Investigating the impact of hypertension with and without diabetes on progression to Alzheimer’s disease: A clinic‐pathological study
Bibliographic record
Abstract
Abstract Background Hypertension and diabetes have each been associated with an increased risk of progression to Alzheimer’s disease (AD) dementia. Here, we investigated their combined impact on progression from cognitively normal to clinically‐diagnosed AD. Method Cognitively normal individuals from the National Alzheimer’s Coordinating Center were identified as having neither hypertension nor diabetes (HTN‐/DM‐), hypertension without diabetes (HTN+/DM‐), or hypertension with diabetes (HTN+/DM+). The presence of HTN and DM were based on their diagnosis from recent medical history or medication use. This study investigated whether HTN+/DM‐ or HTN+/DM+ were predictors of progression to clinically‐diagnosed AD compared to HTN‐/DM‐. In a subgroup analysis with post‐mortem data, we investigated whether HTN+/DM‐, and HTN+/DM+ were predictors of progression to clinically diagnosed AD due to underlying AD‐ and/or vascular neuropathology. Result This study included N = 11074 cognitively normal individuals (mean age: 71.7 (9.0), MMSE: 28.9 (1.4), male: N = 3818 (34%)). Approximately 7% (N = 830) progressed to clinically‐diagnosed AD, and the average duration of follow‐up was 5.2 (3.6) years. Forty‐two percent (N = 4608) were HTN‐/DM‐, 45% (N = 5034) were HTN+/DM‐, and 13% (N = 1432) were HTN+/DM+. Both HTN+/DM‐ (hazard ratio (HR): 1.24 (1.17‐1.32), p<.001), and HTN+/DM+ (HR: 1.31 (1.19‐1.44), p<.001) were significant predictors of progression to clinically‐diagnosed AD. Subgroup analyses with post‐mortem data (N = 919) demonstrated that compared to HTN‐/DM‐, those with HTN+/DM‐ had a higher risk of progressing to clinically‐diagnosed AD with underlying cerebrovascular disease (CVD) neuropathology (HR: 1.54 (1.17‐2.03), p = .002), whereas those with HTN+/DB+ had a higher risk of progression to clinically‐diagnosed AD with underlying AD (HR: 2.10 (1.16‐3.79), p = .01) and cerebral amyloid angiopathy (CAA) neuropathology (HR: 1.52 (1.09‐2.12), p = .01). Conclusion These findings demonstrate that underlying CVD neuropathology contributes to the risk of clinically‐diagnosed AD in individuals with HTN+/DM‐, while both AD and CAA neuropathology contributes to the risk of clinically‐diagnosed AD in individuals with HTN+/DM+. This suggests that individuals with HTN+/DM‐ and HTN+/DM+ vary phenotypically and may warrant the need for different treatment strategies to reduce the future risk of 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 | 0.001 | 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 | 0.001 | 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".