Characterizing Parkinson’s Disease Clinical and Biomarker Interactions in REM Sleep Behavior Disorder
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Background
REM Sleep Behavior Disorder (RBD), marked by dream enactment due to the loss of REM-related muscle atonia, is a prominent prodromal indicator of synucleinopathies, particularly Parkinson’s Disease (PD).
Objectives
This study aimed to investigate the interplay among key PD biomarkers— α-synuclein seed amplification assay (SAA), hyposmia, and dopamine transporter (DaT) SPECT imaging — in individuals with RBD. Additionally, we evaluated how phenoconversion and Movement Disorder Society (MDS)-Prodromal PD probability scores relate to clinical symptoms and biomarker profiles in an incident RBD population.
Methods
Participants with polysomnographically-confirmed RBD underwent comprehensive clinical and biomarker assessments. Post hoc, they were grouped along three non-exclusive biomarker-based axes (hyposmic vs. normosmic, SAA positive vs. SAA negative, and DaT positive vs. intermediate vs. negative) and two clinical outcome-based axes (high vs. intermediate/low MDS-Prodromal PD probability; phenoconverters vs. non-phenoconverters). Within each category, performance on various clinical assessments, the presence of other biomarkers, and clinical outcomes were evaluated.
Results
Hyposmia was strongly associated with reductions in striatal dopaminergic activity and α-syn SAA positivity. MDS Prodromal PD Probability Scores, which incorporate DaT and olfactory function, predicted SAA positivity and phenoconversion. Among six phenoconverters (RBD-PC), DaT positivity was much more common (80%) than in non-phenoconverters (10%), but no significant motor or non-motor symptom differences were observed between the two groups at baseline, likely due to the small sample size.
Conclusions
α-syn SAA positivity, DaT positivity, and hyposmia are highly associated with each other. MDS Prodromal PD Probability scores may be useful predictors of near-term progression, and thus as a stratification factor in clinical research study design.
