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

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 revi...

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Main Authors: Benjamin R. Underwood, Ilianna Lourida, Jessica Gong, Stefano Tamburin, Eugene Yee Hing Tang, Emad Sidhom, Xin You Tai, Matthew J. Betts, Janice M. Ranson, Margarita Zachariou, Olajide E. Olaleye, Saswati Das, Neil P. Oxtoby, Shanquan Chen, David J. Llewellyn, for the Deep Dementia Phenotyping (DEMON) Network
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Alzheimer’s & Dementia: Translational Research & Clinical Interventions
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Online Access:https://doi.org/10.1002/trc2.70037
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author Benjamin R. Underwood
Ilianna Lourida
Jessica Gong
Stefano Tamburin
Eugene Yee Hing Tang
Emad Sidhom
Xin You Tai
Matthew J. Betts
Janice M. Ranson
Margarita Zachariou
Olajide E. Olaleye
Saswati Das
Neil P. Oxtoby
Shanquan Chen
David J. Llewellyn
for the Deep Dementia Phenotyping (DEMON) Network
author_facet Benjamin R. Underwood
Ilianna Lourida
Jessica Gong
Stefano Tamburin
Eugene Yee Hing Tang
Emad Sidhom
Xin You Tai
Matthew J. Betts
Janice M. Ranson
Margarita Zachariou
Olajide E. Olaleye
Saswati Das
Neil P. Oxtoby
Shanquan Chen
David J. Llewellyn
for the Deep Dementia Phenotyping (DEMON) Network
author_sort Benjamin R. Underwood
collection DOAJ
description 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.
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spelling doaj-art-ffb14b42a136443bb99e21bb9bab7c592025-08-20T02:10:06ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372025-01-01111n/an/a10.1002/trc2.70037Data‐driven discovery of associations between prescribed drugs and dementia risk: A systematic reviewBenjamin R. Underwood0Ilianna Lourida1Jessica Gong2Stefano Tamburin3Eugene Yee Hing Tang4Emad Sidhom5Xin You Tai6Matthew J. Betts7Janice M. Ranson8Margarita Zachariou9Olajide E. Olaleye10Saswati Das11Neil P. Oxtoby12Shanquan Chen13David J. Llewellyn14for the Deep Dementia Phenotyping (DEMON) NetworkDepartment of Psychiatry and Cambridgeshire and Peterborough NHS Foundation Trust, Windsor Unit Fulbourn Hospital Cambridge University of Cambridge Cambridge UKNIHR Applied Research Collaboration South West (PenARC) University of Exeter Exeter UKDepartment of Epidemiology and Public Health University College London London UKDepartment of Neurosciences, Biomedicine and Movement Sciences University of Verona Verona ItalyPopulation Health Sciences Institute Newcastle University Newcastle UKDepatment of Clinical neurosciences University of Cambridge, and Cambridge and Peterborough NHS Foundation Trust, Windsor Unit, Fulbourn Hospital Cambridge UKNuffield Department of Clinical Neurosciences University of Oxford Oxford UKInstitute of Cognitive Neurology and Dementia Research Otto‐von‐Guericke University Magdeburg Magdeburg GermanyDepartment of Health and Community Sciences, Medical School University of Exeter Exeter UKBioinformatics Department The Cyprus Institute of Neurology and Genetics Nicosia CyprusDepartment of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USAAtal Bihari Vajpayee Institute of Medical Sciences & Dr Ram Manohar Lohia Hospital New Delhi IndiaUCL Centre for Medical Image Computing Department of Computer Science University College London London UKInternational Centre for Evidence in Disability London School of Hygiene & Tropical Medicine London UKDepartment of Health and Community Sciences, Medical School University of Exeter Exeter UKAbstract 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.https://doi.org/10.1002/trc2.70037medicationsdrug repurposingelectronic health recordsmachine learningpharmacoepidemiologydementia
spellingShingle Benjamin R. Underwood
Ilianna Lourida
Jessica Gong
Stefano Tamburin
Eugene Yee Hing Tang
Emad Sidhom
Xin You Tai
Matthew J. Betts
Janice M. Ranson
Margarita Zachariou
Olajide E. Olaleye
Saswati Das
Neil P. Oxtoby
Shanquan Chen
David J. Llewellyn
for the Deep Dementia Phenotyping (DEMON) Network
Data‐driven discovery of associations between prescribed drugs and dementia risk: A systematic review
Alzheimer’s & Dementia: Translational Research & Clinical Interventions
medications
drug repurposing
electronic health records
machine learning
pharmacoepidemiology
dementia
title Data‐driven discovery of associations between prescribed drugs and dementia risk: A systematic review
title_full Data‐driven discovery of associations between prescribed drugs and dementia risk: A systematic review
title_fullStr Data‐driven discovery of associations between prescribed drugs and dementia risk: A systematic review
title_full_unstemmed Data‐driven discovery of associations between prescribed drugs and dementia risk: A systematic review
title_short Data‐driven discovery of associations between prescribed drugs and dementia risk: A systematic review
title_sort data driven discovery of associations between prescribed drugs and dementia risk a systematic review
topic medications
drug repurposing
electronic health records
machine learning
pharmacoepidemiology
dementia
url https://doi.org/10.1002/trc2.70037
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