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PLoS One. 2018 Aug 20;13(8):e0201964. doi: 10.1371/journal.pone.0201964. eCollection 2018.

Cognition among individuals along a spectrum of increased risk for Parkinson's disease.

Author information

University of Pittsburgh, Pittsburgh, PA, United States of America.
The University of Iowa, Iowa City, Iowa, United States of America.
Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, England.
Columbia University Medical Center, Department of Neurology, New York, NY, United States of America.
Department of Medicine and Surgery, Center for Neurodegenerative Diseases, University of Salerno, Fisciano, Italy.
Institute for Ageing and Health, Newcastle University, Newcastle, United Kingdom.
Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH, United States of America.
The Michael J. Fox Foundation for Parkinson's Research, New York, NY, United States of America.
Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States of America.
Institute for Neurodegenerative Disorders, New Haven, CT, United States of America.
Cleveland Clinic, Cleveland, OH, United States of America.
UCSD Movement Disorder Center, Department of Neurosciences, University of California San Diego, San Diego, CA, United States of America.
Departments of Neurology and Psychiatry, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States of America.
Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States of America.
Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America.
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, United States of America.
Parkinson's Disease and Mental Illness Research, Education and Clinical Centers (PADRECC and MIRECC), Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, United States of America.



Several characteristics associated with increased risk for Parkinson's disease (PD) have been identified, including specific genotypes and various non-motor symptoms. Characterizing non-motor features, such as cognitive abilities, among individuals considered at-risk for PD is essential to improving prediction of future neurodegeneration.


Participants belonging to the following cohorts of the Parkinson Progression Markers Initiative (PPMI) study were included: de novo PD with dopamine transporter binding deficit (n = 423), idiopathic REM sleep behavior disorder (RBD, n = 39), hyposmia (n = 26) and non-PD mutation carrier (NMC; Leucine-rich repeat kinase 2 (LRRK2) G2019S (n = 88) and glucocerebrosidase (GBA) gene (n = 38) mutations)). Inclusion criteria enriched the RBD and hyposmia cohorts, but not the NMC cohort, with individuals with dopamine transporter binding deficit. Baseline neuropsychological performance was compared, and analyses were adjusted for age, sex, education, and depression.


The RBD cohort performed significantly worse than the hyposmia and NMC cohorts on Symbol Digit Modality Test (mean (SD) 32.4 (9.16) vs. 41.8 (9.98), p = 0.002 and vs. 45.2 (10.9), p<0.001) and Judgment of Line Orientation (11.3 (2.36) vs.12.9 (1.87), p = 0.004 and vs. 12.9 (1.87), p<0.001). The RBD cohort also performed worse than the hyposmia cohort on the Montreal Cognitive Assessment (25.5 (4.13) vs. 27.3 (1.71), p = 0.02). Hyposmics did not differ from PD or NMC cohorts on any cognitive test score.


Among individuals across a spectrum of risk for PD, cognitive function is worse among those with the characteristic most strongly associated with future risk of PD or dementia with Lewy bodies, namely RBD.

[Indexed for MEDLINE]
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Conflict of interest statement

