Examining the interaction of sex and APOE 4 status in predicting hallucinations relative to delusions in AD
Bibliographic record
Abstract
BACKGROUND: The APOE4 allele is a significant genetic risk factor for Alzheimer's disease (AD). Prior work from our group suggests that among neuropathologically verified AD patients, homozygous APOE4 status increases psychosis risk in females compared to heterozygotes, non-carriers, and males but only in the presence of Lewy Body (LB) pathology. This study examines the effects of APOE4 carrier status (homozygous, heterozygous, or non-carrier) and sex on the visual hallucinations relative to auditory hallucinations and delusions in AD. We hypothesize that female-specific findings will be greater in visual hallucinations compared to auditory hallucinations and delusions given they are a proxy of LB pathology. METHOD: Patient data was extracted from the NACC database. The sample was limited to patients with an etiologic diagnosis of AD. Psychosis was defined based on Neuropsychiatric Inventory subscores for delusions and hallucinations. We analyzed data separately for female APOE4 homozygotes, heterozygotes and non-carriers as well as male APOE4 homozygotes, heterozygotes and non-carriers using a binary logistic regression. Covariates, including age, education, Montreal Cognitive Assessment (MoCA) scores, and Mini-Mental State Examination (MMSE) scores, were controlled for in all analyses. RESULT: When pooling males and females together, APOE4 homozygotes had a significantly greater likelihood of auditory hallucinations compared to heterozygotes and delusions compared to non-carriers (p < .05). When comparing female APOE4 homozygotes relative to female heterozygotes and non-carriers, homozygous individuals displayed a greater likelihood of hallucinations compared to non-carriers (p < 0.05). Among males there were significant differences in hallucinations overall, visual and auditory among homozygotes relative to heterozygotes and no differences with non-carriers (p < .05). CONCLUSION: Findings suggest that APOE4 homozygosity increases psychosis risk among males relative to heterozygotes and females relative to non-carriers, with effects being limited to hallucinations. Pooled analyses in both sexes showed effects of APOE4 mainly in delusions and auditory hallucinations. This data suggests the sex effects of APOE4 may be stronger for hallucinations relative to delusions though further studies in larger samples are needed to corroborate this finding. It should also be noted that these analyses did not adjust for LB pathology.
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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 | 0.002 | 0.009 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".