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

Journal article
Authors Cindy M de Frias
Kristina Annerbrink
Lars Westberg
Elias Eriksson
Rolf Adolfsson
Lars-Göran Nilsson
Published in Journal of cognitive neuroscience
Volume 17
Issue 7
Pages 1018-25
ISSN 0898-929X
Publication year 2005
Published at Institute of Physiology and Pharmacology, Dept of Pharmacology
Pages 1018-25
Language en
Keywords Adult, Age Factors, Aged, Aged, 80 and over, Analysis of Variance, Catechol O-Methyltransferase, genetics, physiology, Cognition, physiology, Factor Analysis, Statistical, Humans, Male, Memory, Short-Term, physiology, Methionine, genetics, Middle Aged, Molecular Biology, methods, Neuropsychological Tests, statistics & numerical data, Polymorphism, Genetic, Problem Solving, physiology, Retrospective Studies, Valine, genetics, Verbal Behavior, physiology
Subject categories Physiology


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 Val158Met 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.

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