APOE-Genotype and Insulin Modulate Estimated Effect of Dietary Macronutrients on Cognitive Performance : Panel Analyses in Nondiabetic Older Adults at Risk of Dementia

• Background: The apolipoprotein E gene (APOE e-2/3/4, combined as 6 different genotypes: e-22/23/24/33/34/44) and insulin status modulate dementia risk and play a role in the metabolism of macronutrients.Objectives: 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. Methods: 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% fe -males, all nondiabetics). The associations between macronutrients (3-d food records, z-scores) and global cognition (modified Neuropsy-chological 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 e-23), -0.5 (e-24), 0 (e-33), 1 (e-34), 2 (e-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 [p = -0.040, 95% confidence interval (CI): -0.074, -0.006; P = 0.020 for interaction diet x APOE-gradient), and higher protein (p = 0.075, 95% CI: 0.042, 0.109; P = 9.4 x 10-6). Insulin concentration (log-linear) modulated the association between the car-bohydrate/fat ratio and cognition by a quadratic interaction (p = -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 e-33 being relatively independent of dietary parameters-implying metabolic flexibility. Antagonistic slopes to cognition for e-23 (positive) compared with e-34 and e-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 hypoinsulinemia might modulate the effect of diet on cognition.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Näringslära (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Nutrition and Dietetics (hsv//eng)

Nyckelord

gene-nutrient interaction

apolipoprotein E

insulin resistance

Alzheimer's disease

lifestyle medicine

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