@article{00c190fd43f3461ea34e23d603a0b16c,
title = "Apathy and Anxiety in De Novo Parkinson's Disease Predict the Severity of Motor Complications",
abstract = "Background: Neuropsychiatric and affective symptoms are prevalent in prodromal and clinical Parkinson's disease (PD). Some evidence suggests that they may also signify risk for motor complications (motor fluctuations and dyskinesias) of dopamine replacement therapy (DRT). Objective: To determine whether neuropsychiatric symptoms present in de novo PD (ie, before DRT initiation) predict the severity of eventual motor complications of DRT. Methods: We used clinical, demographic, neurobehavioral, and neuroimaging data from the Parkinson's Progression Markers Initiative (PPMI), a multicenter observational PD study. Participants were unmedicated at enrollment and 361 initiated DRT during PPMI follow-up. We used Cox proportional hazard and multivariate ordinal mixed-effects regression models to evaluate the relationship between baseline neuropsychiatric symptoms and motor complications as measured by the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Results: The cumulative incidences of dyskinesias and motor fluctuations during follow-up (6.0 ± 1.5 years) were 34.3% and 59.9%, respectively. Both apathy and high trait-anxiety (top quartile) conveyed over two-fold increases in hazard for dyskinesia onset and for adverse impact on activities of daily living caused by both dyskinesias and motor fluctuations. The longitudinal severity of motor fluctuations and dyskinesias was significantly predicted by baseline trait-anxiety and apathy, but not depression. Models were adjusted for dimensionally related symptoms (eg autonomic dysfunction) and potential confounding variables (eg DRT dose). Conclusions: Apathy and anxiety levels in de novo PD may be neuropsychiatric biomarkers of vulnerability to earlier and more disabling motor complications of DRT.",
keywords = "Parkinson's disease, anxiety, apathy, dyskinesias, fluctuations",
author = "Hinkle, {Jared T.} and Kate Perepezko and Gonzalez, {Lorenzo L.} and Mills, {Kelly A.} and Pontone, {Gregory M.}",
note = "Funding Information: The authors report no funding pertinent to this manuscript, nor any conflicts of interest, financial or otherwise. PPMI—a public‐private partnership—is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including Abbvie, Allergan, Amathus Therapeutics, Avid Radiopharmaceuticals, Biogen, Biolegend, Bristol‐Myers Squibb, Celgene, Denali, GE Healthcare, Genentech, GlaxoSmithKline, Janssen Neuroscience, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, and Voyager Therapeutics. Golub Capital is a philanthropic funding partner. Funding Sources and Conflicts of Interest: Funding Information: Ethical Compliance Statement: All PPMI centers obtain approval from their respective institutional review boards and written informed consent is obtained from all participants. Research documents, protocols, and specifics are available at www.ppmi-info.org. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflicts of Interest: The authors report no funding pertinent to this manuscript, nor any conflicts of interest, financial or otherwise. PPMI—a public-private partnership—is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including Abbvie, Allergan, Amathus Therapeutics, Avid Radiopharmaceuticals, Biogen, Biolegend, Bristol-Myers Squibb, Celgene, Denali, GE Healthcare, Genentech, GlaxoSmithKline, Janssen Neuroscience, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, and Voyager Therapeutics. Golub Capital is a philanthropic funding partner. Financial Disclosures for the Previous 12 Months: J.T.H.: Receives tuition and stipend support through the Medical Scientist Training Program at the Johns Hopkins School of Medicine (NIH/NIGMS T32GM007309) and through the National Institute on Aging (F30AG067643). K.P.: No disclosures to report. L.L.G.: No disclosures to report. K.M.: Dr. Mills receives salary support through the NIH NCATS (KL2TR001077, PI Daniel Ford) and the NIH/NINDS (5K23NS101096). G.P.: Dr. Pontone receives funding through the NIH/NIA as part of a K23 award (5K23AG044441). Publisher Copyright: {\textcopyright} 2020 International Parkinson and Movement Disorder Society",
year = "2021",
month = jan,
doi = "10.1002/mdc3.13117",
language = "English (US)",
volume = "8",
pages = "76--84",
journal = "Movement Disorders Clinical Practice",
issn = "2330-1619",
publisher = "John Wiley and Sons Ltd",
number = "1",
}