Abstract
BackgroundCognitive 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.MethodWe 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.ResultsThere 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.ConclusionThese 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.
Highlights
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 associated with age may be due to several factors which include hormonal changes [4,5], normal processes of aging [6,7], age-related changes in dopaminergic neurotransmission [8] and interindividual variations in brain function and cognitive abilities associated with genetic factors [9,10]
A behavioral genetic approach may help to explain, at least in part, the cognitive decline associated with age in middle-aged women, in the modulation of the cognitive functions mediated by the prefrontal cortex (PFC) [7]
Summary
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. 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. Some studies report harmful associations, some protective and many fail to identify a clinically meaningful association between serum estrogen levels and cognitive ability [5] These discrepancies may be due to methodological problems, such as failure to match groups on basic demographic characteristics, inadequate exclusionary criteria, the tests employed to assess cognition and insufficient control for affective disturbances are probably responsible, at least in part, for some of the contradictory findings [2,5]. One widely used approach is to relate allelic variants for functional measures at a biochemical or behavioral level, which has helped explain some cognitive deficits associated with age [8]
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