APOE-genotype and Insulin Modulate Estimated Effect of Dietary Macronutrients on Cognitive Performance: Panel Analyses in Non-Diabetic Older Adults at Risk for DementiaShow others and affiliations
2023 (English)In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 153, no 12, p. 3506-3520Article in journal (Refereed) Published
Sustainable development
00. Sustainable Development, 3. Good health and well-being
Abstract [en]
BACKGROUND: The APOE-gene (ε-2/3/4, combined as six different genotypes: ε-22/23/24/33/34/44) and insulin status modulate dementia risk and play a role in the metabolism of macronutrients.
OBJECTIVE: Our aim was to examine APOE-genotype and fasting insulin as effect-modifiers of the slopes between dietary macronutrients and cognitive performance among older adults at risk for dementia.
METHOD: Panel analyses-with diet and cognition measured at baseline and follow-up at year 1 and 2-were performed in a sub-sample from the FINGER trial (n=676, 60-77 years, 46% females, all non-diabetics). The associations between macronutrients (3-day food records, z-scores) and global cognition (modified Neuropsychological Test Battery, z-score) were analyzed in mixed regression models adjusted for confounders selected a priori. After a gradient was implied by the point estimates in categorical APOE-analyses, we investigated a continuous APOE variable [APOE-gradient, coded -1 (for ε-23), -0.5 (ε-24), 0 (ε-33), 1 (ε-34), 2 (ε-44)] as an effect-modifier.
RESULTS: At increasing levels of the APOE-gradient a relatively more favorable slope between diet and cognition was observed for a lower carbohydrate/fat-ratio (β=-0.040, 95% CI -0.074, -0.006, P=0.020 for interaction diet x APOE-gradient), and higher protein (β=0.075, CI 0.042, 0.109, P=9.4x10-6). Insulin concentration (log-linear) modulated the association between CFr and cognition by a quadratic interaction (β=-0.016, P=0.039). Coherent findings for exploratory predictors (fiber, fat-subtypes, composite score, metabolic biomarkers) were compatible with published hypotheses of differential dietary adaptation by APOE, with cognition among ε-33 being relatively independent of dietary parameters-implying "metabolic flexibility". Antagonistic slopes to cognition for ε-23 (positive) versus ε-34 and ε-44 (negative) were found for a Higher-carbohydrates-fiber-Lower-fat-protein composite score, even as within-subjects effects.
CONCLUSIONS: APOE-based precision nutrition appears conceptually promising but replications in wider samples are warranted, as well as support from trials. Both relative hyper- and hypo-insulinemia might modulate the effect of diet on cognition.
Place, publisher, year, edition, pages
Elsevier, 2023. Vol. 153, no 12, p. 3506-3520
Keywords [en]
Alzheimer, apolipoprotein E, gene-nutrient interaction, insulin resistance, target trial
National Category
Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:hj:diva-62659DOI: 10.1016/j.tjnut.2023.09.016ISI: 001135161400001PubMedID: 37778510Scopus ID: 2-s2.0-85176272918Local ID: HOA;;909127OAI: oai:DiVA.org:hj-62659DiVA, id: diva2:1804399
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Research CouncilKnut and Alice Wallenberg FoundationAlzheimerfondenThe Swedish Brain Foundation2023-10-122023-10-122024-01-19Bibliographically approved