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Human aging magnifies genetic effects on executive functioning and working memory.

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.

SUBMITTER: Nagel IE

PROVIDER: S-EPMC2525971 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Human aging magnifies genetic effects on executive functioning and working memory.

Nagel Irene E IE Chicherio Christian C Li Shu-Chen SC von Oertzen Timo T Sander Thomas T Villringer Arno A Heekeren Hauke R HR Bäckman Lars L Lindenberger Ulman U

Frontiers in human neuroscience 20080503

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 ...[more]

PMID: 18958202

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Project description:Declines in cognitive functioning are commonly experienced with aging, yet there is wide variation in the nature and extent of these changes. Previous research has shown associations between the frequency of engaging in stimulating cognitive activities and performance on cognitive tests. However, it is not known whether it is important to increase the amount of cognitive activity as one gets older in order to curtail cognitive declines. We examined cognitive activities and cognition in a national sample of 2,130 community-dwelling middle-aged and older adults from the Midlife in the United States longitudinal study. Participants completed cognitive assessments of episodic memory (EM) and executive functioning (EF) on two occasions, ~9 years apart. At the first assessment, participants ranged in age between 33 and 83 years (M = 55.76, SD = 11.09), with 56.1% women. Multilevel models were tested to examine educational level and change in cognitive activity as predictors of change in EM and EF, controlling for initial level of cognitive activity and key correlates of cognitive decline. Results indicated that increases in cognitive activity were important over and above earlier levels of cognitive activity for reducing declines in EF. Further analysis also showed differential results by educational level. Increased cognitive activity was not associated with changes in EF among individuals with a college degree. In contrast, individuals without a college degree who increased their cognitive activity showed significantly less decline in EF compared to those without a college degree who decreased or maintained their cognitive activity across the 9 years. Thus, the results suggest that increased engagement in cognitive activity makes more of a difference for EF declines among those without a college degree. The results have particular relevance given that aging-related changes in domains such as work status, health, or social relationships can lead to reductions in stimulating cognitive activities. The findings emphasize the importance of increasing cognitive activities especially among those with lower educational attainment.

Dataset Information

Human aging magnifies genetic effects on executive functioning and working memory.

Publications

Human aging magnifies genetic effects on executive functioning and working memory.

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