ALPS index and choroid plexus volume as indirect MRI biomarkers of glymphatic function for predicting cognitive decline in Parkinson’s disease

• MRI-derived ALPS index and normalized choroid plexus volume (NCPV) were evaluated as biomarkers of glymphatic function in Parkinson’s disease (PD). • PD patients exhibited significantly lower ALPS and higher NCPV compared with healthy controls. • NCPV was independently associated with global cognition and predicted cognitive decline. • Lower ALPS and higher NCPV at baseline predicted steeper longitudinal decline in cognition and memory in the PPMI cohort. • Higher baseline NCPV was linked to increased risk of cognitive conversion in PD. • ALPS index and NCPV may serve as exploratory MRI markers to identify PD patients at risk for cognitive deterioration. Emerging evidence suggests that dysfunction of the brain’s glymphatic system may be relevant to cognitive decline in Parkinson’s disease (PD). However, in vivo indirect imaging correlates and predictive value for disease progression remain unclear. We evaluated whether two MRI-derived indices, diffusion tensor image analysis along the perivascular space (ALPS) and normalized choroid plexus volume (NCPV), are associated with cognitive status and subsequent cognitive decline in PD. This study analyzed a self-collected cohort and the PPMI cohort. ALPS and NCPV were extracted from diffusion tensor imaging and T1-weighted images, respectively. Cross-sectional group comparisons were performed using analysis of covariance. Associations with clinical and cognitive measures were assessed using Spearman correlation and multivariate linear regression. To address stage heterogeneity, we added an early-duration subgroup analysis (PD < 1 year vs healthy controls) in the self-collected cohort. Longitudinal cognitive trajectories were evaluated using linear mixed-effects models, and cognitive conversion was assessed using Kaplan-Meier survival analysis and Cox proportional hazards regression. In the self-collected cohort, PD patients showed significantly lower ALPS and higher NCPV than healthy controls. NCPV was significantly associated with MMSE and showed independent predictive value in regression analysis. In the PD <1 year subgroup, no significant PD-HCs differences were detected for ALPS or NCPV, similar to the early, drug-naïve PPMI cohort where cross-sectional differences were not observed. In the PPMI cohort, lower ALPS and higher NCPV at baseline predicted steeper decline in global cognition and verbal memory over time. Higher baseline NCPV was also associated with increased risk of cognitive conversion . MRI-derived ALPS index and NCPV, while indirect and potentially influenced by multiple factors, were associated with cognitive status and progression in PD. These exploratory markers may aid in identifying individuals at higher risk for cognitive deterioration.