Higher total meat consumption was associated with more favorable cognitive trajectories among older patients with apolipoprotein E epsilon 3/epsilon 4 and epsilon 4/epsilon 4 genotypes, according to a cohort study published in JAMA Network Open.
In contrast, no such association was observed among patients with other genotypes, and the study did not find statistically significant interaction by genotype for dementia risk.
Researchers analyzed data from 2,157 patients aged 60 years or older without dementia at baseline in the Swedish National Study on Aging and Care–Kungsholmen, with up to 15 years of follow-up. Cognitive trajectory analyses were conducted in a subset of 1,680 patients with longitudinal cognitive data.
Cognitive Trajectories Varied by Genotype
Among patients with epsilon 3/epsilon 4 or epsilon 4/epsilon 4 genotypes, higher total meat intake was associated with slower cognitive decline over time. Patients in the highest intake group showed better global cognition and episodic memory trajectories compared with those in the lowest intake group.
By contrast, no meaningful association between meat intake and cognitive change was observed among patients with other genotypes.
Interaction analyses indicated that genotype modified associations for global cognition and episodic memory, suggesting a potential gene–diet relationship.
Dementia Risk Findings Less Definitive
Patterns for dementia risk were directionally similar but less conclusive. Among patients with epsilon 3/epsilon 4 or epsilon 4/epsilon 4 genotypes, higher meat intake was associated with lower dementia risk, whereas no association was observed among other genotypes.
However, the interaction between genotype and meat intake for dementia risk was not statistically significant, indicating that differences between genotype groups should be interpreted cautiously.
Processed Meat Ratio Linked to Worse Outcomes
A higher ratio of processed to total meat intake was associated with increased dementia risk and less favorable cognitive trajectories overall. These associations were not significantly modified by genotype.
When examining meat subtypes, researchers found no substantial differences between unprocessed red meat and poultry. Higher intake of unprocessed red meat was associated with lower dementia risk across genotype groups.
Subgroup and Sensitivity Analyses
Associations between higher meat intake and favorable cognitive outcomes were more evident among female patients, those aged 72 years or younger, and those with higher hemoglobin A1C levels or higher Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) scores. No statistically significant interaction by sex was observed.
Sensitivity analyses, including within-patient and cross-sectional approaches, showed consistent results. Excluding patients with possible cognitive impairment did not materially change findings.
In post hoc analyses, higher unprocessed meat intake was associated with lower all-cause mortality among patients with epsilon 3/epsilon 4 or epsilon 4/epsilon 4 genotypes, with opposite trends observed in other genotypes.
Study Design and Limitations
The study used repeated dietary and cognitive assessments and statistical approaches designed to approximate causal inference. Analyses adjusted for demographic factors, lifestyle variables, comorbidities, total energy intake, and dietary quality.
Limitations included potential residual confounding, reliance on self-reported dietary data, and limited generalizability due to the predominantly Northern European population. Survival bias could not be excluded.
“The expected cognitive disadvantage among individuals with APOE34/44 genotypes was not observed at high meat consumption, suggesting clinical and public health relevance,” wrote lead researcher Jakob Norgren, PhD, of Karolinska Institutet in Sweden, and colleagues.
Disclosures
Maria Eriksdotter, MD, PhD, reported receiving consulting fees from Bioarctic AB, Eli Lilly, Eisai/Bioarctic, and Novo Nordisk outside the submitted work. No other disclosures were reported.
Source: JAMA Network Open
