Environmental and genetic contributors to cognitive reserve

An individual’s rate of age-related cognitive decline and risk for later-life dementia is influenced by environmental and genetic factors. One protective environmental factor that may mitigate cognitive decline is cognitive reserve (CR) and is generated by participation in tasks that involve complex cognitive engagement. Two genes that may influence CR through their associations with synaptic plasticity are apolipoprotein E (APOE) and brain-derived neurotrophic factor (BDNF). Participants from the on-going Tasmanian Healthy Brain Project, a longitudinal investigation into whether an intervention of later-life tertiary education increases CR, contributed to the data analysed in this thesis. It was aimed: to develop two operational measures of CR; to quantify the cognitive implications of variation in APOE and BDNF Val66Met; and to detect genetic interactions with CR. Comprehensive neuropsychological assessments were conducted as part of the baseline testing for Tasmanian Healthy Brain Project participants. APOE and BDNF Val66Met polymorphisms were determined through analysis of saliva samples. The statistical analyses yielded three main results. First, factor analysis was successful in identifying latent variables in both prior and current models of CR. Second, while variation in APOE or BDNF did not produce significant main effects in any assessed cognitive domain, an APOE x BDNF interaction was present in episodic memory function. Third, BDNF moderated the association between CR and executive function, with a significantly reduced association between the variables present in BDNF Met carriers. Overall, this investigation developed a method of assessing CR that can provide a comprehensive estimate of an individual’s CR and furthered knowledge on the effect single genes exert on healthy cognitive function. The most important finding to emerge was a CR x BDNF interaction in cognitive function, which suggests that CR-based interventions aimed at delaying dementia onset may have a higher efficacy in BDNF Val homozygotes than in BDNF Met carriers