title: COMT polymorphism and memory dedifferentiation in old age.
abstract: According to a neurocomputational theory of cognitive aging, senescent changes in dopaminergic modulation lead to noisier and less differentiated processing. The authors tested a corollary hypothesis of this theory, according to which genetic predispositions of individual differences in prefrontal dopamine (DA) signaling may affect associations between memory functions, particularly in old age. Latent correlations between factors of verbal episodic memory and spatial working memory were compared between individuals carrying different allelic variants of the Catechol-O-Methyltransferase (COMT) Val158Met polymorphism, which influences DA availability in prefrontal cortex. In younger adults (n = 973), correlations between memory functions did not differ significantly among the 3 COMT genotypes (r = .35); in older adults (n = 1333), however, the correlation was significantly higher in Val homozygotes (r = .70), whose prefrontal DA availability is supposedly the lowest of all groups examined, than in heterozygotes and Met homozygotes (both rs = .29). Latent means of the episodic memory and working memory factors did not differ by COMT status within age groups. However, when restricting the analysis to the low-performing tertile of older adults (n = 443), we found that Val homozygotes showed lower levels of performance in both episodic memory and working memory than heterozygotes and Met homozygotes. In line with the neurocomputational theory, the observed dedifferentiation of memory functions in older Val homozygotes suggests that suboptimal dopaminergic modulation may underlie multiple facets of memory declines during aging. Future longitudinal work needs to test this conjecture more directly.
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development.
authors.forename: Goran
authors.initials: G
authors.lastname: Papenberg
authors.affiliation: Aging Research Center, Karolinska Institute.
authors.forename: Lars
authors.initials: L
authors.lastname: Bäckman
authors.affiliation: Department of Education and Psychology, Freie Universität Berlin.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Nagel
authors.affiliation: Max Planck Institute for Molecular Genetics.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Nietfeld
authors.affiliation: Max Planck Institute for Molecular Genetics.
authors.forename: Julia
authors.initials: J
authors.lastname: Schröder
authors.affiliation: Max Planck Institute for Molecular Genetics.
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.affiliation: Department of Education and Psychology, Freie Universität Berlin.
authors.forename: Hauke R
authors.initials: HR
authors.lastname: Heekeren
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development.
authors.forename: Ulman
authors.initials: U
authors.lastname: Lindenberger
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000502:physiology*; D002394:Catechol O-Methyltransferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D061212:Memory, Episodic; D008570:Memory, Short-Term / Q000502:physiology; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D017397:Prefrontal Cortex / Q000378:metabolism; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine; D004298:Dopamine