Objective: To determine if baseline biomarkers predict baseline and progression of clinical domains in isolated REM sleep behavior disorder (iRBD).
Background: iRBD has high conversion rate to Lewy body disorders (PD and DLB), but studies have not assessed associations between presence of synucleinopathy, dopaminergic deficiency, amyloid and tau biomarkers, olfaction and other biomarkers on clinical course.
Method: PSG-confirmed iRBD (N=287) and robust healthy controls (HCs; N=141) from Parkinson’s Progression Markers Initiative. Biomarker predictors were: CSF α-synuclein SAA test, DaTscan, plasma p-tau 217, CSF p-tau 181:AB42 and AB42:40, UPSIT, and orthostatic hypotension (OH). Clinical longitudinal outcomes (out to 3 years post-baseline) were changes in cognitive performance (MoCA) and motor symptoms (MDS-UPDRS Part III). Kaplan-Meier graphs were used for survival analyses.
Results: iRBD participants were 79% male, mean (SD) age 67 (6), mean MoCA score 26.5 (2.6), mean MDS-UPDRS Part III score 4.5 (4.8), 79% SAA+, 39% abnormal DaTscan, 65% hyposmia, and 23% with OH. Regarding outcomes, for cognitive decline over time, there was a suggestion for higher baseline p-tau217 predicting MoCA cut-off score ≤25 (p=0.10), while lower baseline AB42:AB40 predicted MoCA decrease ≥2 points (p=0.04) and abnormal baseline DaTscan (lowest putamen SBR <75%ile) predicted MoCA cut-off score ≤25 (p=0.03). For motor worsening, abnormal baseline DaTscan predicted MDS-UPDRS Part III score increase ≥5 points (p=0.10). Presence of synucleinopathy status, hyposmia, and OH did not predict motor or cognitive outcomes.
Conclusion: Baseline amyloid and tau biomarkers may predict future cognitive decline in iRBD, while baseline dopaminergic dysfunction may predict both future cognitive and motor decline. These results suggest that there are multiple neurobiological contributions to cognitive decline in iRBD, and that dopaminergic dysfunction impacts both motor and cognitive abilities. Over the short-term, amyloid, tau and dopaminergic biomarkers may predict cognitive and motor decline more than presence of synucleinopathy, hyposmia, and OH do.
To cite this abstract in AMA style:
D. Weintraub. Biological Predictors of Clinical Domains in Isolated REM Sleep Behavior Disorder with and without Synucleinopathy and Dopamine Dysfunction [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/biological-predictors-of-clinical-domains-in-isolated-rem-sleep-behavior-disorder-with-and-without-synucleinopathy-and-dopamine-dysfunction/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/biological-predictors-of-clinical-domains-in-isolated-rem-sleep-behavior-disorder-with-and-without-synucleinopathy-and-dopamine-dysfunction/