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Parkinson Disease: HELP
Articles by Maureen A. Leehey
Based on 11 articles published since 2009
(Why 11 articles?)
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Between 2009 and 2019, Maureen Leehey wrote the following 11 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Clinical Trial Association of metabolic syndrome and change in Unified Parkinson's Disease Rating Scale scores. 2017

Leehey, Maureen / Luo, Sheng / Sharma, Saloni / Wills, Anne-Marie A / Bainbridge, Jacquelyn L / Wong, Pei Shieen / Simon, David K / Schneider, Jay / Zhang, Yunxi / Pérez, Adriana / Dhall, Rohit / Christine, Chadwick W / Singer, Carlos / Cambi, Franca / Boyd, James T. ·From the Department of Neurology (M.L.) and Department of Clinical Pharmacy (J.L.B.), Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora · Department of Biostatistics (S.L., Y.Z.), University of Texas Health Science Center at Houston · Center for Human Experimental Therapeutics (S.S.), University of Rochester, NY · Department of Neurology (A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston · Department of Pharmacy (P.S.W.), Singapore General Hospital · Department of Neurology (D.K.S.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA · Department of Pathology, Anatomy, & Cell Biology (J.S.), Thomas Jefferson University, Philadelphia, PA · Department of Biostatistics (Y.Z.), School of Public Health, University of Texas Health Science Center, Houston · Department of Biostatistics (A.P.), School of Public Health, University of Texas Health Science Center at Houston-UTHealth, Austin · Department of Neurology (R.D.), University of Arkansas for Medical Sciences, Little Rock · Department of Neurology (C.W.C.), University of California San Francisco · Department of Neurology (C.S.), Leonard M. Miller School of Medicine, University of Miami, FL · Department of Neurology (F.C.), University of Pittsburgh, PA · and Department of Neurological Sciences (J.T.B.), Larner College of Medicine, University of Vermont, Burlington. Dr. Luo is currently with the Department of Biostatistics and Bioinformatics, Duke University, Durham, NC. ·Neurology · Pubmed #28972194.

ABSTRACT: OBJECTIVE: To explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT). METHODS: This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome. RESULTS: Participants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; CONCLUSIONS: Persons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding. CLINICALTRIALSGOV IDENTIFIER: NCT00449865.

2 Clinical Trial Long-term follow-up of a randomized AAV2- 2017

Niethammer, Martin / Tang, Chris C / LeWitt, Peter A / Rezai, Ali R / Leehey, Maureen A / Ojemann, Steven G / Flaherty, Alice W / Eskandar, Emad N / Kostyk, Sandra K / Sarkar, Atom / Siddiqui, Mustafa S / Tatter, Stephen B / Schwalb, Jason M / Poston, Kathleen L / Henderson, Jaimie M / Kurlan, Roger M / Richard, Irene H / Sapan, Christine V / Eidelberg, David / During, Matthew J / Kaplitt, Michael G / Feigin, Andrew. ·Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, USA. · Parkinson's Disease and Movement Disorders Program, Henry Ford Hospital, West Bloomfield, Michigan, USA; Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA. · Department of Neurological Surgery, The Ohio State University College of Medicine, Columbus, Ohio, USA. · Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA. · Department of Neurology and. · Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts, USA. · Department of Neurosurgery, Geisinger Health System, Danville, Pennsylvania, USA. · Department of Neurology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. · Movement Disorder & Comprehensive Epilepsy Centers, Henry Ford Medical Group, West Bloomfield, Michigan, USA. · Department of Neurology and Neurological Sciences and. · Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA. · Neurology, The Center for Neurological and Neurodevelopmental Health, Voorhees, New Jersey, USA. · Department of Neurology and Department of Psychiatry, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA. · Asana Medical Inc., Miami Lakes, Florida, USA. · Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University College of Medicine, Columbus, Ohio, USA. · Department of Neurological Surgery, Weill Cornell Medical College, New York, New York, USA. ·JCI Insight · Pubmed #28405611.

