Frontoparietal cortical thickness mediates the effect of COMT Val158Met polymorphism on age-associated executive function.

摘要: Abstract Proper dopamine (DA) signaling is likely necessary for maintaining optimal cognitive performance as we age, particularly in prefrontal-parietal networks and fronto-striatal networks. Thus, reduced DA availability a salient risk factor accelerated aging. A common polymorphism that affects D1 receptor availability, COMT Val158Met (rs4680), influences enzymatic breakdown of DA, with Val carriers having 3- to 4-fold reduction synaptic compared Met carriers. Furthermore, receptors postsynaptic are drastically aging, executive function ostensibly relies on these pathways. Here, investigated 176 individuals aged 20–94 years whether: (1) differ from their counterparts thickness regional cortices receiving pathways: prefrontal, parietal, cingulate cortices; (2) this gene-brain association differs across the adult lifespan; (3) COMT-related thinning evidences consequences. We found evidenced thinner cortex posterior than effect was not age-dependent. Further, demonstrate regions significantly mediates genotype an composite measure. These results suggest poorer due partly dopaminergic-rich regions, so who genetically predisposed lower regardless age.