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Human aging magnifies genetic effects on executive functioning and working memory

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Item Type:Article
Title:Human aging magnifies genetic effects on executive functioning and working memory
Creators Name:Nagel, I.E. and Chicherio, C. and Li, S.C. and von Oertzen, T. and Sander, T. and Villringer, A. and Heekeren, H.R. and Baeckman, L. and Lindenberger, U.
Abstract:We demonstrate that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. We assess two common Val/Met polymorphisms, one affecting the Catechol-O-Methyltransferase (COMT) enzyme, which degrades dopamine (DA) in prefrontal cortex (PFC), and the other influencing the brain-derived neurotrophic factor (BDNF) protein. In two tasks (Wisconsin Card Sorting and spatial working memory), we find that effects of COMT genotype on cognitive performance are magnified in old age and modulated by BDNF genotype. Older COMT Val homozygotes showed particularly low levels of performance if they were also BDNF Met carriers. The age-associated magnification of COMT gene effects provides novel information on the inverted U-shaped relation linking dopaminergic neuromodulation in PFC to cognitive performance. The modulation of COMT effects by BDNF extends recent evidence of close interactions between frontal and medial-temporal circuitries in executive functioning and working memory.
Keywords:Genes, Dopamine, Executive Functions, Prefrontal Cortex, Aging
Source:Frontiers in Human Neuroscience
ISSN:1662-5161
Publisher:Frontiers Research Foundation (Switzerland)
Volume:2
Page Range:1
Date:3 May 2008
Official Publication:https://doi.org/10.3389/neuro.09.001.2008
PubMed:View item in PubMed

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