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Data-driven discovery of associations between prescribed drugs and dementia risk: A systematic review

Lookup NU author(s): Dr Eugene TangORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2025 The Author(s). Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.Abstract: Recent clinical trials on slowing dementia progression have led to renewed focus on finding safer, more effective treatments. One approach to identify plausible candidates is to assess whether existing medications for other conditions may affect dementia risk. We conducted a systematic review to identify studies adopting a data-driven approach to investigate the association between a wide range of prescribed medications and dementia risk. We included 14 studies using administrative or medical records data for more than 130 million individuals and 1 million dementia cases. Despite inconsistencies in identifying specific drugs that may modify Alzheimer's or dementia risk, some themes emerged for drug classes with biological plausibility. Antimicrobials, vaccinations, and anti-inflammatories were associated with reduced risk, while diabetes drugs, vitamins and supplements, and antipsychotics were associated with increased risk. We found conflicting evidence for antihypertensives and antidepressants. Drug repurposing for use in dementia is an urgent priority. Our findings offer a basis for prioritizing candidates and exploring underlying mechanisms. Highlights: ·We present a systematic review of studies reporting association between drugs prescribed for other conditions and risk of dementia including 139 million people and 1 million cases of dementia. ·Our work supports some previously reported associations, for example, showing decreased risk of dementia with drugs to treat inflammatory disease and increased risk with antipsychotic treatment. ·Antimicrobial treatment was perhaps more surprisingly associated with decreased risk, supportive of recent increased interest in this potential therapeutic avenue. ·Our work should help prioritize drugs for entry into adaptive platform trials in Alzheimer's disease and will serve as a useful resource for those investigating drugs or classes of drugs and risk of dementia.

Publication metadata

Author(s): Underwood BR, Lourida I, Gong J, Tamburin S, Tang EYH, Sidhom E, Tai XY, Betts MJ, Ranson JM, Zachariou M, Olaleye OE, Das S, Oxtoby NP, Chen S, Llewellyn DJ, Deep Dementia Phenotyping (DEMON) Network

Publication type: Review

Publication status: Published

Journal: Alzheimer's and Dementia: Translational Research and Clinical Interventions

Year: 2025

Volume: 11

Issue: 1

Print publication date: 01/01/2025

Online publication date: 21/01/2025

Acceptance date: 09/12/2024

ISSN (electronic): 2352-8737

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1002/trc2.70037

DOI: 10.1002/trc2.70037

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