Cortical thinning predicts cognitive impairment and progression in Parkinson's disease: The mediating role of p-Tau.

BACKGROUND AND

OBJECTIVE

Clinically accessible biomarkers are critically needed for the early identification of cognitive impairment in Parkinson's disease (PD). This study aimed to investigate the associations of cortical thickness (CTh) and p-Tau with cognitive decline in PD.

METHODS

In this prospective cohort study, 195 PD patients underwent 3 T MRI at baseline. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) at baseline and annually over a 3-year follow-up. CTh was automatically quantified with FreeSurfer. Longitudinal changes were analyzed with linear mixed-effects models, and the risk of cognitive impairment was evaluated with Cox regression.

RESULTS

Baseline global CTh was positively correlated with MoCA scores (r = 0.228, p = 0.001), and this correlation strengthened significantly over the 3-year follow-up (r = 0.405 at Year 3). In Cox models, reduced global CTh predicted future cognitive impairment (HR = 0.156, p = 0.008). Linear mixed-effects models further showed that thinner global CTh was associated with a more rapid decline in MoCA scores over time (CTh × time interaction: estimate = 1.325, p = 0.032). Regional analyses identified specific areas where CTh provided substantially stronger predictive value than the global measure, with the cuneus cortex being the most robust predictor (HR = 0.126, p = 0.001). In contrast, p-Tau was a significant but comparatively weaker predictor (HR = 1.034, p = 0.023). Mediation analysis revealed that baseline CTh explains the cross-sectional association between p-Tau and cognitive performance at 1-year follow-up. A novel observation was that CTh also accounted for the association between GBA-PD status and motor progression.

CONCLUSIONS

CTh represents a robust neuroimaging biomarker for both baseline cognitive performance and longitudinal cognitive decline in PD, demonstrating superior predictive value compared to p-Tau.