AUTHOR=Nagel Irene E., Chicherio Christian , Li Shu-Chen , Von Oertzen Timo , Sander Thomas , Villringer Arno , Heekeren Hauke R., Bäckman Lars , Lindenberger Ulman 

TITLE=Human aging magnifies genetic effects on executive functioning and working memory

JOURNAL=Frontiers in Human Neuroscience

VOLUME=2

YEAR=2008

URL=https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/neuro.09.001.2008

DOI=10.3389/neuro.09.001.2008

ISSN=1662-5161

ABSTRACT=<p>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 (<abbrev>COMT</abbrev>) enzyme, which degrades dopamine (<abbrev>DA</abbrev>) in prefrontal cortex (<abbrev>PFC</abbrev>), and the other influencing the brain-derived neurotrophic factor (<abbrev>BDNF</abbrev>) protein. In two tasks (Wisconsin Card Sorting and spatial working memory), we find that effects of <abbrev>COMT</abbrev> genotype on cognitive performance are magnified in old age and modulated by <abbrev>BDNF</abbrev> genotype. Older <abbrev>COMT</abbrev> Val homozygotes showed particularly low levels of performance if they were also <abbrev>BDNF</abbrev> Met carriers. The age-associated magnification of <abbrev>COMT</abbrev> gene effects provides novel information on the inverted U-shaped relation linking dopaminergic neuromodulation in <abbrev>PFC</abbrev> to cognitive performance. The modulation of <abbrev>COMT</abbrev> effects by <abbrev>BDNF</abbrev> extends recent evidence of close interactions between frontal and medial-temporal circuitries in executive functioning and working memory.</p>