Walking to Protect Against Cognitive Decline: The Role of APOE Genotype, Sex, and Race
Bibliographic record
Abstract
BACKGROUND: The apolipoprotein E (APOE) ε4 allele is a well-established genetic risk factor for cognitive decline and late-onset Alzheimer's disease with stronger effects in females, while the ε2 allele may offer protective effects. Physical activity is known to mitigate cognitive decline; whether the degree of benefit differs by APOE genotype, sex, and race remains unknown. METHODS: Analyses utilized data from 2,984 participants in the Health, Aging, and Body Composition cohort, comprising community-dwelling black and white older adults followed for 10 years. Cognitive performance was assessed longitudinally using the Digit Symbol Substitution Test (DSST) for executive functions/processing speed and the Modified Mini-Mental State Examination (3MS) for global cognition. APOE genotypes were categorized into ε2, ε3, and ε4 groups. Physical activity was quantified using self-reported annual walking time. Linear models and latent growth curve modeling examined the interactions between APOE genotype, sex, race, and walking on cognitive trajectories with adjustments for study location, health score, age, education, and body mass index. RESULTS: APOE ε4 carriers demonstrated steeper declines in both DSST and 3MS scores compared to ε3 carriers, irrespective of sex and race (βs>-0.07, all p <0.034). There was some evidence that APOE ε2 was protective against cognitive decline, however associations were inconsistent across sex and race. Walking showed the strongest protective effect in ε4 carriers, slowing the decline in DSST among black females (β=0.39, p = 0.039), white females (β=0.60, p = 0.008), and white males (β=0.45, p = 0.009) (Figure 1). For 3MS, walking was associated with slower decline across ε4 carriers with slightly greater associations in black individuals (βs>1.11, p <0.001) compared to white (βs>0.67, p <0.031) (Figure 1). Walking was not associated with cognition decline in ε2 or ε3 carriers (Figure 1). CONCLUSIONS: APOE ε4 carriers displayed an elevated risk of cognitive decline; greater physical activity was significantly protective in this at-risk group. Greater walking was associated with better executive function/processing speed in white ε4 carriers, and better global cognition in black ε4 carrier. These findings underscore the importance of tailoring public messaging about physical activity strategies to at-risk vulnerable populations and highlight the intersection of genetic, sex, demographic, and lifestyle factors in cognitive aging research.
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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 | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".