Abstract
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.
Highlights
Old age is often accompanied by cognitive impairment with the largest deficits on executive control tasks that are reliant on prefrontal cortex function (Hedden and Gabrieli, 2004)
We employed a one-way ANOVA to examine whether the COMT single nucleotide polymorphism (SNP) was related to performance on the Mini-Mental Status Examination (MMSE) task – a general and widely used measure to test for possible dementia and impaired cognitive function
In this study we examined whether the brainderived neurotrophic factor (BDNF) or COMT polymorphisms could explain variation in the trajectory of cognitive decline over a 10-year span in older adults
Summary
Old age is often accompanied by cognitive impairment with the largest deficits on executive control tasks that are reliant on prefrontal cortex function (Hedden and Gabrieli, 2004). Evidence from both humans and non-human animals suggests that some cognitive deficits observed in old age could be related to disruptions in the dopaminergic and neurotrophic systems (Bäckman et al, 2006; Pang and Lu, 2004). Some studies, including a recent meta-analysis have reported that
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