Catechol O-methyltransferase Val158Met polymorphism is associated with cognitive performance in nondemented adults

The catechol O-methyltransferase ( COMT) gene is essential in the metabolic degradation of dopamine in the prefrontal cortex. In the present study, we examined the effect of a Val 158 Met polymorphism in the COMT gene on individual differences and changes in cognition ( executive functions and visuospatial ability) in adulthood and old age. The participants were 292 nondemented men ( initially aged 35-85 years) from a random sample of the population (i.e., the Betula study) tested at two occasions with a 5-year interval. Confirmatory factor analyses were used to test the underlying structure of three indicators of executive functions ( verbal fluency, working memory, and Tower of Hanoi). Associations between COMT, age, executive functioning, and visuospatial ( block design) tasks were examined using repeated-measures analyses of variance. Carriers of the Val allele ( with higher enzyme activity) compared with carriers of the Met/Met genotype ( with low enzyme activity) performed worse on executive functioning and visuospatial tasks. Individuals with the Val/Val genotype declined in executive functioning over the 5-year period, whereas carriers of the Met allele remained stable in performance. An Age x COMT interaction for visuospatial ability located the effect for middle-aged men only. This COMT polymorphism is a plausible candidate gene for executive functioning and fluid intelligence in nondemented middle-aged and older adults.