Obstructive sleep apnea, biomarker profiles, and clinical progression in Parkinson's disease: Longitudinal effects of CPAP therapy.

BACKGROUND: Obstructive sleep apnea (OSA) is common in Parkinson's disease (PD) and may exacerbate neurodegeneration via inflammatory and glial mechanisms, yet longitudinal biomarker data are scarce. We aimed to compare inflammatory, glial, and neurodegenerative biomarkers in PD patients with and without OSA, assess associations between OSA severity and biomarker levels, evaluate biomarker-symptom relationships, and determine the longitudinal effects of continuous positive airway pressure (CPAP) therapy on clinical and biomarker outcomes. METHODS: In this 12-month prospective cohort study, 140 PD patients (PD + OSA n = 72; PD-OSA n = 68) underwent polysomnography, clinical evaluations, and blood/CSF sampling. Biomarkers included IL-1β, IL-18, IL-6, TNF-α, CRP, CHI3L1, S100B, GFAP, and NfL. Cross-sectional and longitudinal associations were analyzed using multivariable regression and linear mixed-effects models. CPAP-treated participants were stratified by adherence. Mediation analyses (5000 bootstraps) assessed pathways linking biomarker changes to clinical improvement. RESULTS: Among 140 patients with Parkinson's disease (PD), 72 (51.4 %) had obstructive sleep apnea (OSA). PD + OSA showed higher BMI (27.41 vs 25.92 kg/m CONCLUSIONS: OSA substantially enhances inflammatory, glial, and neuroaxonal injury pathways in PD and contributes to worse motor, non-motor, and cognitive outcomes. CPAP therapy attenuates these pathological processes and improves clinical symptoms, suggesting a mechanistic basis for incorporating OSA screening and treatment into comprehensive PD management.