AbstractBackgroundIntake of dietary fat has been linked with cognition. Apolipoprotein E plays a critical role in lipid metabolism; however, the potential interaction between ApoE ε4 carrier and dietary fat on cognition is not fully understood. We aim to examine the association of types of dietary fat and their relation to cognitive decline among those with and without the ApoE ε4 allele.MethodThe study included 3,528 participants from the Chicago Health and Aging Project (62% African Americans, 63% female). Global cognition was assessed using a composite score of episodic memory, perceptual speed, MMSE; and diet using a 139‐item food frequency questionnaire. ApoE genotype was assessed by hME Sequenom mass‐array platform. Longitudinal mixed effect regression models were used to examine the association of dietary fat and the ApoE ε4 allele with cognitive decline, adjusting for age, sex, education, smoking status, and calorie intake.ResultAmong varying types of dietary fat, including saturated fat (SFA), monounsaturated fat, and polyunsaturated fat, we found that a higher intake of SFA was associated with faster cognitive decline (p for trend 0.0274). Per 5% increase in calorie from SFA was associated with a 15% faster cognitive decline (β = ‐0.0064, p = 0.04). Participants in the highest quintile of intakes of SFA had a 34% faster cognitive decline than those in the lowest quintile (β = ‐0.0125, p = 0.0095).In those with ApoE ε4 allele, per 5% increase in calorie from SFA was association with a 21% faster decline (β = ‐0.0197, p = 0.0038). Among participants with ApoE ε4 allele, individuals in the highest quintile of intakes of SFA had a 45% faster cognitive decline compared to those in the lowest quintile of intake (β = ‐0.0372, p = 0.0003). Higher SFA was not associated with cognitive decline among those without the ApoE ε4 allele nor other types of dietary fat.ConclusionOur study found a significant association of saturated fat with faster cognitive decline among those with the ApoE4 allele. Higher intake of saturated fat among the ApoE4 carriers might lead to significantly higher risk of cognitive decline in old age.