Vascular risk factors modulate the association between amyloid and tau PET in cognitively normal patients
Bibliographic record
Abstract
BACKGROUND: Vascular risk factors have been associated with increased risk of Alzheimer's disease (AD) dementia. Previous studies showed mixed and complex interactions between vascular pathology and AD. In a longitudinal study of cognitively normal participants, we evaluated whether individual vascular risk factors are associated with amyloid and/or tau burden. We also investigated whether these factors and their treatments influence the association between amyloid and tau pathology. METHODS: We performed [18F]-NAV4694 and [18F]-AV1451 positron emission tomography on 241 older adults (age 68.3 ± 5.1 years, 69.3% female) from the PREVENT-AD cohort. All participants had been cognitively unimpaired at baseline. Longitudinal scans were available for 115 persons (4.4 ± 0.6 years follow-up). We examined the association between individual vascular factors (ApoE status, BMI, cholesterol, blood pressure) and global Aβ and/or temporal META-ROI tau burden, as well as their annual change. We then examined two-way interactions between global Aβ and these vascular factors (using clinical-categorical measures) or treatments as predictors of tau burden. Finally, we explored three-way interactions that included both vascular factors and medical treatments. All analyses were adjusted for age, sex, and education. RESULTS: Among the individual vascular risk factors, only ApoE4 status was significantly associated with amyloid burden (p < 0.001) and its annual change (p = 0.002). ApoE4 status also predicted tau burden (p < 0.001), but its association with annual change in tau was at a trend level (p = 0.088; not shown). At abnormal levels of HDL cholesterol, and diastolic blood pressure, there was a stronger increase in temporal Meta-ROI tau-PET at any given level of amyloid PET (Figure 1). Furthermore, stronger amyloid-related increase in tau was observed in patients untreated for hypertension but not treated patients (Figure 2). Three-way interactions showed that HDL cholesterol and diastolic blood pressure were modulatory factors only in the hypertension untreated patients, suggesting that hypertension treatment alleviates the influence of vascular risk factors on tau pathology (Figure 3). CONCLUSIONS: Hyperlipidemia and hypertension, if untreated, are associated with accelerated amyloid related increase in tau pathology in AD.
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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 | 0.002 |
| 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 | 0.001 | 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".