The Val/Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene predicts decline in perceptual speed in older adults.

Abstract

The brain-derived neurotrophic factor (BDNF) promotes activity-dependent synaptic plasticity, and contributes to learning and memory. We investigated whether a common Val66Met missense polymorphism (rs6265) of the BDNF gene is associated with individual differences in cognitive decline (marked by perceptual speed) in old age. A total of 376 participants of the Berlin Aging Study, with a mean age of 83.9 years at first occasion, were assessed longitudinally up to 11 times across more than 13 years on the Digit-Letter task. Met carriers (n ϭ 123, 34%) showed steeper linear decline than Val homozygotes (n ϭ 239, 66%); the corresponding contrast explained 2.20% of the variance in change in the entire sample, and 3.41% after excluding individuals at risk for dementia. These effects were not moderated by sex or socioeconomic status. Results are consistent with the hypothesis that normal aging magnifies the effects of common genetic variation on cognitive functioning. Keywords: cognitive decline, BDNF Val/Met polymorphism, Berlin Aging StudyIn recent years, the field of cognitive aging has enriched its explanatory scope by paying increasing attention to the effects of genetic and epigenetic variation on individual differences in cognitive performance. Two broad approaches can be distinguished

Aging-related magnification of genetic effects on cognitive and brain integrity

“…Importantly, age-comparative studies have reported magnified effects of BDNF in old age, with older Val homozygotes showing better episodic memory compared with older Met carriers [36]. In addition, in line with the resource-modulation hypothesis, longitudinal data from a sample of older adults aged 70 to 103 years demonstrate exacerbated decline in perceptual speed across 13 years for Met carriers [37], an effect that remained after excluding prodromal dementia cases ( Figure 3A). Similarly, pilots carrying the Met allele (aged 40-69 years) declined disproportionately across 2 years in flight-simulator performance, presumably reflecting executive functioning [38].…”

“…The y-axis indicates the total number of correct responses after 3 minutes. Adapted from [37] with permission from American Psychological Association. Interaction between age and BDNF, reflecting (B) lower hippocampal activity during retrieval of episodic memories, (C) smaller hippocampal volumes, and (D) lower white-matter integrity in the splenium for older BDNF Met carriers.…”

The Effects of BDNF Val66Met Gene Polymorphism on Serum BDNF and Cognitive Function in Methamphetamine-Dependent Patients and Normal Controls

“…Although it has been reported that Val66Met could predict decline in perceptual speed and poorer working memory performance in older adults 27,28 and visuospatial/constructional abilities significantly differed by Val66Met genotype in both schizophrenic patients and healthy controls, 29 our results were consistent with a meta-analysis that did not establish significant genetic associations between the Val66Met polymorphism and cognitive function except for the executive function. 30 There are several reasons to explain the negative and inconsistent results: In this study, we found a significant genotype  diagnosis effect on visuospatial/constructional, indicating the Val66Met variant may have a specific role in visuospatial function among methamphetamine addict.…”

Genetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging

“…Adult age-comparative studies have reported magnified effects of the BDNF polymorphism in old age for episodic memory , with older Val homozygotes performing better on backward serial recall. Also in line with the resource modulation hypothesis, longitudinal data demonstrate exacerbated decline in perceptual speed across 13 years among BDNF Met carriers (Ghisletta et al 2014), an effect that remained after excluding prodromal dementia cases. Similarly, Sanchez et al (2011) reported that pilots carrying the Met allele (aged 40-69 years) declined disproportionately in flight-simulator performance, presumably reflecting executive functioning.…”