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Original Research ARTICLE

Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms

1
Psychology Department, University of Illinois at Urbana-Champaign, Champaign, IL, USA
2
Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA
3
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
4
School of Integrative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
5
Entomology Department, University of Illinois at Urbana-Champaign, Urbana, IL, USA
Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age.
Keywords:
BDNF, COMT, aging, task-switching, cognition, executive control, longitudinal
Citation:
Erickson KI, Kim JS, Suever BL, Voss MW, Francis BM and Kramer AF (2008). Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms. Front. Hum. Neurosci. 2:11. doi: 10.3389/neuro.09.011.2008
Received:
23 June 2008;
 Paper pending published:
18 August 2008;
Accepted:
31 August 2008;
 Published online:
23 September 2008.

Edited by:

William J. Jagust, University of California Berkeley, USA

Reviewed by:

Cheryl Grady, University of Toronto, Canada
Roshan Cools, University of Cambridge, UK
Copyright:
© 2008 Erickson, Kim, Suever, Voss, Francis and Kramer. 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:
Kirk I. Erickson, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N. Matthews Ave., Urbana, IL 61801, USA. e-mail: kiericks@uiuc.edu

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