Subcortical Brain-Age Gaps Reveal Asymmetric Aging Patterns in Parkinson's Disease With Cognitive Impairment

The study utilized MRI-derived brain structure age (BSA) to compare global and regional subcortical BSA among healthy controls (HCs), Parkinson's disease (PD) patients with normal cognition (PD-NC), and mild cognitive impairment (PD-MCI), identifying regions with accelerated aging and linking altered BSA to native volumes.

We analyzed structural MRI data from 55 participants (22 HCs, 18 PD-NC, 15 PD-MCI) using the volBrain platform to estimate global and regional subcortical BSA. Group differences in age, global, and regional BSA were tested via Kruskal-Wallis. Follow-up analyses included Pearson correlations for significant regions and ANOVAs where assumptions were met.

No significant group differences were found for chronological age (p = 0.111) or global BSA (p = 0.143). However, at the regional level, non-parametric analyses revealed significant group differences in the predicted age of the left amygdala (H = 6.42, p = 0.040) and the left basal forebrain (H = 6.01, p < 0.05), though effect sizes were small (ε² ≤ 0.07). The predicted ages of these two regions were highly collinear (r = 0.992). Subsequent parametric tests and Bonferroni-corrected pairwise comparisons on other subcortical regions did not yield any significant differences.

Accelerated aging appears to be a localized and asymmetric process confined to the limbic-cholinergic network, specifically involving the left amygdala and basal forebrain. Accelerated brain aging in PD is not global but a localized, asymmetric process in the left limbic-cholinergic network. Regional brain-age metrics offer a sensitive biomarker for detecting the specific neurodegeneration linked to cognitive decline.