Interaction between APOE ε4 and dietary protein intake on cognitive decline: A longitudinal cohort study

Objective: To exam the association of cognitive decline with APOE e4 allele carriage and dietary protein intake and investigate whether there is a gene-diet (GxD) interaction of APOE e4 allele carriage and dietary protein intake on cognitive decline in a nationwide cohort of older adults. Methods: A cohort study of participants from Chinese Longitudinal Healthy Longevity Survey was conducted from 2008 to 2014. A total of 3029 participants (mean age of 77.0 years, SD = 9.0; 49.3% were women) was enrolled. We genotyped APOE e4 allele for each participant and calculated the diversity of dietary protein intake (DDPI) by summing up the frequency of intake of the 6 protein-rich foods (meats, fish, eggs, nuts, dairy products, and bean products). We assessed cognitive function using the MiniMental State Examination (MMSE). We used ordinal regression model to estimate the independent and joint effects of APOE e4 carrier and dietary protein intake on cognitive decline, adjusting for potential confounders of age, sex, education, socio-economic status, lifestyles, BMI, and cardiometabolic conditions. Results: There was significant association between carrying APOE e4 allele and faster cognitive decline (Odds ratio: 1.19, 95% CI = 1.00-1.42), independent of potential confounders. While the associations of DDPI and the intake of 6 protein-rich foods with cognitive decline did not reach any statistical significance. We observed significant interactions of APOE e4 with DDPI and fish intake, at multiple correctionadjusted Ps < 0.05. In those who were APOE e4 carriers rather than non-carriers, both high DDPI (OR = 0.54, 95% CI: 0.34-0.88) and daily fish intake (OR = 0.43, 95% CI: 0.22-0.78) were significantly associated with slower cognitive decline, respectively. We also found that frequent intake of fish benefits women more than men regarding the mitigating of cognitive decline among APOE e4 allele carriers (P for interaction = 0.016). Conclusions: The results of this study support the hypothesis that diversified protein food intake in addition to frequent fish intake may reduce the detrimental effect of APOE e4 on cognitive health. (c) 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Automated summary

The study found that individuals carrying the APOE e4 allele experienced faster cognitive decline, while high DDPI and daily fish intake were associated with slower cognitive decline. Additionally, frequent fish intake was more beneficial in mitigating cognitive decline among APOE e4 allele carriers, especially for women.