P3‐266: Gender modifying‐effect between APOE and cognitive decline in Alzheimer's disease: The Cache County dementia progression study
Bibliographic record
Abstract
Apolipoprotein E e4 (APOE e4) is awell-established risk factor for the development of Alzheimer's disease (AD). However, the association between APOE genotype and rate of progression in patients with AD remains controversial. Some studies suggest that presence of APOE e4 leads to faster cognitive decline, slower decline, or even that APOE genotype is not associated with decline. Among incident cases of AD in the population-based Cache County Dementia Progression study, APOE genotype was examined as a predictor of both pre- and post-AD trajectories of MMSE. Mixed effect models were estimated to assess this relationship, treating subject-specific intercepts and linear change with time as random effects. MMSEtrajectories from 335 incident cases (65.6% female; 45.1% APOE E4 carriers)were analyzed. While there was no association of APOE e4 status with cognitive decline at the pre-dementia onset phase of the disease, there was significant association during the post-onset phase. This relationship depended on gender and time from reported onset of symptoms. At the early post-onset phase of the disease, men who were e4 carriers declined faster than men who were non-carriers; women who were carriers decline slower than women who were non-carriers. As the disease progressed, differences in the rate of decline by gender and APOE genotype were no longer significant. For example,1 year after an AD diagnosis, the rate of decline of women e4 carriers was significantly different from both men and women who are non-carriers. However, five years after an AD diagnosis, the only statistically significant difference in the rate of declineis between women non-carriers and men carriers. After 8 years, all differences in rate of decline among carriers and non-carriers of both genders have disappeared. These findings demonstrate that the effect of APOE genotype on the rate of cognitive decline has a complex structure and depends on gender and also on the duration following the onset of AD. These results may help explain the differences in the literature regarding the effect of APOE on the rate of decline.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 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".