Cognitive Reserve proxies can modulate motor and non-motor basal ganglia circuits in early Parkinson's Disease

Parkinson's Disease (PD) is hallmarked by dysfunctional circuitry between the basal ganglia and dorsolateral-prefrontal cortex. Recently progress has been made in understanding factors contributing to differential susceptibility to pathology mitigating disease-related cognitive decline. Cognitive reserve, the brain processing resources accumulated throughout life while engaged in mentally stimulating activities, can play an important protective role in cognitive performance. We tested the hypothesis that Cognitive Reserve proxies may exert an impact on the basal ganglia and dorsolateral-prefrontal atrophy in early PD. Forty-five early patients with PD and 20 age-gender-matched healthy controls (HC) completed the Cognitive Reserve Index questionnaire to quantify Cognitive Reserve proxies by three indexes (CRI-Education, CRI-Working Activity, CRI-Leisure Time) and a structural MRI examination (3T). Morphometrical indexes for basal ganglia (bilateral putamen, caudate, pallidum volume) and dorsolateral-prefrontal cortex (cortical thickness) were computed. Significant differences between HC and PD were tested by direct comparisons in demographics, cognitive level, and cognitive reserve proxies indexes. Then two multiple regression analyses were performed to identify predictors of the basal ganglia and dorsolateral-prefrontal cortex structural integrity. Regression analysis revealed that basal ganglia volume was significantly predicted by CRI-Education (p_FDR = 0.029), sex (p_FDR = 0.029), and Total Intracranial Volume (p_FDR < 0.001). Instead, the dorsolateral-prefrontal thickness was predicted by CRI-Leisure Time (p_FDR = 0.030) and age (p_FDR = 0.010). Cognitive Reserve proxies, especially education and leisure-time activities, can play a protective role on the structural integrity of the basal ganglia and dorsolateral-prefrontal cortex, respectively, critical regions hallmarking brain status of early phases of PD.