Nutritional Status and Cognition in Older Adults: Modification by Apolipoprotein E ε4

Background: Malnutrition is a modifiable risk factor for late-life cognitive decline, but whether its cognitive correlates vary by genetic risk is unclear. We examined whether the apolipoprotein E ε4 allele (APOE4) modifies associations of the Mini-Nutritional Assessment (MNA) and its subscales with global cognition. Methods: In this cross-sectional analysis of 196 non-demented older Korean adults from the General Lifestyle and Alzheimer's Disease (GLAD) cohort, multiple linear regression tested associations of MNA total (MNA-T), screening (MNA-S), and assessment (MNA-A) scores with the CERAD total score (TS), including MNA × APOE4 interactions. Exploratory analyses examined one representative item per a priori nutritional domain. Results: After adjustment, MNA-T (p = 0.006) and MNA-A (p = 0.003), but not MNA-S (p = 0.065), were associated with TS. APOE4 carrier status modified these associations (interaction p = 0.005 and 0.007, respectively); associations were evident in non-carriers but not in carriers, an underpowered subgroup (n = 40). Among the domain-representative items, only self-rated health survived Bonferroni correction (p = 0.006); protein intake (p = 0.025) and calf circumference (p = 0.043) showed nominal associations only. Conclusions: Better nutritional status was associated with better global cognition, predominantly in APOE4 non-carriers. These hypothesis-generating findings require confirmation in larger longitudinal and interventional studies.