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Impact of Different Antihypertensive Drug Classes on Incident Dementia in Older Adults: A Systematic Review and Meta-Analysis
Lu Ding, Meng Zhang, Huihong Wu, Xiangzhao Wang, Xiaojie Zhu, Zixin Chen, Yuanxi Zhang, Ziwang Liu. Journal of the American Medical Directors Association, 2026-04-21
Topic: Risk, prevention and care in population studies
Objectives To evaluate the association between different classes of antihypertensive medications (AHMs) and dementia risk in older adults through systematic review and meta-analysis. Design Systematic review and exploratory network meta-analysis (NMA) following PRISMA-MOOSE guidelines. For traditional meta-analysis, random-effects models (DerSimonian-Laird method) were used for dichotomous outcomes, and fixed-effects models for continuous outcomes. Exploratory NMA employed a frequentist fixed-effects model (Stata 18 network package), as the sparse network precluded Bayesian estimation. Setting and participants Four multicenter randomized controlled trials [Syst-Eur, Perindopril Protection Against Recurrent Stroke Study (PROGRESS), SCOPE, HYVET-COG] comprising 16,823 hypertensive older adults without dementia at baseline, with follow-up durations of 2.0-3.9 years. Methods Literature searches were conducted in PubMed, Cochrane Library, Web of Science, and Embase from inception to December 31, 2025. Risk of bias was assessed using Cochrane RoB 2, and evidence certainty was evaluated using GRADE. Random-effects models pooled dichotomous outcomes [odds ratios (OR)] and fixed-effects models analyzed continuous outcomes [standardized mean differences (SMDs)]. Results Antihypertensive treatment significantly improved cognitive function scores (SMD, 0.06; 95% CI, 0.03-0.09; P Conclusions and implications Antihypertensive therapy significantly improves cognitive function with moderate certainty evidence, supporting its use for cognitive protection in older adults with hypertension. The trend toward dementia risk reduction, although uncertain, suggests potential long-term benefits warranting further investigation. Clinical implications These findings support optimizing antihypertensive regimens for dementia prevention in high-risk populations, with drug class selection informed by specific treatment goals (dementia prevention vs cognitive maintenance). Policy and research implications Current evidence is limited by few studies and short follow-up; large-scale randomized controlled trials with dementia as a primary endpoint, head-to-head drug class comparisons, and inclusion of long-term care residents-who bear the highest disease burden yet are underrepresented in trials-are urgently needed to inform precision prescribing guidelines.
Key findings
- Results Antihypertensive treatment significantly improved cognitive function scores (SMD, 0.06; 95% CI, 0.03-0.09; P < .001, GRADE moderate certainty) and showed a nonsignificant trend toward reduced dementia incidence (OR, 0.89; 95% CI, 0.76-1.05; P = .172, GRADE low certainty).
- Clinical implications These findings support optimizing antihypertensive regimens for dementia prevention in high-risk populations, with drug class selection informed by specific treatment goals (dementia prevention vs cognitive maintenance).
Why it matters
Pooling four randomized trials of older adults with high blood pressure, antihypertensive treatment improved cognitive function scores with moderate-certainty evidence. The analysis supports using antihypertensives for cognitive protection, but the authors note the drug-class network was sparse and call for optimizing regimens rather than naming one best class.
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Study details
- Study designmeta-analysis
- Participants16,823
- Effect sizeCognitive function SMD 0.06 (95% CI 0.03-0.09); dementia incidence OR 0.89 (95% CI 0.76-1.05)
- Evidence strengthModerate
Limitations
Only four trials with short follow-up; the network meta-analysis has a single trial per drug class, so rankings are unreliable; long-term care residents under-represented.
How this study scored 58/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. We have no data on free to read, so that was left out: it earned 57 of the 98 points we could judge it on, which is 58 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of the American Medical Directors Association) |
| Journal's citation record | 2 / 4 | Journal of the American Medical Directors Association: journal h-index 172 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 4 / 4 | 16,823 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 2 / 6 | Cited 2.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Yang Liu: h-index 25 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Beijing University of Chinese Medicine: institution h-index 298 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41962914) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 57 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 57 of the 98 points we could judge it on is 58 out of 100. |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Ding, L., Zhang, M., Wu, H., Wang, X., Zhu, X., Chen, Z., et al. (2026). Impact of Different Antihypertensive Drug Classes on Incident Dementia in Older Adults: A Systematic Review and Meta-Analysis. Journal of the American Medical Directors Association. https://doi.org/10.1016/j.jamda.2026.106185
Vancouver
Ding L, Zhang M, Wu H, Wang X, Zhu X, Chen Z, et al. Impact of Different Antihypertensive Drug Classes on Incident Dementia in Older Adults: A Systematic Review and Meta-Analysis. Journal of the American Medical Directors Association. 2026. doi:10.1016/j.jamda.2026.106185. PMID: 41962914.
BibTeX
@article{ding2026-41962914,
author = {Ding, Lu and Zhang, Meng and Wu, Huihong and Wang, Xiangzhao and Zhu, Xiaojie and Chen, Zixin and Zhang, Yuanxi and Liu, Ziwang},
title = {{Impact of Different Antihypertensive Drug Classes on Incident Dementia in Older Adults: A Systematic Review and Meta-Analysis}},
journal = {Journal of the American Medical Directors Association},
year = {2026},
doi = {10.1016/j.jamda.2026.106185},
pmid = {41962914},
url = {https://doi.org/10.1016/j.jamda.2026.106185}
}
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