Altered white matter architecture in BDNF Met carriers

Brain-derived neurotrophic factor (BDNF) modulates the pruning of synaptically-silent axonal arbors. The Met allele of the BDNF gene is associated with a reduction in the neurotrophin's activity-dependent release. We used di ffusion-weighted imaging to construct structural brain networks for 36 healthy subjects with known BDNF genotypes. Through permutation testing we discovered clear di fferences in connection strength between subjects carrying the Met allele and those homozygotic for the Val allele. We trained a Gaussian process classi fier capable of identifying the subjects' allelic group with 86% accuracy and high predictive value. In Met carriers structural connectivity was greatly increased throughout the forebrain, particularly in connections corresponding to the anterior and superior corona radiata as well as corticothalamic and corticospinal projections from the sensorimotor, premotor and prefrontal portions of the internal capsule. Interhemispheric connectivity was also increased via the corpus callosum and anterior commissure, and extremely high connectivity values were found between inferior medial frontal polar regions via the anterior forceps. We propose that the decreased availability of BDNF leads to de cifits in axonal maintenance in carriers of the Met allele, and that this produces mesoscale changes in white matter architecture

A Meta-analysis of Heritability of Cognitive Aging: Minding the “Missing Heritability” Gap

The etiologies underlying variation in adult cognitive performance and cognitive aging have enjoyed much attention in the literature, but much of that attention has focused on broad factors, principally general cognitive ability. The current review provides meta-analyses of age trends in heritability of specific cognitive abilities and considers the profile of genetic and environmental factors contributing to cognitive aging to address the ‘missing heritability’ issue. Our findings, based upon evaluating 27 reports in the literature, suggest that verbal ability demonstrated declining heritability after age 60, as did spatial ability and perceptual speed more modestly. Trends for general memory, working memory, and spatial ability generally indicated stability, or small increases in heritability in mid-life. Equivocal results were found for executive function. A second meta-analysis then considered the gap between twin-based versus SNP-based heritability derived from population-based GWAS studies. Specifically, we considered twin correlation ratios to agnostically re-evaluate biometrical models across age and by cognitive domain. Results modestly suggest that nonadditive genetic variance may become increasingly important with age, especially for verbal ability. If so, this would support arguments that lower SNP-based heritability estimates result in part from uncaptured non-additive influences (e.g., dominance, gene-gene interactions), and possibly gene-environment (GE) correlations. Moreover, consistent with longitudinal twin studies of aging, as rearing environment becomes a distal factor, increasing genetic variance may result in part from nonadditive genetic influences or possible GE correlations. Sensitivity to life course dynamics is crucial to understanding etiological contributions to adult cognitive performance and cognitive aging

Effects of BDNF polymorphism and physical activity on episodic memory in the elderly: a cross sectional study

International audienceBackground:The brain-derived neurotrophic factor (BDNF) concentration is highest in the hippocampus comparedwith that in other brain structures and affects episodic memory, a cognitive function that is impaired in olderadults. According to the neurotrophic hypothesis, BDNF released during physical activity enhances brain plasticity andconsequently brain health. However, even if the physical activity level is involved in the secretion of neurotrophin, thisprotein is also under the control of a specific gene. The aim of the present study was to examine the effect of theinteraction between physical activity and BDNF Val66Met(rs6265), a genetic polymorphism, on episodic memory.Methods:Two hundred and five volunteers aged 55 and older with a Mini Mental State Examination score≥24participated in this study. Four groups of participants were established according to their physical activity level andpolymorphism BDNF profile (Active Val homozygous, Inactive Val homozygous, Active Met carriers, Inactive Met carriers).Episodic memory was evaluated based on the delayed recall of the Logical Memory test of the MEM III battery.Results:As expected, the physical activity level interacted with BDNF polymorphism to affect episodic memoryperformance (p< .05). The active Val homozygous participants significantly outperformed the active Met carriers andinactive Val homozygous participants.Conclusion:This study clearly demonstrates an interaction between physical activity andBDNF Val66Metpolymorphismthat affects episodic memory in the elderly and confirms that physical activity contributes to the neurotrophic mechanismimplicated in cognitive health. The interaction shows that only participants with Val/Val polymorphism benefited fromphysical activit