Abstract
The concept of cognitive reserve (CR) has been proposed to account for observed discrepancies between pathology and its clinical manifestation due to underlying differences in brain structure and function. In 433 healthy older adults participating in the Tasmanian Healthy Brain Project, we investigated whether common polymorphic variations in apolipoprotein E (APOE) or brain-derived neurotrophic factor (BDNF) influenced the association between CR contributors and cognitive function in older adults. We show that BDNF Val66Met moderates the association between CR and executive function. CR accounted for 8.5% of the variance in executive function in BDNF Val homozygotes, but CR was a nonsignificant predictor in BDNF Met carriers. APOE polymorphisms were not linked to the influence of CR on cognitive function. This result implicates BDNF in having an important role in capacity for building or accessing CR.
Highlights
Observations of significant heterogeneity in the clinical manifestation of underlying brain pathology has led to the development of the concept of cognitive reserve (CR).[1]
Simple slopes analysis was conducted in order to determine the basis of the moderation effect of brain-derived neurotrophic factor (BDNF) polymorphism on the conditional effect between CR and executive function, and to determine whether the slopes statistically differed from zero for BDNF Met carriers and noncarriers, separately. These analyses indicate that a significant positive relationship between CR and executive function was identified in BDNF Val homozygotes (β = 0.13, t = 5.56, s.e. = 0.02, Po 0.01), but was not evident in BDNF Met carriers (β = 0.05, t = 1.52, s.e. = 0.03, P = 0.13)
The present study was designed to investigate whether a composite measure of CR was associated with healthy cognitive function, either independently or through an interaction with genetic apolipoprotein E (APOE)/BDNF Val66Met polymorphic data, in participants of the Tasmanian Healthy Brain Project (THBP)
Summary
Observations of significant heterogeneity in the clinical manifestation of underlying brain pathology has led to the development of the concept of cognitive reserve (CR).[1]. Epidemiological evidence further supports the notion of CR by demonstrating consistent associations between lifestyle characterized by intellectual and social engagement and slower cognitive decline.[5] In older persons, functional magnetic resonance imaging studies of neural networks suggest that differences in functionally connected regions in persons with high CR may enhance the compensatory capacity of individuals in the face of both normal and pathological brain aging.[6] Alzheimer’s disease (AD) patients with higher educational and occupational attainment have more rapid cognitive decline than those with lower attainment, consistent with the idea that at a given common level of severity, underlying AD pathology is more advanced in patients with more CR.[7] That individuals with higher CR display greater resistance to the effects of neuropathology is likely due to induced cortical plasticity caused by a prolonged mismatch between functional supply and task demands,[8] resulting in more flexible and denser neural networks.[9] As adult cognitive function and cognitive aging show significant heritability,[10] research examining the interaction between genes and CR proxies is justified. The most likely candidate genes for CR are those that interact with environmental factors to induce effects on cognitive functions.[11]
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