ABSTRACT:

3 Clinical Trial Choice of dopaminergic therapy among early, mild Parkinson disease subjects in North America. 2016

Goudreau, John L / Pérez, Adriana / Aminoff, Michael J / Boyd, James T / Burau, Keith D / Christine, Chadwick W / Leehey, Maureen / Morgan, John C / Anonymous1440871. ·Department of Neurology, Michigan State University, 804 Service Rd Room A217, East Lansing, MI 48824, USA. Electronic address: john.goudreau@hc.msu.edu. · Department of Biostatistics, The University of Texas Health Science Center at Houston, UTHealth, USA. Electronic address: adriana.perez@uth.tmc.edu. · Department of Neurology, University of California San Francisco, 505 Parnassus Ave, Moffitt, San Francisco, CA 94143, USA. Electronic address: Michael.Aminoff@ucsf.edu. · Department of Neurological Sciences, University of Vermont, College of Medicine, 1 So. Prospect Street, UHC - Arnold 2, Burlington, VT 05401, USA. Electronic address: James.Boyd@uvm.edu. · Department of Biostatistics, The University of Texas Health Science Center at Houston, UTHealth, USA. Electronic address: kb_athome@yahoo.com. · Department of Neurology, University of California San Francisco, 505 Parnassus Ave, Moffitt, San Francisco, CA 94143, USA. Electronic address: chad.christine@ucsf.edu. · Department of Neurology, University of Colorado, School of Medicine, Academic Office 1, Mail Stop B-185, 12631 East 17th Avenue, Aurora, CO 80045, USA. Electronic address: maureen.leehey@ucdenver.edu. · Department of Neurology, Georgia Regent's University, 1120 15th St, Augusta, GA 30912, USA. Electronic address: jmorgan@gru.edu. ·J Neurol Sci · Pubmed #27288780.

ABSTRACT: The choice of dopaminergic therapy in early Parkinson disease (PD) is an important clinical decision, yet factors influencing this decision have not been extensively studied. We sought to investigate the factors that may be associated with the choice of dopaminergic therapy at the NINDS Exploratory Trials in PD (NET-PD) Long-Term Study-1 (LS1). NET-PD LS1 was a clinical trial of creatine versus placebo in participants with early, mild PD on stable doses of dopaminergic therapy. Baseline data from 1616 out of the 1741 participants were evaluated using univariable and multivariable logistic or generalized logit regression analyses for available factors associated with the choice of dopaminergic therapy. The dopaminergic therapy choice was determined as: (i) therapy that subjects recalled taking 180days before the study; (ii) therapy at baseline; and (iii) the longest duration of therapy reported by participants. Younger age, higher education level, longer length of time since PD diagnosis and use of an adjunctive, non-dopaminergic or monoamine oxidase inhibitor medication were associated with more frequent use of dopamine agonist compared to levodopa or combination therapy.

