APOE‐e4 Status Moderates Associations between Executive Function and Air Pollution Exposure in Older Men
Bibliographic record
Abstract
Abstract Background Air pollution, which includes exposure to tiny particulate matter (PM2.5) and Nitrogen Dioxide (NO2) is a notable public health hazard. Exposure has adverse effects on multiple health outcomes as well as with increased risk of developing cognitive impairment and Alzheimer’s disease and related dementias. Although the primary cognitive focus in Alzheimer’s disease is memory, there is growing recognition of the importance of early executive function (EF) deficits as a risk indicator. In addition, there is some evidence of genetic susceptibility to pollution‐related cognitive decline. Few studies have strong measures of air pollution, EF, as well as APOE genotyping. We recently showed that APOE genotype was associated with significant decline in EF from middle to early old age among individuals who were cognitively unimpaired at baseline (Gustavson et al, 2022). Here we tested the hypothesis that the impact of air pollution on executive functions would be greater in APOE‐ε4+ carriers compared with APOE‐ε4‐ individuals. Method We examined associations between exposure in midlife and EF from midlife to early old age in ∼800 men from the Vietnam Era Twin Study of Aging. Measures included average PM2.5 and NO2 exposure in the three years prior to the time 1 (mean age 56; range 51‐61) assessment, and an executive function factor score at time 1 and time 2 (mean age 68; range 65‐72). GEE analyses adjusted for multiple health and lifestyle covariates, as well as the random effect of family. Result Cognitive performance declined over time from age 56 to age 68 (F = 439.38, p<0.0001). There were no main effects of air pollution on EF. Overall APOE‐ε4+ carriers had higher EF performance than non‐carriers (F = 5.43, p = 0.02). In addition, we found a significant PM2.5‐by‐APOE genotype interaction (F = 8.80, p = 0.003). Increased exposure to PM2.5 in midlife was related to lower executive function in APOE‐ε4 carriers, but not non‐carriers. The interaction with NO2 did not reach significance (F = 2.83, p = 0.09). Conclusion These results indicate that midlife PM2.5 exposure in men is associated with poorer frontal‐executive function, and APOEε4 carriers are more susceptible to the deleterious effects of PM2.5.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".