Summary:
APOE, a gene that moves cholesterol and fat around the body, is a major genetic modifier of Alzheimer disease, with one of its variants, APOE4, having the highest risk. APOE4 considered the ancestral form, while APOE3 and APOE2 emerged later in human evolution. Because dietary patterns shifted over evolutionary time, from periods of high meat intake to more plant‑based diets, researchers have proposed that different APOE genotypes may reflect adaptations to these changing food environments. Some hypotheses suggest APOE4 may be better suited to higher meat consumption. Evidence linking meat intake to cognitive outcomes has been inconsistent, and few studies have examined whether different APOE genotypes modify this relationship. This study is a population‑based cohort analysis using 15 years of follow‑up data from older adults in Sweden, tested whether meat consumption was associated with cognitive impairment and dementia risk differently for individuals with varying APOE genotypes. The study included 2,157 adults aged 60 or older without dementia at baseline. Meat intake was measured using food‑frequency questionnaires, and cognitive change and dementia incidence were assessed over time. Among participants with certain genotypes, higher meat consumption was associated with better cognitive outcomes and lower dementia risk. No such associations were observed in individuals with other APOE genotypes. A higher proportion of processed meat was linked to increased dementia risk regardless of genotype. These findings suggest that higher meat intake may mitigate cognitive decline and dementia risk specifically among individuals with an identified genotype. At high levels of meat consumption, the expected cognitive disadvantage associated with APOE4 was not evident.
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Abstract:
Importance: The apolipoprotein E (APOE) ε4 allele increases Alzheimer disease risk. Understanding genotype-specific dietary needs could inform more personalized prevention strategies. Objective: To test the hypothesis that higher meat consumption may be associated with cognitive health benefits in individuals with APOE genotypes ε3/ε4 and ε4/ε4 (APOE34/44) and to examine whether this association differs from that in other genotypes. Design, Setting, and Participants This population-based cohort study used panel data analyses conducted in January 2025 to January 2026 over 15 years of follow-up in the Swedish National Study on Aging and Care–Kungsholmen (SNAC-K), using strategies aligned with causal inference principles. Recruitment was done in 2001 to 2004 among adults without dementia aged 60 years or older. Exposures: The primary exposure was total meat consumption in grams per total kilocalories assessed via validated food frequency questionnaires. The secondary exposure was the ratio of processed to total meat. Main Outcomes and Measures Global cognitive trajectory, measured as change in z score per 10 years, was analyzed by linear regression. Incident dementia was analyzed using Fine and Gray subdistribution hazard ratios (sHRs), treating nondementia death as a competing risk. Results: Among 2157 older adults without dementia (mean [SD] age 71.2 [9.2] years; 1337 female [62.0%]), 1680 participants had longitudinal cognition data and 569 participants (26.4%) had APOE34/44 genotypes. During follow-up, 296 participants developed dementia and 690 died without dementia. Among participants with APOE34/44 genotypes, higher total meat consumption (top vs bottom quintile) was associated with better cognitive trajectories (β = 0.32; 95% CI, 0.07 to 0.56; P = .01) and reduced dementia risk (sHR, 0.45; 95% CI, 0.21 to 0.95; P = .04). No associations were found in participants with APOE22/23/24/33 genotypes (cognitive trajectory: β = –0.11; 95% CI, –0.27 to 0.06; P = .20; dementia: sHR, 0.95; 95% CI, 0.57 to 1.61; P = .86). P values for APOE interaction were .004 for cognition and .10 for dementia. In the top quintile of meat consumption, dementia risk and cognitive decline were similar between APOE strata. A higher ratio of processed to total meat was unfavorably associated with dementia (sHR, 1.14; 95% CI, 1.01 to 1.29; P = .04), showing no APOE interaction and no substantial difference between unprocessed red meat and poultry. Post hoc analyses suggested concordant APOE interaction for all-cause mortality (unprocessed meat exposure, APOE34/44: HR, 0.85; 95% CI, 0.73 to 0.99; P = 0.04; P for interaction = .03). Conclusions and Relevance: In this study, higher meat consumption was associated with better cognitive trajectories and lower dementia risk among individuals with APOE34/44 genotypes. The expected cognitive disadvantage among individuals with APOE34/44 genotypes was not observed at high meat consumption, suggesting clinical and public health relevance.
Article Publication Date: 19/03/2026
DOI: 10.1001/jamanetworkopen.2026.6489
