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Systemic medications and dementia risk: a systematic umbrella review
Clara Belessiotis-Richards1,2, Joseph Hayes3,4, Ying Feng Yap5,6
1Division of Psychiatry, University College London, London, United Kingdom. c.belessiotis@ucl.ac.uk.
Molecular Psychiatry
|July 24, 2025
Summary
Systemic medications like anti-hypertensives and statins may reduce dementia risk, while anticholinergics may increase it. Proactive hypertension treatment is recommended, but drug repurposing for dementia prevention requires more evidence.
Area of Science:
- Neurology
- Pharmacology
- Epidemiology
Background:
- Previous meta-analyses suggest systemic medications can influence dementia risk.
- An overview of existing evidence is needed for clinical guidance and research direction.
Purpose of the Study:
- To conduct an umbrella review of meta-analyses on systemic medications and dementia risk.
- To synthesize evidence to inform clinical practice and future research priorities.
Main Methods:
- Umbrella review of 68 meta-analyses (PROSPERO CRD42021226307) from inception to April 2024.
- Inclusion of peer-reviewed meta-analyses on dementia risk and systemic medications in humans.
- Quality assessment using AMSTAR-2 and certainty of evidence rated using GRADE.
Main Results:
- Moderate certainty evidence suggests reduced dementia risk with anti-hypertensives, statins, SGLT2 inhibitors, and GLP-1 RAs.
- Moderate certainty evidence suggests increased dementia risk with anticholinergics.
- Observational data dominated, with limitations including confounding and reverse causality; RCT data supported hypertension treatment benefits.
Conclusions:
- Insufficient evidence currently supports repurposing systemic drugs solely for dementia risk reduction.
- Proactive hypertension management is recommended to lower all-cause dementia risk.
- Avoidance of anticholinergic drugs in cognitive impairment is advised, with assessment of burden and consideration of alternatives.
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