently encountered movements. These disorders will be discussed based on the most common associated involuntary movement, either parkinsonism, dystonia, chorea, tics or myoclonus, and, when available, review the workup and treatment options based on the current literature.

    View details for DOI 10.1007/s00415-008-4002-9

    View details for Web of Science ID 000259034000002

    View details for PubMedID 18821080

  • Zydis selegilline in the management of Parkinson's disease EXPERT OPINION ON PHARMACOTHERAPY Poston, K. L., Waters, C. 2007; 8 (15): 2615-2624

    Abstract

    Selegiline, a selective monoamine oxidase-B inhibitor, has been used for decades in the treatment of Parkinson's disease. The recent development of an orally disintegrating dosage form using Zydis technology allows pregastric drug absorption and, thus, greatly improving the pharmacodynamic and pharmacokinetic drug profiles. This new formulation provides higher drug bioavailability and a substantially reduced concentration of active metabolites. As an adjunct to levodopa, Zydis selegiline is shown to be a safe and effective therapy in patients with motor fluctuations and wearing off. This review outlines the advantages of a Zydis formulation in Parkinson's disease and the evidence supporting the use of Zydis selegiline for motor fluctuations.

    View details for DOI 10.1517/14656566.8.15.2615

    View details for Web of Science ID 000250426000014

    View details for PubMedID 17931095