APOE Genotype Modifies the Association between Midlife Adherence to the Planetary Healthy Diet and Cognitive Function in Later Life among Chinese Adults in Singapore

Background: It remains unclear if adherence to the planetary healthy diet (PHD), designed to improve human and environmental health, is associated with better cognitive function in aging, and if this association differs by apolipoprotein E (APOE) genotype. Objectives: We aimed to examine the association between the PHD pattern and risk of poor cognitive function, and to further assess whether the APOE e4 allele could modify this association. Methods: The study included 16,736 participants from the Singapore Chinese Health Study. The PHD score was calculated using data from a validated 165 -item food frequency questionnaire at baseline (1993-1998), with higher scores indicating greater adherence to the PHD. Cognitive function was assessed by the Singapore -modified Mini -Mental State Examination at follow-up 3 visits (2014-2016). A subset of 9313 participants had APOE genotype data. Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders. Results: We identified 2397 (14.3%) cases of poor cognitive function. In the total population, OR (95% CI) of poor cognitive function for each one -SD increment in the PHD score was 0.89 (0.85, 0.93). Carriers of APOE e4 allele had increased risk of poor cognitive function (OR: 1.36, 95% CI: 1.15, 1.61). There was a significant interaction between the PHD score and the APOE e4 allele (P -interaction 1/4 0.042). Each one -SD increment in the PHD score was significantly associated with lower risk of poor cognitive function (OR: 0.89; 95% CI: 0.83, 0.96) in non -carriers of APOE e4 allele, but not in APOE e4 allele carriers (OR: 1.04, 95% CI: 0.89, 1.23). Conclusions: Midlife adherence to the PHD was associated with reduced risk of poor cognitive function in later life. However, this was not observed in carriers of APOE e4 allele who had higher risk of poor cognitive function.