4 Clinical Trial A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. 2014

Anonymous1090789 / Beal, M Flint / Oakes, David / Shoulson, Ira / Henchcliffe, Claire / Galpern, Wendy R / Haas, Richard / Juncos, Jorge L / Nutt, John G / Voss, Tiffini Smith / Ravina, Bernard / Shults, Clifford M / Helles, Karen / Snively, Victoria / Lew, Mark F / Griebner, Brian / Watts, Arthur / Gao, Shan / Pourcher, Emmanuelle / Bond, Louisette / Kompoliti, Katie / Agarwal, Pinky / Sia, Cherissa / Jog, Mandar / Cole, Linda / Sultana, Munira / Kurlan, Roger / Richard, Irene / Deeley, Cheryl / Waters, Cheryl H / Figueroa, Angel / Arkun, Ani / Brodsky, Matthew / Ondo, William G / Hunter, Christine B / Jimenez-Shahed, Joohi / Palao, Alicia / Miyasaki, Janis M / So, Julie / Tetrud, James / Reys, Liza / Smith, Katharine / Singer, Carlos / Blenke, Anita / Russell, David S / Cotto, Candace / Friedman, Joseph H / Lannon, Margaret / Zhang, Lin / Drasby, Edward / Kumar, Rajeev / Subramanian, Thyagarajan / Ford, Donna Stuppy / Grimes, David A / Cote, Diane / Conway, Jennifer / Siderowf, Andrew D / Evatt, Marian Leslie / Sommerfeld, Barbara / Lieberman, Abraham N / Okun, Michael S / Rodriguez, Ramon L / Merritt, Stacy / Swartz, Camille Louise / Martin, W R Wayne / King, Pamela / Stover, Natividad / Guthrie, Stephanie / Watts, Ray L / Ahmed, Anwar / Fernandez, Hubert H / Winters, Adrienna / Mari, Zoltan / Dawson, Ted M / Dunlop, Becky / Feigin, Andrew S / Shannon, Barbara / Nirenberg, Melissa Jill / Ogg, Mattson / Ellias, Samuel A / Thomas, Cathi-Ann / Frei, Karen / Bodis-Wollner, Ivan / Glazman, Sofya / Mayer, Thomas / Hauser, Robert A / Pahwa, Rajesh / Langhammer, April / Ranawaya, Ranjit / Derwent, Lorelei / Sethi, Kapil D / Farrow, Buff / Prakash, Rajan / Litvan, Irene / Robinson, Annette / Sahay, Alok / Gartner, Maureen / Hinson, Vanessa K / Markind, Samuel / Pelikan, Melisa / Perlmutter, Joel S / Hartlein, Johanna / Molho, Eric / Evans, Sharon / Adler, Charles H / Duffy, Amy / Lind, Marlene / Elmer, Lawrence / Davis, Kathy / Spears, Julia / Wilson, Stephanie / Leehey, Maureen A / Hermanowicz, Neal / Niswonger, Shari / Shill, Holly A / Obradov, Sanja / Rajput, Alex / Cowper, Marilyn / Lessig, Stephanie / Song, David / Fontaine, Deborah / Zadikoff, Cindy / Williams, Karen / Blindauer, Karen A / Bergholte, Jo / Propsom, Clara Schindler / Stacy, Mark A / Field, Joanne / Mihaila, Dragos / Chilton, Mark / Uc, Ergun Y / Sieren, Jeri / Simon, David K / Kraics, Lauren / Silver, Althea / Boyd, James T / Hamill, Robert W / Ingvoldstad, Christopher / Young, Jennifer / Thomas, Karen / Kostyk, Sandra K / Wojcieszek, Joanne / Pfeiffer, Ronald F / Panisset, Michel / Beland, Monica / Reich, Stephen G / Cines, Michelle / Zappala, Nancy / Rivest, Jean / Zweig, Richard / Lumina, L Pepper / Hilliard, Colette Lynn / Grill, Stephen / Kellermann, Marye / Tuite, Paul / Rolandelli, Susan / Kang, Un Jung / Young, Joan / Rao, Jayaraman / Cook, Maureen M / Severt, Lawrence / Boyar, Karyn. ·Department of Neurology, Weill Cornell Medical College, New York Hospital, New York. · Department of Biostatistics, University of Rochester Medical Center, Rochester, New York. · Department of Neurology, Georgetown University, Washington, DC. · National Institutes of Health, Bethesda, Maryland. · Department of Neurosciences, University of California, San Diego, La Jolla. · Department of Neurology, Emory University School of Medicine, Wesley Woods Center, Atlanta, Georgia. · Department of Neurology, Oregon Health and Science University, Portland. · Merck, New Jersey. · Biogen Idec, Cambridge, Massachusetts. · Department of Neurosciences, University of California, San Diego, La Jolla10VA Medical Center, San Diego, California. · Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles. · Department of Biostatistics, University of Rochester Medical Center, Rochester, New York12Department of Neurology, University of Rochester, Rochester, New York. · Québec Memory and Motor Skills Disorders Research Center, Clinique Sainte-Anne, Québec, Canada. · Rush University Medical Center, Chicago, Illinois. · Booth Gardner Parkinson's Care Center, EvergreenHealth, Kirkland, Washington. · London Health Sciences Centre, London, Ontario, Canada. · Overlook Medical Center, Atlantic Neuroscience Institute, Summit, New Jersey. · Department of Neurology, University of Rochester, Rochester, New York. · Columbia University Medical Center, Neurological Institute, New York, New York. · Department of Neurology, University of Texas Health Science Center at Houston. · Department of Neurology, Baylor College of Medicine, Houston, Texas. · Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. · The Parkinson's Institute and Clinical