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

Paolo Ghisletta,Denis Gerstorf,Ulman Lindenberger,Lars Bertram,Tian Liu,Andreas Markus Brandmaier,Lars Bäckman

doi:10.1037/a0035201

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 = 123, 34%) showed steeper linear decline than Val homozygotes (n = 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.

Highlights

ObjectivesUsing a candidate gene approach, we focused on the brain-derived neurotrophic factor (BDNF) gene and its Val66Met single-nucleotide polymorphisms (SNPs) to investigate its association with change in cognitive performance in the Berlin Aging Study (BASE; Baltes & Mayer, 1999; Lindenberger, Smith, Mayer, & GHISLETTA ET AL.Baltes, 2010)
We investigated whether a common Val66Met missense polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with individual differences in cognitive decline in old age
Using a candidate gene approach, we focused on the BDNF gene and its Val66Met single-nucleotide polymorphisms (SNPs) to investigate its association with change in cognitive performance in the Berlin Aging Study

Summary

Objectives

Using a candidate gene approach, we focused on the BDNF gene and its Val66Met SNP to investigate its association with change in cognitive performance in the Berlin Aging Study (BASE; Baltes & Mayer, 1999; Lindenberger, Smith, Mayer, & GHISLETTA ET AL.Baltes, 2010). Using a candidate gene approach, we focused on the BDNF gene and its Val66Met SNP to investigate its association with change in cognitive performance in the Berlin Aging Study Characteristics about change are estimated at the latent level, thereby isolating reliable from residual variance in the task, which maximizes the power to detect interindividual variability in change and, subsequently, effects of possible predictors of interindividual variability in change. The novel features of this study are a relatively large sample size, a high number of repeated measures, a relatively long epoch of observation, the statistical control of multiple potential age confounds, and the use of a statistical method that accounts for residual variance

Methods

Results

Conclusion