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- Papenberg, Göran, et al.
(author)
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COMT polymorphism and memory dedifferentiation in old age
- 2014
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In: Psychology and Aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 29:2, s. 374-383
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Journal article (peer-reviewed)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.
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2. |
- Papenberg, Goran, et al.
(author)
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Dopamine and glutamate receptor genes interactively influence episodic memory in old age
- 2014
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 35:5
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Journal article (peer-reviewed)abstract
- Both the dopaminergic and glutamatergic systems modulate episodic memory consolidation. Evidence from animal studies suggests that these two neurotransmitters may interact in influencing memory performance. Given that individual differences in episodic memory are heritable, we investigated whether variations of the dopamine D2 receptor gene (rs6277, C957T) and the N-methyl-D-aspartate 3A (NR3A) gene, coding for the N-methyl-D-aspartate 3A subunit of the glutamate N-methyl-D-aspartate receptor (rs10989591, Val362Met), interactively modulate episodic memory in large samples of younger (20-31 years; n = 670) and older (59-71 years; n = 832) adults. We found a reliable gene-gene interaction, which was observed in older adults only: older individuals carrying genotypes associated with greater D2 and N-methyl-D-aspartate receptor efficacy showed better episodic performance. These results are in line with findings showing magnification of genetic effects on memory in old age, presumably as a consequence of reduced brain resources. Our findings underscore the need for investigating interactive effects of multiple genes to understand individual difference in episodic memory.
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