Choroid Plexus Microstructural Alterations Link Glymphatic Dysfunction and White Matter Degeneration in Parkinson's Disease.

OBJECTIVES: Glymphatic dysfunction is increasingly recognized as a key contributor to the progression of Parkinson's disease (PD). In PD, both choroid plexus (CP) alterations and white matter abnormalities have been linked to glymphatic dysfunction. However, how CP microstructural abnormalities relate to glymphatic function, corpus callosum (CC) degeneration, and clinical impairment remains unclear. This study aimed to investigate these associations in PD. METHODS: Eighty-one patients with idiopathic PD and eighty age- and sex-matched healthy controls (HC) underwent MRI scanning. CP microstructural metrics (free water [FW], FW-corrected fractional anisotropy [FAFWcorr] and FW-corrected mean diffusivity [MDFWcorr]) were extracted, along with the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and CC subregional volumes. Group comparisons, partial correlation, multiple linear regression, and mediation analyses were performed. RESULTS: Patients with PD showed significantly higher CP FW and MDFWcorr values and a lower DTI-ALPS index than HC. Higher CP MDFWcorr was associated with worse motor symptoms and poorer cognitive performance after covariate adjustment. Mediation analysis suggested that the ALPS index mediated the associations between CP microstructural alterations and CC subregional volumes. CONCLUSIONS: CP microstructural abnormalities were associated with DTI-ALPS alterations, CC degeneration, and clinical impairment in PD. FW-DTI metrics of the CP may provide useful imaging markers for characterizing CP-related changes in PD.