Center, Sunnyvale, California. · Department of Neurology, University of Miami School of Medicine, Miami, Florida. · Institute for Neurodegenerative Disorders, New Haven, Connecticut. · Department of Neurology, Butler Hospital, Providence, Rhode Island26Alpert Medical School, Brown University, Providence, Rhode Island. · Department of Neurology, Butler Hospital, Providence, Rhode Island27Port City Neurology, Inc, Scarborough, Maine. · Department of Neurology, University of California, Davis, School of Medicine and Sacramento VA Medical Center, Sacramento. · Port City Neurology, Inc, Scarborough, Maine. · Colorado Neurological Institute, Englewood. · Milton S. Hershey Medical Center, Department of Neurology, Pennsylvania State Hershey College of Medicine, Hershey. · Ottawa Hospital Civic Site, Ottawa, Ontario, Canada. · Avid Radiopharmaceuticals, Philadelphia, Pennsylvania. · Department of Neurology, Emory University School of Medicine, Wesley Woods Center, Atlanta, Georgia33Atlanta VA Medical Center, Atlanta, Georgia. · Muhammad Ali Parkinson Center, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, Arizona. · Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville. · Glenrose Rehabilitation Hospital, University of Alberta, Edmonton, Alberta, Canada. · Department of Neurology, University of Alabama at Birmingham. · Center for Neurological Restoration, Department of Neurology, Cleveland Clinic, Cleveland, Ohio. · Department of Neurology, Johns Hopkins University, Baltimore, Maryland. · Feinstein Institute for Medical Research, Center for Neurosciences, Manhasset, New York. · Department of Neurology, New York University Langone Medical Center, New York. · Department of Neurology, Boston University School of Medicine, Boston, Massachusetts. · The Parkinson's and Movement Disorder Institute, Fountain Valley, California. · State University of New York, Downstate Medical Center, Brooklyn, New York. · Department of Neurology, University of South Florida, Tampa. · Department of Neurology, University of Kansas Medical Center, Kansas City. · Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. · Department of Neurology, Georgia Health Science University, Augusta. · Department of Neurology, University of Louisville, Kentucky. · University of Cincinnati College of Medicine, Cincinnati, Ohio. · Department of Neurology, Medical University of South Carolina, Charleston. · Associated Neurologists, PC, Danbury, Connecticut. · Department of Neurology, Washington University in St Louis, Missouri. · Movement Disorders Center, Albany Medical Center, Albany, New York. · Parkinson's Disease and Movement Disorders Center, Department of Neurology, Mayo Clinic, Scottsdale, Arizona. · Center for Neurological Health, University of Toledo, Toledo, Ohio. · Department of Neurology, Medical University of Ohio at Toledo. · Department of Neurology, University of Colorado Health Science Center, Denver. · Department of Neurology, University of California, Irvine Medical Center, Irvine. · Banner Sun Health Research Institute, Sun City, Arizona. · Department of Neurology, University of Saskatchewan, Royal University Hospital, Saskatchewan, Canada. · Department of Neurology, University of California, San Diego, La Jolla. · Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Department of Neurology, Medical College of Wisconsin, Milwaukee. · Department of Neurology, Duke University, Durham, North Carolina. · State University of New York Upstate Medical Center and Syracuse VA Medical Center, Syracuse. · Department of Neurology, University of Iowa, Iowa City. · Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts. · Department of Neurology, University of Vermont College of Medicine, Burlington. · Department of Neurology, Ohio State University, Columbus. · Department of Neurology, Indiana University School of Medicine, Indianapolis. · Department of Neurology, University of Tennessee Health Science Center, Memphis. · Department of Neurology, CHUM-Hôpital Notre-Dame, Montréal, Québec, Canada. · Department of Neurology, University of Maryland School of Science, Baltimore. · Department of Neurology, University of Sherbrooke, Québec, Canada. · Department of Neurology, Louisiana State University Health Science Center, Shreveport. · Lewis Hall Singletary Oncology Center, Thomasville, Georgia. · Parkinson and Movement Disorders Center of Maryland, Elkridge. · Department of Neurology, University of Minnesota, Minneapolis. · Department of Neurology, University of Chicago, Chicago, Illinois. · Department of Neurology, Ochsner Clinic Foundation, New Orleans, Louisiana. · Department of Neurology, Beth Israel Medical Center, New York, New York. ·JAMA Neurol · Pubmed #24664227.

