Atrophy of ventral diencephalon is associated with freezing of gait in Parkinson’s disease: analysis of two cohorts

Evidence regarding brain structural atrophy associated with Freezing of Gait (FOG) in Parkinson's disease (PD) is inconsistent. We analyzed cortical thickness and subcortical nuclei volumes using FreeSurfer in two large PD cohorts. In cohort 1 (N = 316), multivariate analyses identified reduced pallidum and ventral diencephalon (VDC) volumes as significantly associated with FOG presence. Validation in the Parkinson's Progression Markers Initiative (PPMI) cohort (cohort 2, N = 94) demonstrated that decreased VDC volume at four-year follow-up independently predicted higher FOG risk, improving the predictive model's accuracy when combined with PIGD score, CSF Aβ42, and caudate DAT uptake (AUC 0.760; Δχ² = 5.449, P = 0.020; Z = 2.211, P = 0.027). VDC volume is also correlated with FOG severity. These findings suggest that VDC atrophy may underlie FOG mechanisms and serve as a biomarker for its progression in PD patients.