Reduced gray matter volume in cognitively preserved COMT 158 Val/Val Parkinson's disease patients and its association with cognitive decline.

The COMT Val158 Met polymorphism has recently been identified as a predictor for cognitive decline in Parkinson's disease (PD). However, it remains unknown whether an early brain structural compromise could be involved in this clinical association. Here, in a cohort of 120 cognitively preserved de novo PD patients from the Parkinson's Progression Markers Initiative (PPMI) database, we found a widespread reduction in cerebral gray matter volume (GMV) in patients harboring the Val/Val genotype. The atrophic pattern included fronto-subcortical and parieto-temporal territories. Importantly, the GMV at some of the identified regions was associated with cognitive decline in a 4-year follow-up period. These findings suggest that GMV compromise in the early stages of PD may be a predisposing factor for cognitive decline of COMT Val/Val homozygotes.