Abstract
Project Description: Identification of lifestyle and dietary modifications which prevent or delay cognitive decline and Alzheimer's disease (AD) onset would confer significant social and economic benefit. However, there is a relative lack of large-scale investigations of lifestyle-related factors impacting cognitive decline and AD-related pathology. There is a critical need for longitudinal data collected from well-characterised ageing cohorts, and assessment of lifestyle in the context of Apolipoprotein E (APOE) genotype to facilitate development of strategies tailored to the needs of APOE ε4 allele carriers for whom prognosis is currently poorest. We report on dietary and physical activity data collected from healthy control participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. The Cancer Council of Victoria Food Frequency Questionnaire was used to evaluate dietary pattern adherence (n=527), and physical activity levels were determined by self-report using the International Physical Activity Questionnaire (n=124). These measures were subsequently analysed in conjunction with APOE genotype, Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, neuroimaging and comprehensive neuropsychological assessment data. Linear mixed model analyses revealed that higher baseline adherence to a 'healthy' Mediterranean diet pattern was associated with reduced decline in the executive function cognitive domain after 36 months amongst APOE Ɛ4 allele carriers (p<0.01). Conversely, higher adherence to an 'unhealthy' western diet pattern at baseline was associated with greater decline after 36 months in the visuospatial cognitive domain in APOE Ɛ4 allele non-carriers (p<0.01).Hierarchical regressions demonstrated an association between higher levels of physical activity and larger hippocampal volume as determined by Magnetic Resonance Imaging (β=0.19;p<0.05). When stratified by BDNF Val66Met polymorphism and APOE Ɛ4 allele, physical activity was associated with larger hippocampal and temporal lobe volumes in the Val/Val homozygote group for the BDNF Val66Met polymorphism, and the relationship between physical activity and temporal lobe volume amongst Val/Val homozygotes was dependent on APOE ε4 allele carriage (β=-0.38;p<0.05). We have previously reported that brain and blood Aβ levels are modulated by physical activity by APOE genotype-dependent mechanisms. Taken together, our results are suggestive of differential effects of lifestyle factors on aspects of cognitive decline and AD-related pathology that are contingent on APOE Ɛ4 allele carriage.