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Systemic medications and dementia risk: a systematic umbrella review
Belessiotis-Richards C, Hayes J, Feng Yap Y, Talwar S, Eskinazi M, Li W, Ward H, Letrondo PA et al.. Molecular psychiatry, 2025-07-24
Topic: Risk, prevention and care in population studies
Background Previous meta-analyses have found that systemic medications may modulate dementia risk. We aimed to provide an overview of this evidence to guide clinical practice and future research. Methods We conducted an umbrella review of meta-analyses (PROSPERO CRD42021226307), searching databases from inception to 15th April 2024. Only peer-reviewed meta-analyses examining dementia risk and systemic medications in humans were included. Two authors independently screened studies for inclusion, extracted study data and assessed quality of meta-analyses using the AMSTAR-2 tool. Three authors independently rated the certainty of evidence for each drug using the GRADE framework. Results 68 meta-analyses were included, across 11 drug categories. Across meta-analyses, available data were primarily observational. Confounding by indication and potential reverse causality were important limitations. Randomised-controlled data were rare but supported an association between treatment of hypertension and reduced dementia incidence. Overall, we found moderate certainty evidence of reduced risk of dementia associated with anti-hypertensives, statins, sodium-glucose transport protein 2 (SGLT2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and moderate certainty of increased risk with anticholinergics. Discussion Currently, there is insufficient evidence to advise repurposing any systemic drugs with the primary aim of reducing dementia risk. On the basis of our findings, we recommend proactive treatment of hypertension to reduce risk of all-cause dementia. Our findings did not find a difference between antihypertensive drug classes, but dementia risk was associated with blood pressure reading. In addition, we advise avoidance of anticholinergic drugs in cognitive impairment, with assessment of anticholinergic burden and consideration of alternatives during routine clinical contacts.
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APA 7th
Belessiotis-Richards, C., Hayes, J., Feng Yap, Y., Talwar, S., Eskinazi, M., Li, W., et al. (2025). Systemic medications and dementia risk: a systematic umbrella review. Molecular psychiatry. https://doi.org/10.1038/s41380-025-03129-3
Vancouver
Belessiotis-Richards C, Hayes J, Feng Yap Y, Talwar S, Eskinazi M, Li W, et al. Systemic medications and dementia risk: a systematic umbrella review. Molecular psychiatry. 2025. doi:10.1038/s41380-025-03129-3. PMID: 40707785.
BibTeX
@article{belessiotisrichards2025-40707785,
author = {Belessiotis-Richards, C. and Hayes, J. and Feng Yap, Y. and Talwar, S. and Eskinazi, M. and Li, W. and Ward, H. and Letrondo, P. A. and others},
title = {{Systemic medications and dementia risk: a systematic umbrella review}},
journal = {Molecular psychiatry},
year = {2025},
doi = {10.1038/s41380-025-03129-3},
pmid = {40707785},
url = {https://doi.org/10.1038/s41380-025-03129-3}
}
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Key findings
- Results 68 meta-analyses were included, across 11 drug categories.
- Overall, we found moderate certainty evidence of reduced risk of dementia associated with anti-hypertensives, statins, sodium-glucose transport protein 2 (SGLT2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and moderate certainty of increased risk with anticholinergics.
- On the basis of our findings, we recommend proactive treatment of hypertension to reduce risk of all-cause dementia.
- Our findings did not find a difference between antihypertensive drug classes, but dementia risk was associated with blood pressure reading.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 76/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it. We have no data on journal's citation record, 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 multicenter collaboration, so those were left out: it earned 44 of the 58 points we could judge it on, which is 76 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | A review of other studies — randomization is not credited here |
| 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40707785) |
| Free to read | 2 / 2 | Free to read |
| Points | 44 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 44 of the 58 points we could judge it on is 76 out of 100. |
| Total | 76 / 100 | — |
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