Effects of age, genes, and pulse pressure on executive functions in healthy adults.

Executive functions (EF) evidence significant age-related declines, but the mechanisms underpinning those changes are unclear. In this study, we focus on two potential sources of variation: a physiological indicator of vascular health, and genetic variants related to vascular functions. In a sample of healthy adults (n=158, ages 18-81), we examine the effects of age, pulse pressure, and two polymorphisms (comt val158met and ace insertion/deletion) on working memory and cognitive flexibility. Results indicate that in addition to often-replicated age differences, the alleles of two polymorphisms that promote vasoconstriction (comt val and ace D) and reduced availability of dopamine in neocortical synapses (comt val), negatively impact virtually all aspects of EF tasks that involve working memory. In some cases, suppression of cognitive performance is limited to men or necessitates a combination of both risk-associated alleles. After accounting for genetic and age-related variation, pulse pressure had no additional effect on EF. These findings suggest that in healthy adults, the effects of genetic risk factors significantly modulate the course of cognitive aging.