COMT Gene Polymorphism Is Associated with Declarative Memory in Adulthood and Old Age

Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35–85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.

[1]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[2]  Ronald T. Borchardt,et al.  [34] Catechol O-methyltransferase , 1981 .

[3]  I. Ulmanen,et al.  Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. , 1995, Biochemistry.

[4]  Endel Tulving,et al.  Organization of memory: Quo vadis? , 1995 .

[5]  Lars Nyberg,et al.  Classifying Human Long-term Memory: Evidence from Converging Dissociations , 1996 .

[6]  R. Weinshilboum,et al.  Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. , 1996, Pharmacogenetics.

[7]  R. Plomin.  Current Directions in Behavioral Genetics , 1997 .

[8]  R. Dolan,et al.  The Neural Correlates of the Noradrenergic Modulation of Human Attention, Arousal and Learning , 1997, The European journal of neuroscience.

[9]  L. Nyberg,et al.  The betula prospective cohort study: Memory, health, and aging , 1997 .

[10]  W. Koller,et al.  Mechanism of action of dopaminergic agents in Parkinson's disease , 1998, Neurology.

[11]  A. Alessandri,et al.  Can COMT Inhibitors Improve Cognitive Functions in Patients with Parkinson’s Disease? , 2000 .

[12]  R. Dixon,et al.  Age-related cognitive deficits mediated by changes in the striatal dopamine system. , 2000, The American journal of psychiatry.

[13]  R. Straub,et al.  Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[14]  D. Boomsma,et al.  Editorial: Genetics of Brain Function and Cognition , 2001, Behavior genetics.

[15]  M. Egan,et al.  Prefrontal neurons and the genetics of schizophrenia , 2001, Biological Psychiatry.

[16]  J. Lieberman,et al.  Neurocognitive correlates of the COMT Val158Met polymorphism in chronic schizophrenia , 2002, Biological Psychiatry.

[17]  A. Malhotra,et al.  A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition. , 2002, The American journal of psychiatry.

[18]  L. Nyberg,et al.  Memory development in adulthood and old age: the Betula prospective cohort study , 2002 .

[19]  P. Arner,et al.  Large‐scale genotyping of single nucleotide polymorphisms by Pyrosequencing™ and validation against the 5′nuclease (Taqman®) assay , 2002 .

[20]  C. Benkelfat,et al.  Catechol-O-methyltransferase Val-108/158-Met gene variants associated with performance on the Wisconsin Card Sorting Test. , 2002, Archives of general psychiatry.

[21]  A. Nieoullon.  Dopamine and the regulation of cognition and attention , 2002, Progress in Neurobiology.

[22]  L. Nyberg,et al.  Genetic variation in memory functioning , 2002, Neuroscience & Biobehavioral Reviews.

[23]  R. Dixon,et al.  Selective adult age differences in an age-invariant multifactor model of declarative memory. , 2003, Psychology and aging.

[24]  P. Schlattmann,et al.  Association of the G1947A COMT (Val108/158Met) gene polymorphism with prefrontal P300 during information processing , 2003, Biological Psychiatry.

[25]  Shih-Jen Tsai,et al.  Association study of a functional catechol-O-methyltransferase-gene polymorphism and cognitive function in healthy females , 2003, Neuroscience Letters.

[26]  B. Kolachana,et al.  Catechol-O-Methyltransferase Genotype and Dopamine Regulation in the Human Brain , 2003, The Journal of Neuroscience.

[27]  R. Coppola,et al.  Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. , 2003, Archives of general psychiatry.

[28]  M. Egan,et al.  Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[29]  A. Antal,et al.  Dopaminergic contributions to the visual categorization of natural scenes: evidence from Parkinson's disease , 2003, Journal of Neural Transmission.

[30]  L. Nyberg,et al.  Betula: A Prospective Cohort Study on Memory, Health and Aging , 2004 .