APOE-ε4 modulates the association among plasma Aβ42/Aβ40, vascular diseases, neurodegeneration and cognitive decline in non-demented elderly adults
Bibliographic record
Abstract
Abstract Including apolipoprotein E-ε4 (APOE-ε4) status and older age into consideration may increase the accuracy of plasma Aβ 42 /Aβ 40 detecting Aβ+ individuals, but the rationale behind this remains to be fully understood. Besides, both Aβ pathology and vascular diseases are related to neurodegeneration and cognitive decline, but it is still not fully understood how APOE-ε4 modulates these relationships. In this study, we examined 241 non-demented Alzheimer’s Disease Neuroimaging Initiative participants to investigate the associations among age, white matter hyperintensities (WMH), hypertension, hyperlipidemia, body mass index (BMI), plasma Aβ 42 /Aβ 40 measured by liquid chromatography tandem mass spectrometry, and 18 F-florbetapir Aβ PET as well as their prediction of longitudinal adjusted hippocampal volume (aHCV) and cognition in APOE-ε4 carriers and non-carriers. We found older age predicted faster WMH increase ( p = 0.024) and cortical Aβ accumulation ( p = 0.043) in APOE-ε4 non-carriers only, whereas lower plasma Aβ 42 /Aβ 40 predicted faster cortical Aβ accumulation ( p < 0.018) regardless of APOE-ε4 status. While larger WMH and underweight predicted ( p < 0.05) faster decreases in aHCV and cognition in APOE-ε4 non-carriers, lower plasma Aβ 42 /Aβ 40 predicted ( p < 0.031) faster decreases in aHCV and cognition in APOE-ε4 carriers. Higher Aβ PET also predicted faster rates of aHCV ( p = 0.010) in APOE-ε4 carriers only, but was related to faster rates of cognitive decline ( p < 0.022) regardless of APOE-ε4 status. These findings may provide novel insights into understanding different mechanisms underlie neurodegeneration and cognitive decline in non-demented elderly adults with and without APOE-ε4 allele, which may help the design of anti-Alzheimer’s clinical trials.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.000 | 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 teacher head, 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".