Risk Factors for Phenoconversion in Rapid Eye Movement Sleep Behavior Disorder

Hui Zhang, Alex Iranzo, Birgit Högl, Isabelle Arnulf, Luigi Ferini-Strambi, Raffaele Manni, Tomoyuki Miyamoto, Wolfgang H. Oertel, Yves Dauvilliers, Yo EI Ju, Monica Puligheddu, Karel Sonka, Amélie Pelletier, Jacques Y. Montplaisir, Ambra Stefani, Abubaker Ibrahim, Birgit Frauscher, Smaranda Leu-Semenescu, Marco Zucconi, Michele TerzaghiMasayuki Miyamoto, Annette Janzen, Michela Figorilli, Maria L. Fantini, Ronald B. Postuma

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish
Pages (from-to)404-416
Number of pages13
JournalAnnals of neurology
Issue number3
StatePublished - Mar 2022


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