Is late-life vulnerability to cardiovascular disease risk associated with longitudinal tau accumulation in older adults with mild cognitive impairment?
Bibliographic record
Abstract
Background: Older females have higher Alzheimer's Disease (AD) risk and tau burden, especially in early disease stages, compared to males. Overlapping cardiovascular disease (CVD) and dementia risk factors, like the apolipoprotein (APOE)-ε4 allele, show mixed sex-specific results. We previously found that late-life CVD risk related more strongly to tau at a single timepoint in cognitively normal, older female APOE-ε4 carriers than in males. Objectives: Do composite and component CVD risk factors explain sex differences in tau accumulation in older adults with mild cognitive impairment (MCI) and underlying amyloid-beta (Aβ) pathology? Design: Longitudinal analysis in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Setting: ADNI is a multi-site longitudinal study across the United States and Canada. Participants: = 52 older adults (aged 60-90), designated as both Aβ-positive and MCI. Measurements: CVD risk was measured by body mass index (BMI) and FRS, which includes age, systolic blood pressure (BP), high-density lipoprotein (HDL), total cholesterol, hypertension treatment, smoking, and diabetes. Regional standardized uptake value ratios (SUVRs) were extracted at each tau-PET timepoint. Composite SUVRs for Braak34 and Braak56 were calculated. Statistical models examined the separate and interactive effects of sex and APOE-ε4 on tau accumulation, and moderating effects of FRS, its components, or BMI, on tau accumulation. Results: Females accumulated more tau than males in bilateral Braak34 and right Braak56, while APOE-ε4 carriers trended toward more tau accumulation in left Braak56. FRS and its components did not relate to tau accumulation, nor influence sex effects, although they attenuated APOE-ε4 effects. In left Braak56, higher baseline BMI in males showed a trend toward greater tau accumulation. Conclusions: In MCI and Aβ-positive older adults, females accumulated more tau than males, and late-life vascular risk did not explain this relationship. Higher BMI related to more tau accumulation in males only, suggesting sex-specific vulnerability to BMI on brain health. Although replication in larger and more representative cohorts is needed, these findings corroborate accelerated tau progression in older females, independent of CVD risk, and suggest that vascular health has limited influence on tau progression once AD pathology is established in the brain.
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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 | 0.004 |
| 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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".