Objective: To determine if secular changes occur in REM sleep behavior disorder (RBD).

Background: RBD is the strongest clinical marker of prodromal synucleinopathy, and provides an unprecedented opportunity to potentially intervene with neuroprotective therapy. In two recent international multicenter studies, we identified clinical predictors of phenoconversion, determined optimal clinical trial outcomes, and estimated the overall rate of phenoconversion to overt disease.^1,2 A lingering question remains whether clinical progression and phenoconversion rates remain stable over time or if they are subject to secular change: as a disease becomes increasingly recognized, milder/earlier cases (with lower phenoconversion and progression rates) may come to attention earlier.

Method: Clinical profiles and rates of clinical progression were compared in two recruitment epochs in one center (Montreal): those recruited between 2004-2013 (‘early epoch’) vs. those recruited between 2014-2022 (‘late epoch’). We compared our findings with two other centers that recruited over the same time period (Barcelona and Innsbruck). We next determined if secular changes were resultant from increased patient awareness of iRBD as determined by those referring themselves directly to the clinic (‘self-referral’) vs. those referred by their physicians (‘conventional referral’).

Results: In Montreal, 209 subjects (early epoch=101; late epoch=108) were followed over a mean of 4.5±3.4 years. Significantly decreased survival time to phenoconversion was observed in the early epoch (5-year survival early epoch=58%; late epoch=77%, p=0.015). Multivariate Cox proportional hazards modeling showed reduced risk of phenoconversion with each successive year of enrolment (HR 0.92 [0.88, 0.97], p=0.003). Improved survival in the late epoch was driven by increased number of self-referrals, which showed a 70% decreased risk of phenoconversion relative to conventional referral (HR 0.30 [0.10, 0.92], p=0.036). No difference in survival was observed between epochs in Barcelona or Innsbruck, which did not include self-referrals.

Conclusion: Increased patient awareness of iRBD results in earlier presentation to clinical attention and secular changes in disease progression. As we begin to design and recruit patients for neuroprotective trials, this has important implications on optimal clinical endpoints.

References: 1. Postuma RB, Iranzo A, Hu M, et al. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study [Internet]. Brain 2019;142(3):744–759.[cited 2021 Oct 20 ] Available from: https://academic-oup-com.login.ezproxy.library.ualberta.ca/brain/article/142/3/744/5353011

2. Joza S, Hu MT, Jung K-Y, et al. Progression of clinical markers in prodromal Parkinson’s disease and dementia with Lewy bodies: a multicentre study [Internet]. Brain 2023;139(4):16–17.[cited 2023 Mar 12 ] Available from: https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awad072/7071614

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MDS Abstracts - https://www.mdsabstracts.org/abstract/are-patients-presenting-earlier-in-time-secular-changes-in-rem-sleep-behavior-disorder/