BDNF Val66Met polymorphism and memory performance in older adults: the Met carrier effect is more complex than previously thought (original) (raw)
Related papers
BDNF val66met polymorphism affects aging of multiple types of memory
Brain Research, 2014
The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brainderived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age x BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (p < .07) toward poorer associative memory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory -in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory).
Effect of BDNF val66met polymorphism on declarative memory and its neural substrate: A meta-analysis
Neuroscience & Biobehavioral Reviews, 2012
Brain derived neurotrophic factor (BDNF) is a critical component of the molecular mechanism of memory formation. Variation in the BDNF gene, particularly the rs6265 (val 66 met) single nucleotide polymorphism (SNP), has been linked to variability in human memory performance and to both the structure and physiological response of the hippocampus, which plays a central role in memory processing. However, these effects have not been consistently reported, which may reflect the modest size of the samples studied to date. Employing a meta-analytic approach, we examined the effect of the BDNF val 66 met polymorphism on human memory (5922 subjects) and hippocampal structure (2985 subjects) and physiology (362 subjects). Our results suggest that variations in the rs6265 SNP of the BDNF gene have a significant effect on memory performance, and on both the structure and physiology of the hippocampus, with carriers of the met allele being adversely affected. These results underscore the role of BDNF in moderating variability between individuals in human memory performance and in mediating some of the neurocognitive impairments underlying neuropsychiatric disorders.
Psicológica, 2023
The polymorphisms (C270T) and Val66Met of the BDNF gene are related to diverse cognitive processes in neurological and psychiatric conditions. But little is known about its relations with cognitive processes in healthy people. The present study explored the relationship of the C270T and Val66Met polymorphisms with implicit memory (semantic and perceptual priming tasks), semantic explicit memory (lexical selection), and episodic explicit memory (free recall). In total, 135 healthy volunteers between 20 and 60 years of age (M = 27.94, SD = 11.04), 92 women (M = 27.36, SD = 11.32), and 42 men (M = 29.21, SD = 10.42), participated in the study. One hundred and three of them completed the genetic study of C270T (36 males and 67 females), and 123 completed the Val66Met (38 males and 85 females). Results regarding ValMet polymorphism showed lower scores for MetMet in free recall. In relation to C270T, TT polymorphism performed better in the visual priming task than CT. The potential value as biomarkers of memory of these polymorphisms is discussed.
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2010
Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampal synaptic plasticity and long-term potentiation. A valine (Val) to methionine (Met) substitution in the BDNF gene (Val66Met) has been associated with episodic memory performance. This study aimed at fine-mapping the genomic region harbouring BDNF and the adjacent gene, BDNFOS, in order to identify other possible memory-related gene variants. Healthy young Swiss adults (n=333) underwent a verbal memory free-recall task which used words with both neutral and emotional content. Genetic variability of the BDNF and BDNFOS region was covered by analysing 55 single nucleotide polymorphisms (SNPs). Among all examined SNPs, the non-synonymous Val66Met SNP rs6265 showed the highest significant level of association with memory performance for words with emotional content. Recall performance for neutral words was unrelated to the analysed SNPs. Our results support a role for the Val66Met BDNF polymorphism in episodic memory and suggest a modulatory influence of emotional valence.(Received February 04 2010)(Reviewed March 03 2010)(Revised April 01 2010)(Accepted April 10 2010)(Online publication May 19 2010)
Genes, Brain and Behavior, 2008
A functional brain-derived neurotrophic factor (BDNF) gene polymorphism (Val66Met) that alters activitydependent secretion has previously been reported to influence cognitive functioning. A large proportion of these reports suggest that the Met allele, which results in reduced secretion of BDNF, impairs long-term memory as a direct consequence of its influence on hippocampal function but has little influence on working memory. In contrast, other studies have found that the Met allele can also play a protective role in certain neurological conditions and is associated with improved non-verbal reasoning skills in the elderly suggesting effects that appear disease, domain and age specific. We have investigated six haplotype-tagging single nucleotide polymorphisms (SNPs) using a cohort of 722 elderly individuals who have completed cognitive tests that measured the domains of fluid intelligence, processing speed and memory. We found that the presence of the Met allele reduced cognitive performance on all cognitive tests. This reached nominal significance for tests of processing speed (P 5 0.001), delayed recall (P 5 0.037) and general intelligence (g) (P 5 0.008). No association was observed between cognitive tests and any other SNPs once the Val66Met was adjusted for. Our results support initial findings that the Met allele is associated with reduced cognitive functioning. We found no evidence that the Met allele plays a protective role in older non-demented individuals. Magnetic resonance imaging data collected from a subgroup of 61 volunteers showed that the left and right hippocampus were 5.0% and 3.9% smaller, respectively, in those possessing the Met allele, although only a non-significant trend was observed.
Brain-derived neurotrophic factor Val66Met polymorphism, human memory, and synaptic neuroplasticity
Wiley interdisciplinary reviews. Cognitive science, 2015
Some people have much better memory than others, and there is compelling evidence that a considerable proportion of this variation in memory ability is genetically inherited. A form of synaptic plasticity known as long-term potentiation (LTP) is the principal candidate mechanism underlying memory formation in neural circuits, and it might be expected, therefore, that a genetic influence on the degree of LTP might in turn influence memory abilities. Of the genetic variations thought to significantly influence mnemonic ability in humans, the most likely to have its effect via LTP is a single nucleotide polymorphism affecting brain-derived neurotrophic factor [BDNF (Val66Met)]. However, although it is likely that BDNF influences memory via a modulation of acute plasticity (i.e., LTP), BDNF also has considerable influence on structural development of neural systems. Thus, the influence of BDNF (Val66Met) on mnemonic performance via influences of brain structure as well as function must ...
Background: The brain-derived neurotrophic factor (BDNF) concentration is highest in the hippocampus compared with that in other brain structures and affects episodic memory, a cognitive function that is impaired in older adults. According to the neurotrophic hypothesis, BDNF released during physical activity enhances brain plasticity and consequently brain health. However, even if the physical activity level is involved in the secretion of neurotrophin, this protein is also under the control of a specific gene. The aim of the present study was to examine the effect of the interaction 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 ≥ 24 participated in this study. Four groups of participants were established according to their physical activity level and polymorphism 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.