Abstract
Dopamine (DA) signaling is critical for optimal cognitive aging, especially in prefrontal-parietal and fronto-striatal networks. Single nucleotide polymorphisms associated with dopamine regulation, COMTVal158Met and DRD2C957T, stand to exert influence on executive function performance via neural properties. The current study investigated whether longitudinal thinning of mesocortical regions is related to COMT and DRD2 genetic predisposition and associated with decline in executive function over four-years. N=235 healthy adults aged 20-94 years were recruited, with n=124 returning 4-years later. Latent mixed effects modeling revealed dopamine-related thinning in several frontal, parietal, and cingulate regions as well as decline in verbal fluency category switching across 4-years. Mesocortical thinning was also related to switching performance. Greater cortical thinning interacted with DA-genotype risk for lower DA-availability to predict poorer switching performance in parietal and posterior cingulate cortex. These findings lend support to the notion that early-life factors, such as genetic influence on neurotransmitter function, play a role in cognitive and brain aging and their linked association.