Dietary fats and the APOE-e4 risk allele in relation to cognitive decline: a longitudinal investigation in a biracial population sample

Xiaoran Liu; Todd Beck; Klodian Dhana; Christy C Tangney; Pankaja Desai; Kristin Krueger; Denis A Evans; Kumar B Rajan

doi:10.1016/j.jnha.2024.100211

Dietary fats and the APOE-e4 risk allele in relation to cognitive decline: a longitudinal investigation in a biracial population sample

J Nutr Health Aging. 2024 Mar 19;28(5):100211. doi: 10.1016/j.jnha.2024.100211. Online ahead of print.

Authors

Xiaoran Liu¹, Todd Beck², Klodian Dhana², Christy C Tangney³, Pankaja Desai², Kristin Krueger², Denis A Evans², Kumar B Rajan²

Affiliations

¹ Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL, USA; Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA. Electronic address: Xiaoran_Liu@rush.edu.
² Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL, USA; Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
³ Department of Clinical Nutrition & Preventive Medicine, Rush University Medical Center, Chicago, IL, USA.

PMID: 38507884
DOI: 10.1016/j.jnha.2024.100211

Abstract

Background: APOE-e4 is the strongest genetic risk factor for Alzheimer's disease. However, the influence of APOE-e4 on dietary fat intake and cognition has not been investigated.

Objective: We aim to examine the association of types of dietary fat and their association to cognitive decline among those with and without the APOE-e4 allele.

Methods: The study included 3,360 Chicago Health and Aging Project (CHAP) participants from four Southside Chicago communities. Global cognition was assessed using a composite score of episodic memory, perceptual speed, MMSE, and diet using a 144-item food frequency questionnaire. APOE genotype was assessed by the hME Sequenom mass-array platform. Longitudinal mixed-effect regression models were used to examine the association of dietary fat and the APOE-e4 allele with cognitive decline, adjusted for age, sex, education, smoking status, and calorie intake.

Results: The present study involved 3,360 participants with a mean age of 74 at baseline, 62% African Americans, 63% females, and a mean follow-up of 7.8 years. Among participants with the APOE-e4 risk allele, higher intakes of total and saturated fat (SFA) were associated with a faster decline in global cognition. Among individuals with the APOE-e4 risk allele, a 5% increase in calories from SFA was associated with a 21% faster decline (β = -0.0197, P = 0.0038). In contrast, a higher intake of long-chain n-3 polyunsaturated fatty acids (LC-n3 PUFA) was associated with a slower rate of decline in global cognition among APOE-e4 carriers. Specifically, for every 1% energy increment from LC-n3 PUFA, the annual rate of global cognitive decline was slower by 0.024 standardized unit (SD 0.010, P = 0.023), about 30.4% slower annual cognitive decline. Higher SFA or other types of dietary fat were not associated with cognitive decline among APOE-e4 non-carriers.

Conclusions: Our study found a significant association between SFA and faster cognitive decline, LC-n3 PUFA and slower cognitive decline among those with the APOE-e4 allele. Our findings suggested that higher intake of SFA might contribute faster cognitive decline in combination with APOE-e4 whereas LC-n3 PUFA might compensate the adverse effects of APOE-e4. The interaction between intakes of different types of dietary fat and APOE-e4 on cognitive function warrants further research.

Keywords: APOE; Cognition; Cohort; Dietary fat; Long-chain fatty acid; Nutrition; Saturated fat.