Sleep disturbance is associated with CSF N1-synuclein in Parkinson's disease

Background: Sleep disturbance is highly prevalent in Parkinson’s disease (PD) and contributes to impaired quality of life and functional outcomes. Cerebrospinal fluid (CSF) α-synuclein is a widely studied biomarker candidate reflecting synucleinopathy biology, though assay variability and clinical heterogeneity complicate interpretation. Whether subjective sleep disturbance is associated with CSF α-synuclein levels remains of interest given converging links between sleep, neurodegeneration, and protein homeostasis.Objective: To present a complete publication-style workflow evaluating the association between sleep disturbance severity and CSF α-synuclein in PD using a cohort and clinically familiar sleep and PD covariates.Methods: A dataset was used comprising 150 adults meeting PD phenotype criteria, with demographics, disease duration, Hoehn & Yahr stage, levodopa equivalent daily dose (LEDD), cognition (MoCA), depressive symptoms (BDI-II), and sleep measures (Pittsburgh Sleep Quality Index [PSQI], Epworth Sleepiness Scale [ESS], and a REM sleep behavior disorder questionnaire score [RBDQ]). The primary exposure was PSQI (continuous), with a secondary group definition PSQI≥8. The outcome was CSF α-synuclein (pg/mL). Multivariable linear regression assessed the association between PSQI and CSF α-synuclein adjusting for age, sex, disease duration, Hoehn & Yahr stage, LEDD, MoCA, and BDI-II.Results: In this cohort, 13.2% met PSQI≥8. Higher PSQI was associated with lower CSF α-synuclein in adjusted analyses. Group comparisons showed lower CSF α-synuclein in the PSQI≥8 group.Conclusions: The current study demonstrates an end-to-end reproducible workflow for testing associations between sleep disturbance and CSF α-synuclein in PD using standard sleep questionnaires and clinically meaningful covariates. The schema is readily adaptable for real-world cohorts.