Does <i>APOE4</i> genotype moderate the effects of multidomain exercise interventions in older individuals living with mild cognitive impairment?
Bibliographic record
Abstract
BACKGROUND: Mild Cognitive Impairment (MCI) may be associated with the presence of the apolipoprotein E4 allele (APOE4), a genetic factor linked to accelerated cognitive decline. The SYNERGIC trial demonstrated that physical exercise (PE) involving aerobic and resistance training improves global cognition in individuals with MCI, with significantly enhanced benefits of cognitive training but not vitamin D. The role of APOE4 status in responsiveness to these interventions remains unclear. METHOD: Of 175 participants in the SYNERGIC trial, 80 underwent APOE4 genotyping. This study analyzed 67 participants (mean age: 73.8 years; 43.2% women) who completed a 6-month multidomain intervention across four arms: (1) PE + Cognitive training (Neuropeak®) + Vitamin D; (2) PE + Cognitive training; (3) PE + Vitamin D; and (4) PE alone. Changes in global cognition (ADAS-Cog-13) were compared between APOE4-positive and APOE4-negative individuals using ANOVA. RESULT: APOE4-positive participants showed attenuated global cognitive improvements from multidomain interventions compared to APOE4-negative participants (mean difference = -2.08, 95% CI: -4.18 to 0.11; p = 0.052; d = -0.56). A significant group effect (p = 0.03) revealed that the PE + Vitamin D arm worsened global cognition over time compared to all other arms, with significant decline relative to the arm receiving all three interventions (p = 0.02). Sensitivity analysis excluding arms with vitamin D confirmed the attenuated effect of APOE4-positive status on global cognition (mean difference = -2.99, 95% CI: -6.10 to 0.11; p = 0.05; d = -0.78). CONCLUSION: Individuals with MCI and APOE4-positive status exhibit reduced responsiveness to multidomain interventions for global cognition, likely due to underlying genetic neurodegeneration.
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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 | 0.004 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".