OBJECTIVE: This study was undertaken to follow up predictive factors for α-synuclein-related neurodegenerative diseases in a multicenter cohort of idiopathic/isolated rapid eye movement sleep behavior disorder (iRBD). METHODS: Patients with iRBD from 12 centers underwent a detailed assessment for potential environmental and lifestyle risk factors via a standardized questionnaire at baseline. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow-up. The cumulative incidence of parkinsonism or dementia was estimated with competing risk analysis. Cox regression analyses were used to evaluate the predictive value of environmental/lifestyle factors over a follow-up period of 11 years, adjusting for age, sex, and center. RESULTS: Of 319 patients who were free of parkinsonism or dementia, 281 provided follow-up information. After a mean follow-up of 5.8 years, 130 (46.3%) patients developed neurodegenerative disease. The overall phenoconversion rate was 24.2% after 3 years, 44.8% after 6 years, and 67.5% after 10 years. Patients with older age (adjusted hazard ratio [aHR] = 1.05) and nitrate derivative use (aHR = 2.18) were more likely to phenoconvert, whereas prior pesticide exposure (aHR = 0.21-0.64), rural living (aHR = 0.53), lipid-lowering medication use (aHR = 0.59), and respiratory medication use (aHR = 0.36) were associated with lower phenoconversion risk. Risk factors for those converting to primary dementia and parkinsonism were generally similar, with dementia-first converters having lower coffee intake and beta-blocker intake, and higher occurrence of family history of dementia. INTERPRETATION: Our findings elucidate the predictive values of environmental factors and comorbid conditions in identifying RBD patients at higher risk of phenoconversion. ANN NEUROL 2022;91:404-416.

C Mondino National Neurological Institute Pavia Italy

Center for Advanced Studies in Sleep Medicine Montreal Sacred Heart Hospital Montreal Quebec Canada

Department of Neurology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Neurology Dokkyo Medical University Saitama Medical Center Saitama Japan

Department of Neurology Dokkyo Medical University School of Medicine Tochigi Japan

Department of Neurology Gui de Chauliac Hospital Montpellier National Institute of Health and Medical Research U1061 Montpellier France

Department of Neurology Innsbruck Medical University Innsbruck Austria

Department of Neurology McGill University Montreal General Hospital Montreal Quebec Canada

Department of Neurology Philipps University Marburg Germany

Department of Neurology University of Auvergne Clermont Ferrand France

Department of Neurology Washington University School of Medicine St Louis MO USA

Department of Neurology Xuanwu Hospital Capital Medical University Beijing China

Department of Psychiatry University of Montreal Montreal Quebec Canada

Neurology Service Hospital Clinic of Barcelona August Pi i Sunyer Biomedical Research Institute Center for Biomedical Research on Neurodegenerative Diseases Barcelona Spain

Paris Brain Institute and Sleep Disorder Unit Pitié Salpêtrière Hospital Public Hospital Network of Paris Sorbonne University Paris France

Sleep Center Department of Cardiovascular and Neurological Sciences University of Cagliari Cagliari Italy

Sleep Disorders Center Vita Salute San Raffaele University Milan Italy

J Parkinsons Dis. 2022;12(5):1619-1620. doi: 10.3233/JPD-223306. PubMed

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Presynaptic Dopaminergic Imaging Characterizes Patients with REM Sleep Behavior Disorder Due to Synucleinopathy