Beyond motor symptoms: associations between sleep disorders and multidomain functional decline in Parkinson’s disease

Sleep disorders are associated with functional outcomes in Parkinson’s disease (PD), yet their multidomain clinical correlates remain incompletely characterized. We analyzed 9195 participants from the National Alzheimer’s Coordinating Center database using inverse probability weighting (IPW) to balance measured covariates between PD patients and controls. Associations of REM sleep behavior disorder (RBD), insomnia, and sleep apnea with motor, cognitive, neuropsychiatric, and instrumental activities of daily living (IADL) outcomes were evaluated using logistic regression, exploratory sequential mediation, and machine learning. RBD showed the broadest multidomain association profile, including stronger associations with bradykinesia, hallucinations, and selected IADL impairments. Insomnia showed a more mixed profile, with neuropsychiatric associations but inverse or null associations for several IADL items, whereas sleep apnea showed more circumscribed associations. RF models showed the strongest discrimination for RBD (AUC = 0.851) and lower discrimination for insomnia and sleep apnea (AUC = 0.667 and 0.666, respectively). Exploratory SEM results were compatible with a motor-related indirect pathway between sleep disorders and IADL impairment (Sleep -> Motor -> IADL; statistical mediation proportion, 35.8%), whereas cognitive and neuropsychiatric pathways showed suppression patterns. Overall, distinct sleep disorders in PD were associated with different functional profiles. These findings support cautious, disorder-specific screening hypotheses that require longitudinal and interventional validation before clinical implementation.