Objective: To compare the proportion of people with abnormal alpha-synuclein among groups with differing levels of certainty of REM sleep behavior disorder (RBD).

Background: REM sleep behavior disorder (RBD) is a parasomnia defined by dream enactment behavior (DEB) and absence of atonia during REM sleep on polysomnogram (PSG). PSG-confirmed RBD is a highly specific feature of early alpha-synucleinopathy, but PSG is not practical for large-scale screening. DEB is commonly reported, but only a subset have RBD. Accurate yet scalable methods to identify the subset of people with DEB with alpha-synuclein (aSyn) pathology are needed.

Method: We used data from the Parkinson’s Progression Markers Initiative (PPMI). Among participants without a diagnosis of Parkinson’s disease (PD), participants were eligible for enrollment and testing for cerebrospinal fluid aSyn seed amplification assay (aSyn SAA) through two pathways: (1) RBD confirmed on PSG (RBD-PSG) or (2) self-report of RBD or DEB and hyposmia (defined by a University of Pennsylvania Smell Identification Test (UPSIT) score <10^th percentile) and reduced dopaminergic transporter (DAT) binding (defined as minimum putaminal specific binding ratio (mSBR) of <100% of expected for age and sex). RBD-PSG participants were identified through clinical sites while participants with RBD/DEB with hyposmia were identified either through sites or remote screening. To determine whether participants differed in clinical severity, we compared clinical assessments completed at the PPMI baseline visit across groups.

Results: As of January 2024, 269 participants with either RBD-PSG (n = 156), self-reported RBD with hyposmia (n = 65; RBD-Hypos), or no diagnosis of RBD but DEB with hyposmia (n = 48, DEB-Hypos) were enrolled [Table 1]. Relatively more RBD-Hypos and DEB-Hypos had positive aSyn SAA compared to RBD-PSG. When RBD-PSG were limited to UPSIT < 10^th %ile and mSBR < 100 % (n = 77/156), a similar proportion had aSyn SAA (74/77 [96%]).  Clinical assessments between groups were similar, except the RBD Screening Questionnaire was higher in RBD-PSG [Table 2].

Conclusion: Smell testing may be a scalable way to identify people with synucleinopathy among those self-reporting dream enactment behavior.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/comparison-of-olfactory-testing-and-psg-for-detection-of-alpha-synuclein-pathology-in-patients-with-dream-enactment-behavior-or-rem-sleep-behavior-disorder/