APOE ɛ4 Gene Dose and Sex Effects on Alzheimer’s Disease MRI Biomarkers in Older Adults with Mild Cognitive Impairment
Bibliographic record
Abstract
BACKGROUND: APOEɛ4 and sex have been linked to increased risk for conversion to Alzheimer's disease (AD). However, the relationship between APOEɛ4 gene dose, sex, and AD biomarkers remains understudied. OBJECTIVE: To investigate the effect of APOEɛ4 dose on AD biomarkers in a sample of older adults with mild cognitive impairment (MCI), and to examine whether APOEɛ4 dose modifies AD risk differently in MCI women and men. METHODS: We examined cross-sectional AD biomarkers for participants with MCI (n = 930, 55-96 years old) from three large aging cohorts. Region of interest MRI volumes, global cognition, and episodic memory were analyzed by number of APOEɛ4 alleles and stratified by sex. RESULTS: Across all participants, number of APOEɛ4 alleles was associated with smaller hippocampal and amygdala volumes and poorer cognition. When stratified by sex, women showed an APOEɛ4 dose effect for bilateral hippocampal and left amygdala volumes and cognition. In contrast, men showed an APOEɛ4 dose effect for hippocampal volumes with a trend in amygdala, but cognition did not differ between men with 1 and 2 APOEɛ4 alleles. Women with 2 APOEɛ4 alleles had poorer memory between 65-69 and poorer global cognition between 70-74 compared to men with 2 APOEɛ4 alleles. CONCLUSION: APOEɛ4 confers a dose effect on AD biomarkers in patients with MCI, and the number of APOEɛ4 alleles has a greater detrimental impact in women than men, which may be specific to a critical time window.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".