Objective: Examine baseline clinical and biological characteristics of participants with polysomnography-confirmed REM Sleep Behavior Disorder (RBD).

Background: RBD is an early manifestation of underlying synucleinopathy with progression to a clinical synucleinopathy in over 70%. Prevalence of synuclein aggregation in cerebrospinal fluid (CSF) and dopaminergic deficit on DaT scans (D+) in individuals with RBD is not well established. We compare baseline biological and clinical characteristics in RBD between groups distinguished by presence (S+) or absence (S-) of synuclein aggregates.

Method: 297 RBD participants were enrolled in a multicenter prospective longitudinal cohort study, the Parkinson Progression Markers Initiative. Aggregated alpha-synuclein was assessed in CSF using seed amplification assay (SAA) and dopaminergic dysfunction was assessed using SPECT scan. Baseline data were summarized and S+ and S- groups were compared. Participants with MSA-like SAA (3), and clinical diagnosis of Dementia with Lewy Bodies at baseline (n=1) were excluded from the comparison.

Results: At baseline, mean overall age was 67.6 (6.3) years and 79% were male. 70% were SAA+ and 44% were D+ (<75% of age/sex-expected lowest putamen SBR). S+ participants were more frequently hyposmic (UPSIT<15%, 76% vs 12%), orthostatic (27% vs 10%) and had comparatively more dopaminergic deficit (Age/Sex% Expected DAT, 77.9 vs 88.9). Self-reported depression and anxiety were more prominent in the S- group (Geriatric Depression Scale, State-Trait Anxiety Inventory). Motor symptoms (MDS-UPDRS III) and cognitive assessments (MoCA) were not significantly different between groups.

Conclusion: We present biological and clinical data of a large RBD cohort. Nearly three-quarters were S+ and approximately half were D+. This is consistent with the hypothesis that alpha-synuclein aggregation precedes dopaminergic deficit detectable on DaT scan.

The S+ cohort’s biological profile identified hyposmia and presence of dopaminergic deficit, while the S- cohort’s profile identified more self-reported mood disturbances. Longitudinal biological and clinical monitoring in people with RBD will define predictors and timelines of progression and provide opportunities for future interventions.

This abstract will also be presented at the American Academy of Neurology 2025 (this is an updated version).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/biological-characteristics-of-individuals-with-rbd-a-multicenter-prospective-longitudinal-cohort/