The authors of this paper, who constitute the Cognitive Working Group for the PPMI study, have not received any direct funds for this work. The data used in this study are from the PPMI study. The PPMI study is a public-private partnership funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbvie, Avid, Biogen, Bristol-Myers Squibb, Covance, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeek, Merck, Meso Scale Discovery,Pfizer, Piramal, Roche, Servier, Teva, UCB, and Golub Capital. Lana Chahine: Lana M. Chahine receives research support from the Michael J Fox Foundation, including for the S4 study, has received travel payment from MJFF to MJFF conferences, is a paid consultant to MJFF, receives research support for a clinical trial sponsored by Voyager Therapeutics, received travel payments from Voyager Therapeutics to Investigator meeting, and receives royalties from Wolters Kluwel (for book authorship). Keith Hawkins: NIH/NIA P50 AG047270-01 (PI: Strittmatter; Co-Dir., Clinical Core: Van-Dyck) 6/1/15-5/31/20. Role: Investigator. NIH/NIDA 1R01DA038807-01A1 (PI: G. Pearlson) 8/1/2015-5/31/2020. Role: Investigator. DTNH2216R00036 (PI: Pearlson/Stevens) 10/01/16-9/30/18. Role: Investigator. NIH 1R01AG52560-01A1 (PI: Carson, van Dyck) 09/01/16- 08/31/20. Role: Investigator. Daniel Weintraub: Dr. Weintraub has received research funding or support from Michael J. Fox Foundation for Parkinson’s Research, National Institutes of Health (NINDS), Novartis Pharmaceuticals, Department of Veterans Affairs, Avid Radiopharmaceuticals, Alzheimer’s Disease Cooperative Study, and the International Parkinson and Movement Disorder Society; honoraria for consultancy from Acadia, Biogen, Biotie (Acorda), Bracket, Clintrex LLC, Eisai Inc., Eli Lilly, Lundbeck, Takeda, UCB, and the CHDI Foundation; license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS; royalties from Wolters Kluweland; and fees for legal consultation for lawsuits related to medication prescribing in patients with Parkinson’s disease. Roy Alcalay: Roy Alcalay is funded by the NIH (K02NS080915), Parkinson’s Disease Foundation and the Michael J Fox Foundation. He receives consultation fees from Genzyme/Sanofi, Denali and Prophase. Alberto J. Espay: Dr. Espay has received grant support from the NIH, Great Lakes Neurotechnologies and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, TEVA, Impax, Merz, Acadia, Cynapsus/Sunovion, Lundbeck, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from Abbvie, UCB, USWorldMeds, Lundbeck, Acadia, the American Academy of Neurology, and the Movement Disorders Society. Tanya Simuni: Dr. Simuni has served as a consultant received consulting fees from Acadia, Abbvie, Allergan, Anavex, Avid, GE Medical, Eli Lilly and Company, Harbor, Ibsen, IMPAX, Lundbeck, Merz, Inc., the National Parkinson Foundation, Navidea, Pfizer, TEVA Pharmaceuticals, UCB Pharma, Voyager, US World Meds, and the Michael J. Fox Foundation for Parkinson’s Research; Dr. Simuni has served as a speaker and received an honorarium from Acadia, IMPAX, Lundbeck, TEVA Pharmaceuticals, and UCB Pharma; Dr Simuni is on the Scientific advisory board for Anavex, Sanofi, MJFF. Dr. Simuni sits on the Advisory Board for IMPAX; Dr. Simuni has received research funding from the NINDS, MJFF, NPF, TEVA Pharmaceuticals, Auspex, Biotie, Civitas, Acorda, Lundbeck, Neuroderm, NINDS, National Institutes of Health, Northwestern Foundation, and the Michael J. Fox Foundation for Parkinson’s Research; Dr. Simuni received funding support for educational programs from GE Medical, TEVA, and Lundbeck. Irene Litvan: Dr. Litvan is supported by AVID Pharmaceuticals, C2N Diagnostics/Abbvie and Bristol-Myers Squibb/Biogen, the National Institutes of Health grants: 5P50 AG005131-31, 5T35HL007491, 1U01NS086659, 1U54NS092089-01, and U01NS100610; Parkinson Study Group, Michael J Fox Foundation. She has been a consultant for Toyama. She has been a member of the Biogen, Bristol-Myers Squibb, and Abvie Advisory Boards and is a member of the Biotie/Parkinson Study Group Medical Advisory Board. She receives her salary from the University of California San Diego. James B. Leverenz: Dr. Leverenz receives research support from the Alzheimer’s Disease Association, GE Healthcare, Lewy Body Dementia Association, Michael J Fox Foundation, National Institute of Health, Sanofi/Genzyme. He has served as a consultant for Avid Radiopharmaceuticals, Axovant, Bracco Diagnostics, GE Healthcare, and Takeda Pharmaceuticals. Paolo Barone: Prof. Barone reports personal fees from Acorda, UCB, Zambon, grants from Abbvie, Biotie, Zambon, MJ Fox Foundation. Irene Richard: Grant support from Michael J. Fox Foundation, NIH (NINDS), and the National Parkinson’s Foundation. Shirley Lasch: Shirley Lasch is an employee of Molecular NeuroImaging LCC. Dag Aarsland: Dr. Aarsland has received research support and/or honoraria from Astra-Zeneca, H. Lundbeck, Novartis Pharmaceuticals and GE Health, and serves as paid consultant for H. Lundbeck, Eisai, Heptares, and Axovant. Dag Aarsland is a Royal Society Wolfson Research Merit Award Holder and would like to thank the Wolfson Foundation and the Royal Society for their support. Andrew Siderowf: In the past year, Dr. Siderowf has been employed by Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly and Co. Chelsea Caspell-Garcia: Served as a consultant receiving consulting fees from The Michael J. Fox Foundation for Parkinson’s Research; Received research funding from The Michael J. Fox Foundation for Parkinson’s Research. Christopher S. Coffey: Served as a consultant receiving consulting fees from The Michael J. Fox Foundation for Parkinson’s Research; Received research funding from NINDS, NHLBI, and The Michael J. Fox Foundation for Parkinson’s Research Liz Uribe: Received research funding from NINDS and The Michael J. Fox Foundation for Parkinson’s Research. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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