[Paper] Meat Consumption and Cognitive Health by APOE Genotype - 2026 [Epidemiology]
3d 10h ago by hackertalks.com/u/jet in carnivore@discuss.online from hackertalks.com
Question Is higher meat consumption associated with better cognitive health among individuals with APOE genotypes ε3/ε4 and ε4/ε4, and does this association differ from that observed in other genotypes?
Findings In this cohort study among 2157 older adults without dementia, higher total meat consumption was associated with slower cognitive decline and a reduced dementia risk among older adults with APOE ε3/ε4 and ε4/ε4 genotypes. Interactions by APOE genotype were observed for trajectories of global cognition and episodic memory.
Meaning These findings suggest that higher meat consumption than conventionally recommended may be associated with benefits in a genetically defined subgroup comprising approximately one-quarter of the global population.
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.
Full Paper - https://doi.org/10.1001/jamanetworkopen.2026.6489
Observational Epidemiology - Carbohydrate rich population (40+%), confounders, healthy user bias, Food frequency questionnaires, etc
Meat was protective for ape34/44 groups, and not harmful for other groups. All cause mortality also came down a bit.
Those authors propose that a hypercarnivorous period occurred a few million years ago, 10 which may correspond to APOE4 emergence, 2 followed by a return toward more plant-based diets in the last hundreds of thousands of years, coinciding with APOE3 emergence. Conflicting hypotheses suggest that APOE4 may provide more 5 or less11 adaptation to higher meat consumption.
Reviews of studies on meat consumption in association with cognitive health outcomes indicate that findings and methodologies are inconsistent.17-19 Some studies reported APOE interaction analyses, although outcomes were not statistically significant. 20,21 Our aim for this study was to estimate the effect of meat consumption on global cognition and dementia incidence among individuals with genotypes ε3/ε4 and ε4/ε4 (APOE34/44) compared with individuals with APOE22/ 23/24/33 (non-APOE34/44) genotypes in a population-based cohort of older adults. As stated prior to data access, 12 we hypothesized that higher meat consumption would be associated with distinct benefits among individuals with APOE34/44 genotypes
dietary assessments were conducted at baseline and at 3- and 6-year follow-ups.
Yup, a 15 year study with THREE Food Frequency questionnaires... and that is a lot for most epidemiology! Epidemiology is trash!
Dietary intake was assessed using validated, semiquantitative, 98-item food-frequency questionnaires capturing diet over the previous year
In the last twelve months how many servings of potatoes did you eat on average per week? Trash, TRASH.
the model included age, sex, education, APOE status, living arrangements, lifelong occupation type, physical activity level, current smoking status, alcohol intake, total energy intake, and Alternative Healthy Eating Index (AHEI) score, 29 excluding meat items, as a marker for adherence to dietary guidelines.
The guidelines already try to exclude meat, so you can't be "healthy" if you eat meat, so the model has to counter control for the healthy user bias... notice they don't look at carbs as a confounder.
Lets not forget survival bias, to get to be old enough to participate in this study you have to survive... people eating lots of carbs have trouble surviving this long, as you can see by the low hba1c scores in the quintiles compared to the general population... people following the healthy eating guidelines who are not adapted to high carb eating will die out before they make it into the study..... thats a hell of a confounder.
Indirect evidence of a similar APOE interaction was implied by reports that the low-meat EAT-Lancet 40 and Planetary Healthy diets41 were favorably associated with cognitive health outcomes only among non–APOE4 carriers. Notably, the 2025 EAT-Lancet 2.0 42 cites the NHS and UK Biobank studies discussed previously to support the statement that “red meat has been positively associated with…unhealthy ageing,” a conclusion that is contradicted by our interpretation
I heavily distrust the lancet people, they have demonstrated heavy bias through many of their publications on plants and meat, to the point i assume they are intentional and i would need to see third party interventional trials to even consider a lancet data point as credible.
In this cohort study, we found that the APOE34/44 group exhibited the anticipated excess risk of cognitive decline and dementia progression compared with participants with other genotypes when consuming meat at levels consistent with current dietary guideline targets. However, this disadvantageous association was absent at higher consumption levels, equivalent to more than twice the target.33 Viewed alongside reinterpreted evidence from NHS 37 and UK Biobank21 focusing on unprocessed meat, these findings point to a consistent gene-diet interaction, with important implications for public health. Results reinforce the urgency of investing in precision nutrition research with a focus on APOE, which could ultimately inform future policy development
Precision nutrition is a cop out allowing researchers to kick the can and not address the white elephant in the room, focus on carbohydrates! It's not that the modern diet is antithetical to health, its that all the sick people require precision nutrition prescription (to cut out carbs and eat more meat)......