Older people with gene variants associated with higher Alzheimer’s risk didn’t show the expected cognitive decline if they ate relatively high amounts of meat. Instead, those with these genes who consumed the most meat had slower cognitive decline and lower dementia risk, challenging conventional dietary advice.
This key finding from Karolinska Institutet scientists, published in JAMA Network Open, suggest that dietary advice could eventually be tailored more precisely based on a person’s genetic profile.
The APOE gene plays a major role in determining Alzheimer’s risk. In Sweden, about 30% of people carry the APOE 3/4 or APOE 4/4 gene combinations. Among those diagnosed with Alzheimer’s disease, nearly 70% have one of these variants.
Last year, the Swedish Food Agency reviewed existing research on diet and dementia and called for more studies to better understand how meat consumption might influence dementia risk.
Why they studied meat intake
“This study – testing the hypothesis that people with APOE 3/4 and 4/4 would have a reduced risk of cognitive decline and dementia with higher meat intake – was based on the fact that APOE4 is the evolutionarily oldest variant of the APOE gene and may have arisen during a period when our evolutionary ancestors ate a more animal-based diet,” said first author Jakob Norgren, researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.
Long-term study of diet and brain health
The research followed more than 2 100 adults participating in the Swedish National Study on Ageing and Care, Kungsholmen (SNAC-K). All participants were at least 60 and free of dementia at the beginning of the study. They were tracked for up to 15 years.
Researchers analysed self-reported dietary habits alongside measures of cognitive health, while accounting for factors like age, sex, education, and lifestyle.
Meat intake and dementia risk
Among those who ate less meat, participants with APOE 3/4 and 4/4 had more than twice the risk of developing dementia than individuals without these gene variants.
However, this elevated risk was not observed in the group that consumed the most meat. In this highest-intake group, median consumption was about 870 grams of meat per week, adjusted to a daily energy intake of 2 000 calories.
“Those who ate more meat overall had significantly slower cognitive decline and a lower risk of dementia, but only if they had the APOE 3/4 or 4/4 gene variants,” said Norgren.
“There is a lack of dietary research into brain health, and our findings suggest that conventional dietary advice may be unfavourable to a genetically defined subgroup of the population. For those who are aware that they belong to this genetic risk group, the findings offer hope: the risk may be modifiable through lifestyle changes.”
Processed vs unprocessed meat matters
The type of meat also appeared to make a difference. “A lower proportion of processed meat in total meat consumption was associated with a lower risk of dementia regardless of APOE genotype,” said Sara Garcia-Ptacek, assistant Professor at the same department, who with senior lecturer Erika J Laukka, is the study’s last author.
Potential benefits beyond brain health
The researchers also found broader health effects. In a follow-up analysis, people with APOE 3/4 and 4/4 who consumed more unprocessed meat had a significantly lower risk of death from any cause.
Limitations, need for clinical trials
Because the study is observational, it cannot prove cause and effect. More rigorous intervention studies are needed to confirm whether dietary changes directly influence dementia risk.
“Clinical trials are now needed to develop dietary recommendations tailored to APOE genotype,” noted Norgren.
“Since the prevalence of APOE4 is about twice as high in the Nordic countries as in the Mediterranean countries, we are particularly well suited to conduct research on tailored dietary recommendations for this risk group.”
Facts about the APOE gene
Apolipoprotein E plays a key role in transporting cholesterol and fats in both the brain and bloodstream. The APOE gene has three main forms: epsilon 2, 3, and 4. These variants influence the likelihood of developing Alzheimer’s disease and cardiovascular disease.
Each person inherits two copies of the gene, one from each parent, resulting in six possible combinations (genotypes): 2/2, 2/3, 2/4, 3/3, 3/4, and 4/4.
Compared with the most common genotype 3/3, having one copy of the 4 variant increases Alzheimer’s risk by about three to four times, while having two copies raises the risk by about 10 to 15 times. The 2 variant is linked to a lower risk. However, these risk levels can vary across different ethnic groups. Source: Belloy et al., JAMA Neurology, 2023
Study details
Meat Consumption and Cognitive Health by APOE Genotype
Jakob Norgren, Adrián Carballo-Casla, Giulia Grande et al.
Published in JAMA Network Open on 2026;
Abstract
Importance
The apolipoprotein E (APOE) ε4 allele increases Alzheimer disease risk. Understanding genotype-specific dietary needs could inform more personalised 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 Ageing 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 analysed by linear regression. Incident dementia was analysed using Fine and Gray subdistribution hazard ratios (sHRs), treating non-dementia death as a competing risk.
Results
Among 2 157 older adults without dementia (mean [SD] age 71.2 [9.2] years; 1337 female [62.0%]), 1 680 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 unfavourably 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).
JAMA Network Open article – Meat Consumption and Cognitive Health by APOE Genotype (Open access)
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