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Antihypertensive Medication Class and Incident Alzheimers Disease and Related Dementias: External Replication Across Two Independent Healthcare Data Sources-the Vanderbilt EHR Synthetic Derivative and US Medicare Claims
Tiwari, A.; Chen, R.; Tan, Y.; Yan, Y.; Wen, Z.; Wei, W.-Q.; Zhong, X.; Li et al.. medRxiv (preprint), 2026-09-17
Topic: Amyloid, tau and blood-test diagnosis
ObjectiveTo externally replicate and extend prior findings across two structurally independent healthcare data sources, evaluating whether predominant use of antihypertensive medications that stimulate versus inhibit angiotensin II type 2 and type 4 receptor signaling is associated with risk of incident ADRD. After adjustment, predominant use of stimulating medications was associated with lower ADRD risk versus inhibiting medications in both cohorts (Medicare: HR, 0.92; 95% CI, 0.90-0.93; P < .001; VUMC SD: HR, 0.92; 95% CI, 0.85-0.99; P = .03). Conclusions and RelevanceAcross two structurally independent data sources, the predominant use of antihypertensive medications that stimulate angiotensin II type 2 and type 4 receptor signaling was associated with a modestly lower risk of incident ADRD compared with predominantly inhibiting agents. By replicating in two distinct data environments, these findings extend prior single-source pharmacoepidemiologic evidence and support evaluation of receptor-targeted antihypertensive strategies for cognitive outcomes in randomized comparative-effectiveness trials.
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APA 7th
Tiwari, A., Chen, R., Tan, Y., Yan, Y., Wen, Z., Wei, W.-Q., et al. (2026). Antihypertensive Medication Class and Incident Alzheimers Disease and Related Dementias: External Replication Across Two Independent Healthcare Data Sources-the Vanderbilt EHR Synthetic Derivative and US Medicare Claims. medRxiv (preprint). https://doi.org/10.64898/2026.09.11.26362859
Vancouver
Tiwari A, Chen R, Tan Y, Yan Y, Wen Z, Wei W.-Q, et al. Antihypertensive Medication Class and Incident Alzheimers Disease and Related Dementias: External Replication Across Two Independent Healthcare Data Sources-the Vanderbilt EHR Synthetic Derivative and US Medicare Claims. medRxiv (preprint). 2026. doi:10.64898/2026.09.11.26362859.
BibTeX
@article{tiwari2026-334d2e2d,
author = {Tiwari, A. and Chen, R. and Tan, Y. and Yan, Y. and Wen, Z. and Wei, W.-Q. and Zhong, X. and Li and others},
title = {{Antihypertensive Medication Class and Incident Alzheimers Disease and Related Dementias: External Replication Across Two Independent Healthcare Data Sources-the Vanderbilt EHR Synthetic Derivative and US Medicare Claims}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.09.11.26362859},
url = {https://doi.org/10.64898/2026.09.11.26362859}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- ObjectiveTo externally replicate and extend prior findings across two structurally independent healthcare data sources, evaluating whether predominant use of antihypertensive medications that stimulate versus inhibit angiotensin II type 2 and type 4 receptor signaling is associated with risk of inci
- After adjustment, predominant use of stimulating medications was associated with lower ADRD risk versus inhibiting medications in both cohorts (Medicare: HR, 0.92; 95% CI, 0.90-0.93; P < .001; VUMC SD: HR, 0.92; 95% CI, 0.85-0.99; P = .03).
- Conclusions and RelevanceAcross two structurally independent data sources, the predominant use of antihypertensive medications that stimulate angiotensin II type 2 and type 4 receptor signaling was associated with a modestly lower risk of incident ADRD compared with predominantly inhibiting agents.
- By replicating in two distinct data environments, these findings extend prior single-source pharmacoepidemiologic evidence and support evaluation of receptor-targeted antihypertensive strategies for cognitive outcomes in randomized comparative-effectiveness trials.
Why it matters
Across two large healthcare databases, people who mainly took blood pressure medications that stimulate certain angiotensin receptors had a modestly lower risk of developing Alzheimer's disease and related dementias than those taking inhibiting types. This is observational evidence only, and the authors say randomized trials are needed before any treatment recommendations can be made.
New to this subject? Start with our plain-English guide: Alzheimer's in numbers →
Study details
- Study designcohort study
- Participants1,596,034
- Effect size6.7%; 8.2%; 4.9%
- Evidence strengthHigh
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 41 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 39 of the 94 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 4 / 4 | 1,596,034 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Bingshan Li: h-index 49 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Emory University: institution h-index 1,360 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 39 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 39 of the 94 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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