ABSTRACT: IMPORTANCE: Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. OBJECTIVE: To examine whether CoQ10 could slow disease progression in early PD. DESIGN, SETTING, AND PARTICIPANTS: A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. INTERVENTIONS: The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. MAIN OUTCOMES AND MEASURES: Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. RESULTS: The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). CONCLUSIONS AND RELEVANCE: Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00740714.

5 Article Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson's Disease: An Analysis of NET-PD LS1. 2017

Hauser, Robert A / Li, Ruosha / Pérez, Adriana / Ren, Xuehan / Weintraub, Dan / Elm, Jordan / Goudreau, John L / Morgan, John C / Fang, John Y / Aminoff, Michael J / Christine, Chadwick W / Dhall, Rohit / Umeh, Chizoba C / Boyd, James T / Stover, Natividad / Leehey, Maureen / Zweig, Richard M / Nicholas, Anthony P / Bodis-Wollner, Ivan / Willis, Allison / Kieburtz, Karl / Tilley, Barbara C / Anonymous4700889. ·Departments of Neurology, Molecular Pharmacology and Physiology, University of South Florida, Parkinson's Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, Tampa FL, USA. · Department of Biostatistics, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, TX, USA. · Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. · Medical University of South Carolina, Department of Public Health Sciences, Charleston, SC, USA. · Department of Neurology, Michigan State University, East Lansing, MI, USA. · National Parkinson Foundation Center of Excellence, Movement Disorders Program, Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, USA. · Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA. · University of California, San Francisco, Department of Neurology, University of California, San Francisco, CA, USA. · The Parkinson's Institute and Clinical Center, Sunnyvale, CA, USA. · Division of Movement Disorders, Brigham and Women's Hospital, Boston, MA, USA. · Department of Neurological Sciences, University of Vermont, College of Medicine, Burlington, VT, USA. · Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, USA. · Department of Neurology, University of Colorado, School of Medicine, Aurora, CO, USA. · Department of Neurology, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA. · Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA. · Departments of Neurology and Ophthalmology, Parkinson's Disease and Related Disorders Clinic, Center of Excellence, State University of New York, Downstate Medical Center, Brooklyn, NY, USA. · Department of Neurology, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA. · University of Rochester, Center for Human Experimental Therapeutics, Rochester, NY, USA. ·J Parkinsons Dis · Pubmed #27911341.

ABSTRACT: BACKGROUND: Monoamine oxidase type B (MAO-B) inhibitors exhibit neuroprotective effects in preclinical models of PD but clinical trials have failed to convincingly demonstrate disease modifying benefits in PD patients. OBJECTIVE: To perform a secondary analysis of NET-PD LS1 to determine if longer duration of MAO-B inhibitor exposure was associated with less clinical decline. METHODS: The primary outcome measure was the Global Outcome (GO), comprised of 5 measures: change from baseline in the Schwab and England (ADL) scale, the 39-item Parkinson's Disease Questionnaire (PDQ-39), the UPDRS Ambulatory Capacity Scale, the Symbol Digit Modalities Test, and the most recent Modified Rankin Scale. A linear mixed model was used to explore the association between the cumulative duration of MAO-B inhibitor exposure and the GO, adjusting for necessary factors and confounders. Associations between MAO-B inhibitor exposure and each of the five GO components were then studied individually. RESULTS: 1616 participants comprised the analytic sample. Mean observation was 4.1 (SD = 1.4) years, and 784 (48.5%) participants received an MAO-B inhibitor. The regression coefficient of cumulative duration of MAO-B inhibitor exposure (in years) on the GO was - 0.0064 (SE = 0.002, p = 0.001). Significant associations between duration of MAO-B inhibitor exposure and less progression were observed for ADL (p < 0.001), Ambulatory Capacity (p < 0.001), and the Rankin (p = 0.002). CONCLUSIONS: Our analysis identified a significant association between longer duration of MAO-B inhibitor exposure and less clinical decline. These findings support the possibility that MAO-B inhibitors slow clinical disease progression and suggest that a definitive prospective trial should be considered.

6 Article Levodopa modulates small-world architecture of functional brain networks in Parkinson's disease. 2016

Berman, Brian D / Smucny, Jason / Wylie, Korey P / Shelton, Erika / Kronberg, Eugene / Leehey, Maureen / Tregellas, Jason R. ·Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. · Neurology Section, Denver VA Medical Center, Denver, Colorado, USA. · Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. · Research Service, Denver VA Medical Center, Denver, Colorado, USA. ·Mov Disord · Pubmed #27461405.

