APOE-ε4 moderates the association between diet quality and executive function in middle-aged women at increased risk for Alzheimer’s disease

We examined whether diet quality is associated with executive function (EF) in middle-aged women with a family history of Alzheimer’s disease (AD) and whether this is moderated by a genetic AD risk factor, APOE-ε4 allele carriage. Data from 102 low-physically active women ( Age Mean = 56.9 ± 5.8 years) were analyzed cross-sectionally. Diet quality was quantified via the Healthy Eating Index-2020 (HEI-2020). Overall EF and sub-domains (working memory [WM], exogenous inhibitory control [ICex], endogenous inhibitory control [ICen], and cognitive flexibility) were measured using neurocognitive assessments. APOE-ε4 carriage was determined from saliva. Moderated regression models tested HEI-2020*APOE-ε4 interactions; significant ( p < .05) and near-significant ( p < .10) interactions were followed by simple slope analyses. Main effects of HEI-2020 predicted overall EF ( p = .033) and WM ( p = .003). Interaction effects of HEI-2020*APOE-ε4 for EF and WM ( p’s = .056–.038) were such that diet quality was positively associated with overall EF ( p = .003) and WM ( p = .005) in noncarriers only. Main effects of select HEI-2020 sub-scores were observed for overall EF and sub-domains ( p’s = .001–.047). Interaction effects of total vegetables*APOE-ε4 on overall EF and ICex, saturated fatty acids*APOE-ε4 on overall EF and WM, and added sugars*APOE-ε4 on ICen ( p’s = .007–.074) were such that sub-scores were positively associated with cognition in noncarriers only ( p’s < .05). Diet quality and select sub-scores were positively associated with EF in middle-aged women without APOE-ε4 only. Future work should explore if APOE-ε4 carriers require a threshold of diet quality to yield cognitive benefits.