P4‐319: Apoe Genotype, Serum Plasmalogens, Brain Amyloid and Tangles, and Cognition: a Pre‐/Post‐Mortem Analysis in Elderly Persons
Bibliographic record
Abstract
Apolipoprotein E (APOE) genotype, serum plasmalogen (PlsEtn) levels, and brain amyloid and tangle densities have previously been associated with cognitive status in independent studies. The association between ApoE genotype, pre-mortem serum PlsEtn, and post-mortem brain amyloid and tangle density and cognition in elderly persons was investigated. Serum PlsEtn, APOE genotype and cognition were determined in 1743 living persons aged 58-104 (85.2+/-7.4, Rush University Religious Orders Study and Memory and Aging Project). Of these persons, 847 have since deceased. The average time to death from the collection of cognition and serum PlsEtn was 1.6+/-1.6 years. In deceased persons, a chart review was performed to determine the person’s diagnostic status at time of death [no cognitive impairment (NCI), mild cognitive impairment (MCI) or Alzheimer’s Disease (AD)]. A quantitative PlsEtn Biosynthesis Value (PBV) was generated for each person by combining the relative serum levels of three key PlsEtn species. Ordered regression analysis was used to determine the odds of AD in the presence of MCI. Coefficients and odds ratios of continuous variables expressed per standard deviation (SD). All models adjusted for age, education, time to death and gender. In participants who became deceased, higher PBV (coef=0.195, p<0.001) and a APOE ε2ε3 genotype (relative to ε3ε3; coef=0.320, p=0.002) were associated with higher cognition and a APOE ε3ε4/ε4ε4 genotype (relative to ε3ε3; coef=-0.446, p<0.001) was associated with lower cognition. Higher brain tangle density (coef=-0.365, p<0.001) was observed to be associated with lower cognition and higher PBV with higher cognition (coef=0.180, p<0.001). APOE genotype and post-mortem brain amyloid density was not associated with cognition after adjusting for tangles and PBV levels. Higher pre-mortem PBV and a APOE ε2ε3 genotype (relative to APOE ε3ε3) were associated with a lower odds of AD (OR=0.690, p<0.001; OR=0.584, p=0.043) and post-mortem tangle density was associated with a higher odds of AD (OR=2.29, p<0.001). APOE ε4 genotype and post-mortem brain amyloid density was not associated with cognition or diagnosis after adjusting for tangles and PBV levels. The association between PBV and cognition is independent of brain amyloid and tangle densities.
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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 | 0.000 | 0.001 |
| 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 | 0.000 | 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".