Apolipoprotein E genotype (APOE) is the predominant risk modifier for Alzheimer’s disease. Empirical evidence published by us and others support the hypothesis that APOE modifies the response to dietary factors, based on evolutionary adaptation. These findings warrant replication. Our aim is to estimate the effect of compositional dietary factors on cognitive health outcomes and mortality. Primarily, we will dichotomize APOE 3/4 and 4/4 (APOE34/44) versus non-APOE34/44. We will also examine the six common genotypes separately, to explore the hypothesis that effect modification will follow a gradient: APOE22-23-24-33-34-44.
Primary exposure: Unprocessed meat (by weight, standardized for total energy intake). Secondary exposures: Total meat and ratios between meat types. Other food groups (egg, fish, seafood, tubers, nuts, vegetables, legumes, cereals, dairy etc.); Macronutrient parameters: Carbohydrates/Fat (log-ratio), and protein E(%); Micronutrient parameters: vitamin B12 etc..; Metabolic biomarkers
Future directions of the project may include other health and disease outcomes. The exposures of interest may be extended to medications, particularly lipid lowering drugs, hypertensives, and diabetes drugs. These extensions will typically target the overall research question of APOE as an effect modifier, potentially extending to other genes of interest.