BDNF val66met polymorphism affects aging of multiple types of memory

Abstract

The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived 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).

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults

“…16 Although our sample size is small, our data do not reflect a sample-specific effect, as they corroborate previous findings associating the BDNF Met allele and memory impairments in older adults. 9,29 Given the complexity of neuronal processes underlying the BDNF Val66Met polymorphism and memory performance in elderly, we believe that our findings are in accordance with the modulation hypothesis proposed by a previous study. 37 According to the authors, this nonlinear hypothesis assumes that the magnitude of the genetic predisposition for poorer cognition performance conditioned by the BDNF Met allele could be increased in the elderly, especially when chemical and structural brain resources are declining with the life-span.…”

Motion‐related artifacts in structural brain images revealed with independent estimates of in‐scanner head motion

“…This subsample includes at least 30 participants in each decade of the sampled age range and represents individuals who performed the complete series of seven fMRI runs [e.g., Chan et al, 2014; Kennedy et al, 2015; Park et al, 2012, 2013; see Fig. 1].…”

BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention

“…Initial cross-sectional studies on this polymorphism found that in younger adults, Met carriership was associated with worse episodic memory as measured by the Wechsler Memory Scale and an fMRI declarative memory paradigm. 14,19 More recently, a study in an aging population 18 (mean age 56 years) demonstrated cross-sectionally that Met carriers performed worse in both item memory and prospective memory with advancing age compared with Val/Val homozygotes. Item memory was assessed with the California Verbal Learning Test, 18 a psychometric measure similar to the RAVLT, which comprises our verbal learning and memory measure.…”

“…14,19 More recently, a study in an aging population 18 (mean age 56 years) demonstrated cross-sectionally that Met carriers performed worse in both item memory and prospective memory with advancing age compared with Val/Val homozygotes. Item memory was assessed with the California Verbal Learning Test, 18 a psychometric measure similar to the RAVLT, which comprises our verbal learning and memory measure. Another crosssectional study 17 showed that in addition to memory, processing speed was reduced in Met carriers compared to Val/Val homozygotes (mean age 63 years).…”

“…Carriage of 1 or 2 Met alleles is associated with lower BDNF production, 14 decreased hippocampal volume, 15 and cognitive decline. [16][17][18][19] However, null 20,21 and opposite findings 22,23 have been documented, making the relationship between BDNF and cognition in aging populations unclear.…”