Home › Research › Drug development
Effect of initiating an ARB- versus ACEI-based regimen on dementia risk, a target trial emulation of 2.5 million US Veterans
Xu Y, Shi J, Andrews R, Derington CG, Greene T, Scharfstein D, Berchie R, Supiano M et al.. medRxiv, 2026-07-08
Topic: Drug trials: efficacy and safety
Among 2,577,000 Veterans (mean age, 63 years; 4.5% female; 65% White; 15% Black), 10% initiated ARBs and 90% initiated ACEIs. Over five years of follow up, 6% developed dementia, 12% died without dementia, and 13% died overall. ARB initiation yielded consistently lower risk of dementia (risk ratio, 0.88; 95% CI, 0.83-0.93 at 6 months to 0.92; 95% CI, 0.90-0.94 at 5 years) and dementia-free death (risk ratio, 0.90; 95% CI, 0.86-0.96 at 6 months to 1.00; 95% CI, 0.98-1.01 at 5 years) than ACEI initiation. Effects on secondary outcomes were similar to those for primary outcomes. Greater protective dementia effects were observed in older and male Veterans and non-statin users, with similar effects on dementia-free death. Among US Veterans with incident treated hypertension, initiation of ARB versus ACEI antihypertensive regimen conveyed a modestly lower risk of dementia. Given the high prevalence of hypertension, these modest effects may confer meaningful population-level benefits on brain health. Future research estimating per-protocol effects using a more generalizable population is needed to confirm our findings. Key words: antihypertensive medication, dementia, natural language processing, target trial emulation, Veteran
Key findings
- Among 2,577,000 Veterans (mean age, 63 years; 4.5% female; 65% White; 15% Black), 10% initiated ARBs and 90% initiated ACEIs.
- Over five years of follow up, 6% developed dementia, 12% died without dementia, and 13% died overall.
- ARB initiation yielded consistently lower risk of dementia (risk ratio, 0.88; 95% CI, 0.83-0.93 at 6 months to 0.92; 95% CI, 0.90-0.94 at 5 years) and dementia-free death (risk ratio, 0.90; 95% CI, 0.86-0.96 at 6 months to 1.00; 95% CI, 0.98-1.01 at 5 years) than ACEI initiation.
- Effects on secondary outcomes were similar to those for primary outcomes.
- Greater protective dementia effects were observed in older and male Veterans and non-statin users, with similar effects on dementia-free death.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Study designlongitudinal study
- Participants2,577,000
- Effect size4.5%
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 50 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 times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 31 of the 62 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 2,577,000 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| 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 | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 31 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 31 of the 62 points we could judge it on is 50 out of 100. |
| Total | 50 / 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
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Xu, Y., Shi, J., Andrews, R., Derington, C. G., Greene, T., Scharfstein, D., et al. (2026). Effect of initiating an ARB- versus ACEI-based regimen on dementia risk, a target trial emulation of 2.5 million US Veterans. medRxiv. https://doi.org/10.64898/2026.07.05.26357173
Vancouver
Xu Y, Shi J, Andrews R, Derington CG, Greene T, Scharfstein D, et al. Effect of initiating an ARB- versus ACEI-based regimen on dementia risk, a target trial emulation of 2.5 million US Veterans. medRxiv. 2026. doi:10.64898/2026.07.05.26357173.
BibTeX
@article{xu2026-e1b89ac2,
author = {Xu, Y. and Shi, J. and Andrews, R. and Derington, C. G. and Greene, T. and Scharfstein, D. and Berchie, R. and Supiano, M. and others},
title = {{Effect of initiating an ARB- versus ACEI-based regimen on dementia risk, a target trial emulation of 2.5 million US Veterans}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.07.05.26357173},
url = {https://doi.org/10.64898/2026.07.05.26357173}
}
Related studies in Drug development
Also tagged “cholinesterase”
271 studies in the library carry the topic tag “cholinesterase”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 271 tagged studies.