ABSTRACT: BACKGROUND: PD is associated with disrupted connectivity to a large number of distributed brain regions. How the disease alters the functional topological organization of the brain, however, remains poorly understood. Furthermore, how levodopa modulates network topology in PD is largely unknown. The objective of this study was to use resting-state functional MRI and graph theory to determine how small-world architecture is altered in PD and affected by levodopa administration. METHODS: Twenty-one PD patients and 20 controls underwent functional MRI scanning. PD patients were scanned off medication and 1 hour after 200 mg levodopa. Imaging data were analyzed using 226 nodes comprising 10 intrinsic brain networks. Correlation matrices were generated for each subject and converted into cost-thresholded, binarized adjacency matrices. Cost-integrated whole-brain global and local efficiencies were compared across groups and tested for relationships with disease duration and severity. RESULTS: Data from 2 patients and 4 controls were excluded because of excess motion. Patients off medication showed no significant changes in global efficiency and overall local efficiency, but in a subnetwork analysis did show increased local efficiency in executive (P = 0.006) and salience (P = 0.018) networks. Levodopa significantly decreased local efficiency (P = 0.039) in patients except within the subcortical network, in which it significantly increased local efficiency (P = 0.007). CONCLUSIONS: Levodopa modulates global and local efficiency measures of small-world topology in PD, suggesting that degeneration of nigrostriatal neurons in PD may be associated with a large-scale network reorganization and that levodopa tends to normalize the disrupted network topology in PD. © 2016 International Parkinson and Movement Disorder Society.

7 Article Association Between Change in Body Mass Index, Unified Parkinson's Disease Rating Scale Scores, and Survival Among Persons With Parkinson Disease: Secondary Analysis of Longitudinal Data From NINDS Exploratory Trials in Parkinson Disease Long-term Study 1. 2016

Wills, Anne-Marie A / Pérez, Adriana / Wang, Jue / Su, Xiao / Morgan, John / Rajan, Suja S / Leehey, Maureen A / Pontone, Gregory M / Chou, Kelvin L / Umeh, Chizoba / Mari, Zoltan / Boyd, James / Anonymous3950854. ·Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston. · Department of Biostatistics, The University of Texas Health Science Center at Houston UTHealth, School of Public Health, Austin. · UTHealth, The University of Texas School of Public Health, Houston. · Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta. · Department of Management, Policy and Community Health, The University of Texas Health Science Center at Houston UTHealth, School of Public Health, Houston. · Department of Neurology, University of Colorado Hospital and University of Colorado School of Medicine, Aurora. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland. · Departments of Neurology and Neurosurgery, University of Michigan, Ann Arbor. · Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Neurology, Johns Hopkins University, Baltimore, Maryland. · Department of Neurological Sciences, University of Vermont College of Medicine, Burlington. ·JAMA Neurol · Pubmed #26751506.

ABSTRACT: IMPORTANCE: Greater body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) is associated with improved survival among persons with Huntington disease or amyotrophic lateral sclerosis. Weight loss is common among persons with Parkinson disease (PD) and is associated with worse quality of life. OBJECTIVE: To explore the association between change in BMI, Unified Parkinson's Disease Rating Scale (UPDRS) motor and total scores, and survival among persons with PD and to test whether there is a positive association between BMI at randomization and survival. DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis (from May 27, 2014, to October 13, 2015) of longitudinal data (3-6 years) from 1673 participants who started the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1). This was a double-blind randomized placebo-controlled clinical trial of creatine monohydrate (10 g/d) that was performed at 45 sites throughout the United States and Canada. Participants with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) PD were enrolled from March 2007 to May 2010 and followed up until September 2013. MAIN OUTCOMES AND MEASURES: Change across time in motor UPDRS score, change across time in total UPDRS score, and time to death. Generalized linear mixed models were used to estimate the effect of BMI on the change in motor and total UPDRS scores after controlling for covariates. Survival was analyzed using Cox proportional hazards models of time to death. A participant's BMI was measured at randomization, and BMI trajectory groups were classified according to whether participants experienced weight loss ("decreasing BMI"), weight stability ("stable BMI"), or weight gain ("increasing BMI") during the study. RESULTS: Of the 1673 participants (mean [SD] age, 61.7 [9.6] years; 1074 [64.2%] were male), 158 (9.4%) experienced weight loss (decreasing BMI), whereas 233 (13.9%) experienced weight gain (increasing BMI). After adjusting for covariates, we found that the weight-loss group's mean (SE) motor UPDRS score increased by 1.48 (0.28) (P < .001) more points per visit than the weight-stable group's mean (SE) motor UPDRS score. The weight-gain group's mean (SE) motor UPDRS score decreased by -0.51 (0.24) (P = .03) points per visit, relative to the weight-stable group. While there was an unadjusted difference in survival between the 3 BMI trajectory groups (log-rank P < .001), this was not significant after adjusting for covariates. CONCLUSIONS AND RELEVANCE: Change in BMI was inversely associated with change in motor and total UPDRS scores in the NET-PD LS-1. Change in BMI was not associated with survival; however, these results were limited by the low number of deaths in the NET-PD LS-1. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00449865.

