Objective: To identify a large population-based probable REM sleep behavior disorder (pRBD) cohort of women who are at risk of phenoconversion to Parkinson’s disease (PD) or other synucleinopathies.

Background: pRBD is the strongest clinical predictor of synucleinopathy and can precede phenoconversion by many years, with lifetime conversion rates of 80-90%. However, existing cohorts are recruited from tertiary clinics, yielding highly selected populations that may have more severe disease and with marked demographic skew (e.g., male-to-female ratios up to 9:1), limiting generalizability.

Method: In 2012, Nurses’ Health Study (NHS) participants completed a questionnaire including items on pRBD and constipation. Women who were under 85 years of age who reported pRBD or constipation, plus randomly selected controls, were invited in 2015 to a prodromal PD sub-study assessing prodromal features. Among 14,650 women in the prodromal sub-study (excluding 170 with prevalent PD or other synucleinopathies), we defined three baseline strata: pRBD alone; pRBD+1 (hyposmia or constipation); and pRBD+2 (hyposmia and constipation). We calculated the probability of prodromal PD using the Movement Disorders Society (MDS) research criteria.

Results: Of 54,186 respondents to the 2012 questionnaire who were under 85 years, 2741 met pRBD criteria; of whom 1923 completed the 2015 sub-study and had not yet received a synucleinopathy diagnosis. At baseline, 1024 were pRBD only, 762 pRBD+1, and 137 pRBD+2. We identified 133 incident PD and synucleinopathy cases through 2023. Phenoconversion rates were 2% (16/1024), 3% (19/762), and 6% (8/137) across strata. In 2015, 24% (32/133) of women who later developed PD or other synucleinopathies had an MDS-based probability of prodromal PD ≥ 0.5, and 6% (8/133) ≥ 0.8, compared to 5% (646/14,347) and 1% (196/14,347) among women who did not.

Conclusion: We identified a large population-based cohort of women with pRBD whose phenoconversion rates are lower than those reported in clinic-based RBD cohorts. NHS and the prodromal sub-study enable the creation of a scalable, population-based pRBD cohort with systematic assessment of key prodromal PD features. The graded increase in conversion rates across symptom-burden strata supports the utility of combining pRBD with other prodromal markers to identify individuals at highest risk for phenoconversion.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/defining-a-population-based-cohort-of-individuals-with-probable-rem-sleep-behavior-disorder/