The BDNF Val66Met polymorphism moderates the relationship between cognitive reserve and executive function

Ward, David; Summers, Mathew J.; Saunders, Nichole L.; Ritchie, Karen; Summers, Jeffery J.; Vickers, James C. · 2015 · OpenAlex-citations

DOI: 10.1038/tp.2015.82

archive: archived pipeline: cataloged verified

Get this paper ↗ (DOI — opens at the source; we link to it, we don't host it)

Summary

This study investigates whether genetic variations in apolipoprotein E (APOE) or brain-derived neurotrophic factor (BDNF) moderate the relationship between cognitive reserve (CR) and cognitive function in healthy older adults. The concept of CR explains discrepancies between brain pathology and clinical manifestation, suggesting that biological and environmental factors influence an individual's capacity to compensate for neural decline. While APOE is a known risk factor for Alzheimer’s disease, its role in healthy cognition is less clear. BDNF, crucial for synaptic plasticity, contains the Val66Met polymorphism, which affects activity-dependent secretion. The authors hypothesized that carriers of detrimental alleles (APOE ε4 or BDNF Met) would show a reduced influence of CR on cognitive performance compared to noncarriers. The research utilized baseline data from 433 healthy older adults (aged 50–79) participating in the Tasmanian Healthy Brain Project. Participants were screened to exclude those with conditions affecting cognitive function. CR was quantified using a composite score derived from lifetime education, occupational attainment, estimated premorbid intelligence, and participation in cognitively stimulating leisure activities. Cognitive function was assessed across four domains: episodic memory, working memory, executive function, and language processing. Genotyping for APOE and BDNF Val66Met was performed via PCR. Statistical analyses employed PROCESS macro for moderation analysis, testing the interaction between CR and genetic status on cognitive outcomes while controlling for age and gender. The results confirmed that higher CR was significantly associated with better performance across all four cognitive domains. However, only the BDNF Val66Met polymorphism significantly moderated this relationship. Specifically, BDNF moderated the association between CR and executive function. In BDNF Val homozygotes, CR accounted for 8.6% of the variance in executive function, showing a significant positive relationship. In contrast, for BDNF Met carriers, CR was a nonsignificant predictor, accounting for only 1.5% of the variance. No significant moderation effects were found for APOE, nor were there significant interactions for other cognitive domains. These findings indicate that BDNF plays a critical role in the capacity to build or access cognitive reserve, particularly regarding executive function. The study suggests that the biochemical mechanisms underlying synaptic plasticity, influenced by the BDNF Val66Met polymorphism, determine how effectively environmental and educational factors translate into cognitive resilience. This implies that individuals with the Met allele may have a reduced ability to leverage cognitive reserve to maintain executive function, highlighting the importance of genetic factors in the development of CR prior to the onset of clinical symptoms.

Provenance

The full processing record for this entry. Every stage of this paper's journey through the pipeline is logged — what ran, with which tool and model, how many attempts it took, and when it last completed.

Summary generated by qwen3.6-27b-prismaquant on 2026-06-26; verification: verified.

Topics

Ranked by relevance to this paper. Hover a topic for its definition.

• cognitive capacity variation