Determining whether sex and zygosity modulates the association between ApoE4 and psychosis in a neuropathologically‐confirmed Alzheimer’s disease cohort
Bibliographic record
Abstract
Abstract Background Individuals with the APOE ε4 allele (ApoE4) have an increased risk of developing Alzheimer’s disease (AD) compared to individuals with the more common ε2 or ε3 alleles. Previous work by our group found that female ApoE4 homozygotes with Lewy body (LB) pathology were more likely to experience psychosis compared to female ApoE4 non‐carriers, whereas in males there was no dose‐dependent difference (Kim et al., 2017). The objective of this study was to refine our previous findings by adjusting for covariates (age, education, MMSE scores). Method The patient cohort was obtained from the National Alzheimer’s Coordinating Center (NACC). Demographics, APOE genotype, LB pathology, and Neuropsychiatric Inventory (NPI) data was gathered in individuals with neuropathologically‐confirmed AD (n = 1,241). Patients were considered psychotic if they scored positively for delusions and/or hallucinations on the NPI. Two cohorts were extracted, those with LB pathology (LB(+)) and those without (LB(‐)). Within each cohort, patients were classified as E4(‐), E4, or E44 based on the number of APOE ε4 alleles they carried (0, 1, 2, respectively), and stratified by sex. Binary logistic regression was used to predict the relationship between ApoE4 status and sex on presence of psychosis. Result In the LB(+) group, female ApoE4 homozygotes were significantly more likely to experience psychosis compared to female ApoE4 non‐carriers (p = .003). The significant effect remained after adjusting for covariates (p = .027). There was no significant association between ApoE4 and presence of psychosis in males. In the LB(‐) group, there was no significant association between ApoE4 and presence of psychosis in either sex. There was no significant effect in female nor male ApoE4 heterozygotes, with or without LB pathology. Conclusion Sex and zygosity modulate the effect of ApoE4 on psychosis in a cohort of neuropathologically‐confirmed AD patients, specifically, that the effect of having 2 ApoE4 alleles on presence of psychosis is limited to female ApoE4 homozygotes with LB pathology. These findings reveal a cohort of AD patients that appear to be particularly vulnerable to developing psychosis. References: Kim, J., Fischer, C.E., Schweizer, T.A., & Munoz, D.G. (2017). Gender and pathology‐specific effect of Apolipoprotein E genotype on psychosis in Alzheimer’s disease. Current Alzheimer Research, 14(8), 834‐840.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 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".