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APOE-genotype and Insulin Modulate Estimated Effect of Dietary Macronutrients on Cognitive Performance: Panel Analyses in Non-Diabetic Older Adults at Risk for Dementia
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden.
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden.
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden; Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London, London, United Kingdom; Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden.
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden; Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London, London, United Kingdom; Theme Inflammation and Aging, Medical Unit Aging, Karolinska University Hospital, Stockholm, Sweden; Stockholms Sjukhem, Research & Development Unit, Stockholm, Sweden.
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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 FoundationAvailable from: 2023-10-12 Created: 2023-10-12 Last updated: 2024-01-19Bibliographically approved

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