8 Article Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. 2015

Anonymous2041224 / Kieburtz, Karl / Tilley, Barbara C / Elm, Jordan J / Babcock, Debra / Hauser, Robert / Ross, G Webster / Augustine, Alicia H / Augustine, Erika U / Aminoff, Michael J / Bodis-Wollner, Ivan G / Boyd, James / Cambi, Franca / Chou, Kelvin / Christine, Chadwick W / Cines, Michelle / Dahodwala, Nabila / Derwent, Lorelei / Dewey, Richard B / Hawthorne, Katherine / Houghton, David J / Kamp, Cornelia / Leehey, Maureen / Lew, Mark F / Liang, Grace S Lin / Luo, Sheng T / Mari, Zoltan / Morgan, John C / Parashos, Sotirios / Pérez, Adriana / Petrovitch, Helen / Rajan, Suja / Reichwein, Sue / Roth, Jessie Tatsuno / Schneider, Jay S / Shannon, Kathleen M / Simon, David K / Simuni, Tanya / Singer, Carlos / Sudarsky, Lewis / Tanner, Caroline M / Umeh, Chizoba C / Williams, Karen / Wills, Anne-Marie. ·University of Rochester, Rochester, New York. · University of Texas Health Science Center at Houston. · Medical University of South Carolina, Charleston. · National Institutes of Health, Bethesda, Maryland. · University of South Florida, Tampa. · Pacific Health Research and Education Institute, Honolulu, Hawaii. · University of California, San Francisco. · State University of New York Downstate Medical Center, Brooklyn. · University of Vermont, Burlington. · University of Kentucky, Lexington. · University of Michigan, Ann Arbor. · University of Maryland School of Medicine, Baltimore. · University of Pennsylvania, Philadelphia. · University of Calgary, Calgary, Alberta, Canada. · University of Texas Southwestern Medical Center, Dallas. · University of Southern California, Los Angeles. · Ochsner Medical Center, New Orleans, Louisiana. · University of Colorado Denver, Aurora. · The Parkinson's Institute and Clinical Center, Sunnyvale, California. · Johns Hopkins University, Baltimore, Maryland. · Georgia Regents University, Augusta. · Struthers Parkinson's Center, Golden Valley, Minnesota. · Thomas Jefferson University, Philadelphia, Pennsylvania. · Rush University Medical Center, Chicago, Illinois. · Beth Israel Deaconess Medical Center, Boston, Massachusetts. · Northwestern University, Chicago, Illinois. · University of Miami, Miami, Florida. · Brigham and Women's Hospital, Boston, Massachusetts. ·JAMA · Pubmed #25668262.

ABSTRACT: IMPORTANCE: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. OBJECTIVE: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. DESIGN, SETTING, AND PATIENTS: The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. INTERVENTIONS: Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). MAIN OUTCOMES AND MEASURES: The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. RESULTS: The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. CONCLUSIONS AND RELEVANCE: Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00449865.

9 Article Parkinson's disease severity and use of dopaminergic medications. 2015

Fang, John Y / Pérez, Adriana / Christine, Chadwick W / Leehey, Maureen / Aminoff, Michael J / Boyd, James T / Morgan, John C / Dhall, Rohit / Nicholas, Anthony P / Bodis-Wollner, Ivan / Zweig, Richard M / Goudreau, John L / Anonymous2560816. ·Department of Neurology, Vanderbilt University, 1161 21st Ave South, A-0118, Nashville, TN 37232, USA. Electronic address: john.y.fang@vanderbilt.edu. · UTHealth, The University of Texas School of Public Health, Austin Regional Campus, University of Texas Administration Building (UTA), 1616 Guadalupe Street, Suite 6.300, Austin, TX 78701, USA. · Department of Neurology, University of California at San Francisco, 400 Parnassus Ave, Box 0348, San Francisco, CA 94143, USA. · Department of Neurology, University of Colorado School of Medicine, Academic Office 1, Mail Stop B-185, 12631 East 17th Avenue, Aurora, CO 80045, USA. · Department of Neurology, School of Medicine, University of California at San Francisco, 505 Parnassus Ave, Box 0114, San Francisco, CA 94143-0114, USA. · Department of Neurological Sciences, University of Vermont College of Medicine, 1 South Prospect Street, Burlington, VT 05401, USA. · Movement and Cognitive Disorders Center, Department of Neurology, Medical College of Georgia, Georgia Regents University, 1429 Harper Street, HF-1154, Augusta, GA 30912, USA. · Barrow Neurological Institute, 240 W Thomas Road, Suite 301, Phoenix, AZ 85013, USA. · Department of Neurology, University of Alabama at Birmingham and The Birmingham VA Medical Center, 1720 2nd Avenue South, Birmingham, AL 35294, USA. · Department of Neurology, State University of New York, Downstate Medical Center, 450 Clarkson Ave, Brooklyn, NY 11203, USA; Department of Ophthalmology, State University of New York, Downstate Medical Center, 450 Clarkson Ave, Brooklyn, NY 11203, USA. · Department of Neurology, LSU Health Sciences Center in Shreveport, 1501 King's Highway, Shreveport, LA 71130, USA. · Department of Neurology, Michigan State University, 804 Service Rd, Room A217, USA. ·Parkinsonism Relat Disord · Pubmed #25541182.

