Metabolic and dopaminergic correlates of intellectual enrichment in de-novo Parkinson's disease patients.

Abstract

Background: Cognitive reserve (CR) is an expression of brain resilience in response to damage. Education, occupational experience and leisure activities are thought to increase CR and have beneficial effects on global cognition and cognitive decline in Parkinson's disease (PD). We aimed to disclose brain metabolic and dopaminergic correlates of CR in de-novo PD patients.

Methods: Sixty-two drug-naïve de-novo PD patients underwent [¹⁸F]FDG-PET and DAT-SPECT. CR was quantified through the Cognitive-Reserve-Index questionnaire including total-CR and 3 subscores (educational-CR, occupational-CR, leisure-CR). Specific binding ratios (SBRs) and Z-scores in basal ganglia were obtained with 'BasGan-V2'. Z-scores were used as dependent variables in general linear models to assess the interaction between dopaminergic function and CR. Voxel-based correlation between brain metabolism and CR-scores and between SBR and [¹⁸F]FDG-PET was evaluated using SPM12 (P<0.05 FWE-corrected at peak and cluster level considered significant).

Results: Dopaminergic deficit in the most affected hemisphere (MAH) putamen was significantly less marked in higher CR patients (Z-score -1.7±0.1 highly-educated versus -2.1±0.1 poorly-educated, P<0.02). Total and leisure-related-CR resulted correlated directly with z-scores of the MAH putamen (P<0.018 and P<0.003) and inversely with brain metabolism in both cerebellar hemispheres (P<0.001). MAH-putamen SBR correlated directly with metabolism in occipital and parietal cortex (P<0.003) and inversely in cerebellar hemispheres (P<0.02).

Conclusions: CR proxies demonstrated to correlate directly with dopaminergic function and inversely with metabolism in cerebellar hemispheres in de-novo PD patients. The present multi-modal approach including both metabolic and dopaminergic correlates of CR allowed to identify possible compensation mechanisms, highlighting a potential role of the cerebellum that deserves further investigation.