Risk Factors for Phenoconversion in Rapid Eye Movement Sleep Behavior Disorder

Ann Neurol. 2022 Mar;91(3):404-416. doi: 10.1002/ana.26298. Epub 2022 Jan 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Dementia / epidemiology*
  • Dementia / etiology
  • Disease Progression
  • Follow-Up Studies
  • Humans
  • Incidence
  • Life Style
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / epidemiology*
  • Neurodegenerative Diseases / etiology
  • REM Sleep Behavior Disorder / complications*
  • Risk Factors
  • Surveys and Questionnaires

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