Background: Cognitive deficits such as poor memory, the inability to concentrate, deficits in abstract reasoning, attention and set-shifting flexibility have been reported in middle-aged women. It has been suggested that cognitive decline may be due to several factors which include hormonal changes, individual differences, normal processes of aging and age-related changes in dopaminergic neurotransmission. Catechol-O-methyltransferase (COMT), a common functional polymorphism, has been related to executive performance in young healthy volunteers, old subjects and schizophrenia patients. The effect of this polymorphism on cognitive function in middle-aged healthy women is not well known. The aim of the current study was to investigate whether measures of executive function, sustained attention, selective attention and verbal fluency would be different depending on the COMT genotype and task demand.
Method: We genotyped 74 middle-aged healthy women (48 to 65 years old) for the COMT Val158Met polymorphism. We analyzed the effects of this polymorphism on executive functions (Wisconsin Card Sorting Test), selective attention (Stroop test), sustained attention (Continuous Performance Test) and word generation (Verbal Fluency test), which are cognitive functions that involve the frontal lobe.
Results: There were 27 women with the Val/Val COMT genotype, 15 with the Met/Met genotype, and 32 with the Val/Met genotype. Women carriers of the Val/Val genotype performed better in executive functions, as indicated by a lower number of errors committed in comparison with the Met/Met or Val/Met groups. The correct responses on selective attention were higher in the Val/Val group, and the number of errors committed was higher in the Met/Met group during the incongruence trial in comparison with the Val/Val group. Performance on sustained attention and the number of words generated did not show significant differences between the three genotypes.
Conclusion: These findings indicate that middle-aged women carriers of the Val158 allele, associated with high-activity COMT, showed significant advantage over Met allele in executive processes and cognitive flexibility. These results may help to explain, at least in part, individual differences in cognitive decline in middle-aged women with dopamine-related genes.