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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.

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