APOE ε4-related differences in brain structure, function, and connectivity at midlife: A scoping review
Bibliographic record
Abstract
BACKGROUND: The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for late-onset Alzheimer's disease (AD), yet there is little consensus about how and when the allele exerts its influence on the brain. METHODS: In this scoping review, we synthesized research examining APOE ε4-related differences on MRI-derived measures of brain structure, function, and connectivity in cognitively unimpaired, middle-aged adults (aged 40-65 years). Four online databases (Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, Scopus) were searched on July 11, 2024, and forward/backward reference searching was conducted on identified studies. We extracted data on sample characteristics, methods, and key APOE ε4-related results. RESULTS: Our pre-registered search strategy identified 30 relevant studies. Overall, we found little evidence of robust, consistent differences between APOE ε4 carriers and non-carriers at midlife, especially in relation to brain structure. However, among the studies identified, small samples were common, and limited consideration was afforded to factors such as sex and ethnocultural diversity. CONCLUSION: Overall, the existing literature indicates that APOE ε4 exerts little, if any, influence on brain structure at midlife, while differences in brain function and connectivity remain poorly characterized.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.011 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".