APOE-Genotype and Insulin Modulate Estimated Effect of Dietary Macronutrients on Cognitive Performance: Panel Analyses in Nondiabetic Older Adults at Risk of Dementia
The apolipoprotein E gene (APOE ε-2/3/4, combined as 6 different genotypes: ε-22/23/24/33/34/44) and insulin status modulate dementia risk and play a role in the metabolism of macronutrients. We aimed to examine APOE-genotype and fasting insulin as effect modifiers of the slopes between dietary macr...
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Published in | The Journal of nutrition Vol. 153; no. 12; pp. 3506 - 3520 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Institute of Nutrition
01.12.2023
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Subjects | |
Online Access | Get full text |
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Summary: | The apolipoprotein E gene (APOE ε-2/3/4, combined as 6 different genotypes: ε-22/23/24/33/34/44) and insulin status modulate dementia risk and play a role in the metabolism of macronutrients.
We aimed to examine APOE-genotype and fasting insulin as effect modifiers of the slopes between dietary macronutrients and cognitive performance among older adults at risk of dementia.
Panel analyses-with diet and cognition measured at baseline and follow-up at years 1 and 2-were performed in a sub-sample from the FINGER (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) trial (n = 676, 60-77 y, 46% females, all nondiabetics). The associations between macronutrients (3-d 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.
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% confidence interval (CI): -0.074, -0.006; P = 0.020 for interaction diet × APOE-gradient), and higher protein (β = 0.075, 95% CI: 0.042, 0.109; P = 9.4 × 10
). Insulin concentration (log-linear) modulated the association between the carbohydrate/fat ratio 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) compared with ε-34 and ε-44 (negative) were found for a Higher-carbohydrates-fiber-Lower-fat-protein composite score, even as within-subjects effects.
APOE-based precision nutrition appears conceptually promising, but replications in wider samples are warranted, as well as support from trials. Both relative hyper- and hypoinsulinemia might modulate the effect of diet on cognition. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3166 1541-6100 1541-6100 |
DOI: | 10.1016/j.tjnut.2023.09.016 |