(P29-022-24) Effect Modification by ApoE-Genotype of Estimated Effect of Macronutrients on Cognition, BMI, Blood Pressure, and LDL-Cholesterol: Observational Analyses in Older Adults

Objectives: Apolipoprotein E genotypes (ApoE) ε-3/4 and ε-4/4 constitute ≈30% of the Nordic population but ≈70% of diagnosed Alzheimer cases. We recently reported an interaction effect by ApoE where the estimated effect of a lower carbohydrate/fat-ratio (CFr) on global cognition was positive—distinctly for ε-3/4 and ε-4/4 (ApoE+, dichotomized against all others [ApoE–]) among participants of the Finnish geriatric intervention study to prevent cognitive impairment and disability (FINGER). Additionally, ε-4/4 had a remarkable negative slope between fiber intake and cognition. Objective of this study was to determine whether similar interaction effects extend to the outcomes BMI, systolic blood pressure, and LDL-cholesterol (LDL-C) concentrations in blood.

Methods: The FINGER sample was selected to be “at risk” for dementia, but participants were not diagnosed with cognitive impairment. These observational panel analyses used a sub-sample (n=676) with adequate biomarker data and absence of a diabetes diagnosis. Diet and the outcomes were measured at three consecutive years. The standardized effect of diet variables on the outcomes was estimated with mixed regression models stratified on ApoE [+/– (n=207/469), ε-4/4 (n=24)] and adjusted for confounders selected a priori.

Results: Characteristics of the sample were age 60–77 y, 46% females, and mean BMI: 27.7 kg/m². Interaction effects by ApoE+/– were shown for the estimated effect of CFr on BMI (p=0.0001), and blood pressure (p=0.006), but not LDL-C (p=0.26). Results per ApoE stratum (ApoE+/ApoE–) were CFr→BMI: β=0.001, p=0.85/β=–0.023, p=0.003; CFr→blood pressure: β=0.048, p=0.23/β=–0.052, p=0.01; CFr→LDL-C: β=–0.022, p=0.48/β=–0.044, p=0.01. For ε-4/4, the effect of fiber on LDL-C was β=–0.31, p< 0.0001, with a substantial interaction effect against all others combined (β=–0.23, p=0.002).

Conclusions: ApoE+ (ε-3/4 and ε-4/4) appear as promising targets for future clinical trials on carbohydrate restriction in the cognitive health field. A negative association between CFr and BMI, distinctly for ApoE–, may encourage further ApoE-stratification in metabolic research. For ε-4/4, lower fiber intake was associated with better cognition in combination with a hyper-response in LDL-C.

Funding Sources: Alzheimerfonden, af Jochnick Foundation