ABSTRACT: BACKGROUND: The effects of dopaminergic therapy in parkinson's disease (PD) can vary depending on the class of medication selected. OBJECTIVE: The aim of this post hoc study was to determine if the class of dopaminergic therapy correlated with disease severity in persons with early, treated PD. METHODS: A non-parametric global statistical test (GST) was used to assess the status of participants treated with dopamine agonist (DA) monotherapy, levodopa (LD) monotherapy or combined LD and DA therapy on multiple PD outcomes encompassing motor, cognitive, psychiatric and autonomic function, as well as disability and quality of life. RESULTS: The outcomes measured at the beginning of the study showed lower disease burden for participants on initial DA monotherapy compared to those taking combined LD and DA therapy after controlling for age, education, taking cog-meds and amantadine. CONCLUSION: This observation suggests that clinicians treating early PD patients favor combined LD and DA therapy in patients with more disabling features over DA monotherapy. As such, studies of PD progression in treated PD patients may be affected by the class of symptomatic dopaminergic therapy.

10 Article FMR1 gray-zone alleles: association with Parkinson's disease in women? 2011

Hall, Deborah A / Berry-Kravis, Elizabeth / Zhang, Wenting / Tassone, Flora / Spector, Elaine / Zerbe, Gary / Hagerman, Paul J / Ouyang, Bichun / Leehey, Maureen A. ·Department of Neurological Sciences, Rush University, 1725 West Harrison St., Suite 755, Chicago, IL 60611, USA. Deborah_A_Hall@rush.edu ·Mov Disord · Pubmed #21567456.

ABSTRACT: Carriers of fragile X mental retardation 1 repeat expansions in the premutation range (55-200 CGG repeats), especially males, often develop tremor, ataxia, and parkinsonism. These neurological signs are believed to be a result of elevated levels of expanded CGG-repeat fragile X mental retardation 1 mRNA. The purpose of this study was to determine the prevalence of fragile X mental retardation 1 repeat expansions in a movement disorder population comprising subjects with all types of tremor, ataxia, and parkinsonism. We screened 335 consecutive patients with tremor, ataxia, or parkinsonism and 273 controls confirmed to have no movement disorders. There was no difference in fragile X mental retardation 1 premutation size expansions in the cases compared with controls. Eleven percent of the women with Parkinson's disease had fragile X mental retardation 1 gray-zone expansions compared with 4.4% of female controls (odds ratio of 3.2; 95% confidence interval, 1.2-8.7). Gray-zone expansions in patients with other phenotypes were not overrepresented in comparison with controls. Fragile X mental retardation 1 premutation range expansions are not more common in a mixed movement disorder population compared with controls. Our results, however, suggest that fragile X mental retardation 1 gray-zone alleles may be associated with Parkinson's disease in women.

11 Article AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial. 2011

LeWitt, Peter A / Rezai, Ali R / Leehey, Maureen A / Ojemann, Steven G / Flaherty, Alice W / Eskandar, Emad N / Kostyk, Sandra K / Thomas, Karen / Sarkar, Atom / Siddiqui, Mustafa S / Tatter, Stephen B / Schwalb, Jason M / Poston, Kathleen L / Henderson, Jaimie M / Kurlan, Roger M / Richard, Irene H / Van Meter, Lori / Sapan, Christine V / During, Matthew J / Kaplitt, Michael G / Feigin, Andrew. ·Wayne State University School of Medicine, Parkinson's Disease and Movement Disorders Program, Henry Ford West Bloomfield Hospital, MI, USA. ·Lancet Neurol · Pubmed #21419704.

ABSTRACT: BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Neurologix.