Abstract
Cognitive decline is a major non-motor symptom in Parkinson's disease (PD), often linked to brain atrophy. This study examines the relationship between cortical atrophy and age groups in predicting cognitive decline in PD over five years. 188 PD patients from the COPPADIS cohort were stratified by age: young (30-55 years, N = 47), middle-aged (56-65 years, N = 59), and older adults (66-75 years, N = 82). Baseline cortical volume was assessed using T1-weighted MRI, and cognitive decline was evaluated using the annual rate of change of the Parkinson's Disease-Cognitive Rating Scale (PD-CRS). Parametric or non-parametric tests were applied to evaluate group differences. Main analyses consist of several multiple regression analyses to examine associations between baseline brain atrophy and cognitive decline by age group. Older adults exhibited significantly greater cognitive decline in comparison to the younger age groups in the three compose scores of the PDCRS -Fronto-subcortical (H(2) = 41.08, p < 0.001), Posterior Cortical (H(2) = 22.03, p < 0.001), and Total(H(2) = 41.13, p < 0.001). Higher educational level has a significant positive effect on older adults, specifically for working memory performance, delayed verbal memory and the fronto-subcortical composed score. Multiple regression models underscored the predictive value of the bilateral hippocampus, bilateral medial orbitofrontal cortex, right precuneus, and right isthmus cingulate gyrus, together with being an older adult or having a higher education. MRI measures, age, and education predict cognitive decline in PD. Longitudinal assessments are essential for refining atrophy-cognition correlations and optimizing patient stratification.