Characterizing Parkinson's Disease Clinical and Biomarker Interactions in REM Sleep Behavior Disorder.

Background: REM Sleep Behavior Disorder (RBD), marked by dream enactment due to 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 events 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. 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 associated with reductions in striatal DaT binding and α-syn SAA positivity. MDS Prodromal PD Probability Scores, which incorporate DaT and olfactory function, predicted SAA positivity and phenoconversion. DaT positivity was much more common (80%) among phenoconverters (RBD-PC), than non-phenoconverters (10%). 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 stratification factors in clinical research study design.