Original Research Article
Human aging magnifies genetic effects on executive functioning and working memory
Irene E. Nagel 1, 2, Christian Chicherio 1, Shu-Chen Li 1, 2, Timo von Oertzen 1, Thomas Sander 3, Arno Villringer 2, 4, 5, Hauke R. Heekeren 1, 2, 4, 5, Lars Bäckman 1, 2, 6 and Ulman Lindenberger 1, 2*
1 Center for Lifespan Psychology, Max Planck Institute for Human Development, Germany
2 Berlin Neuroimaging Center, Germany
3 Max Delbrück Center for Molecular Medicine, Germany
4 Department of Cognitive Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Germany
5 Department of Neurology, Charité , University Medicine, Germany
6 Aging Research Center, Karolinska Institute, Sweden
2 Berlin Neuroimaging Center, Germany
3 Max Delbrück Center for Molecular Medicine, Germany
4 Department of Cognitive Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Germany
5 Department of Neurology, Charité , University Medicine, Germany
6 Aging Research Center, Karolinska Institute, Sweden
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
Copyright: © 2008 Nagel, Chicherio, Li, von Oertzen, Sander, Villringer, Heekeren, Bäckman and Lindenberger. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
*Correspondence: Ulman Lindenberger, Center for Lifespan Psychology, Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany. e-mail: lindenberger@mpib-berlin.mpg.de
Citation: Nagel IE, Chicherio C, Li S, von Oertzen T, Sander T, Villringer A, Heekeren HR, Bäckman L and Lindenberger U (2008) Human aging magnifies genetic effects on executive functioning and working memory. Front. Hum. Neurosci. (2008) 2:1. doi:10.3389/neuro.09.001.2008
Received: 03 March 2008; paper pending published: 25 March 2008; accepted: 19 April 2008; published online: 06 May 2008.
Edited by:
Kenneth Hugdahl, University of Bergen, Norway
Reviewed by:
Nils I. Landro, University of Oslo, Norway
Kenneth Hugdahl, University of Bergen, Norway
Kenneth Hugdahl, University of Bergen, Norway
*Correspondence: Ulman Lindenberger, Center for Lifespan Psychology, Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany. e-mail: lindenberger@mpib-berlin.mpg.de
