{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:10:21Z","timestamp":1791598221217,"version":"4.3.4"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01 DA045705-S1"],"award-info":[{"award-number":["R01 DA045705-S1"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["K23AG066864"],"award-info":[{"award-number":["K23AG066864"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Previous findings regarding the association between benzodiazepine exposure and dementia have conflicted, though many have not accounted for anticholinergic exposure. The goal of this study was to evaluate the association of benzodiazepine exposure with the risk of developing dementia, accounting for the anticholinergic burden.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a retrospective cohort design, we identified veterans 65 or older without dementia during a 10-year baseline period and then followed participants for 5 years to evaluate the risk of dementia diagnosis. The primary exposure was cumulative benzodiazepine exposure. Cox proportional hazards survival model was used to examine the association between benzodiazepine exposure and dementia, adjusting for anticholinergic burden and other demographic and clinical characteristics associated with increased dementia risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 528 006 veterans in the study cohort, 28.5% had at least one fill for a benzodiazepine. Overall, 7.9% developed a diagnosis of dementia during the observation period. Compared to veterans with no exposure to benzodiazepines, the adjusted hazard ratios for dementia risk were 1.06 (95% confidence interval [CI] 1.02\u20131.10) for low benzodiazepine exposure, 1.05 (95% CI 1.01\u20131.09) for medium benzodiazepine exposure, and 1.05 (95% CI 1.02\u20131.09) for high benzodiazepine exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cumulative benzodiazepine exposure was minimally associated with increased dementia risk when compared with nonuse but did not increase in a dose-dependent fashion with higher exposure. Veterans with low benzodiazepine exposure had essentially the equivalent risk of developing dementia as veterans with high exposure. While benzodiazepines are associated with many side effects for older adults, higher cumulative use does not appear to increase dementia risk.<\/jats:p><\/jats:sec>","DOI":"10.1093\/gerona\/glab241","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T14:22:09Z","timestamp":1629382929000},"page":"1035-1041","source":"Crossref","is-referenced-by-count":21,"title":["Use of Benzodiazepines and Risk of Incident Dementia: A Retrospective Cohort Study"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1943-0150","authenticated-orcid":false,"given":"Lauren B","family":"Gerlach","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Michigan, Ann Arbor, USA"},{"name":"Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyungjin","family":"Myra Kim","sequence":"additional","affiliation":[{"name":"Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, USA"},{"name":"Center for Clinical Management Research, VA Ann Arbor Healthcare System, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalinda V","family":"Ignacio","sequence":"additional","affiliation":[{"name":"Center for Clinical Management Research, VA Ann Arbor Healthcare System, Michigan, USA"},{"name":"Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Strominger","sequence":"additional","affiliation":[{"name":"Center for Clinical Management Research, VA Ann Arbor Healthcare System, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donovan T","family":"Maust","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Michigan, Ann Arbor, USA"},{"name":"Center for Clinical Management Research, VA Ann Arbor Healthcare System, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"issue":"2","key":"2022050521201268900_CIT0001","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1176\/appi.ps.201800321","article-title":"Benzodiazepine use and misuse among adults in the United States","volume":"70","author":"Maust","year":"2019","journal-title":"Psychiatr Serv"},{"issue":"21","key":"2022050521201268900_CIT0002","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1001\/archinternmed.2009.357","article-title":"Meta-analysis of the impact of 9 medication classes on falls in elderly persons","volume":"169","author":"Woolcott","year":"2009","journal-title":"Arch Intern Med"},{"issue":"6","key":"2022050521201268900_CIT0003","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1176\/appi.ajp.158.6.892","article-title":"Hazardous benzodiazepine regimens in the elderly: effects of half-life, dosage, and duration on risk of hip fracture","volume":"158","author":"Wang","year":"2001","journal-title":"Am J Psychiatry"},{"issue":"2","key":"2022050521201268900_CIT0004","doi-asserted-by":"crossref","first-page":"125","DOI":"10.2165\/11539050-000000000-00000","article-title":"Effects of benzodiazepines, antidepressants and opioids on driving: a systematic review and meta-analysis of epidemiological and experimental evidence","volume":"34","author":"Dassanayake","year":"2011","journal-title":"Drug Saf"},{"issue":"4","key":"2022050521201268900_CIT0005","doi-asserted-by":"crossref","first-page":"686","DOI":"10.2105\/AJPH.2016.303061","article-title":"Increasing benzodiazepine prescriptions and overdose mortality in the United States, 1996\u20132013","volume":"106","author":"Bachhuber","year":"2016","journal-title":"Am J Public Health"},{"issue":"8","key":"2022050521201268900_CIT0006","first-page":"639","article-title":"A systematic review of amnestic and non-amnestic mild cognitive impairment induced by anticholinergic, antihistamine, GABAergic and opioid drugs","volume":"29","author":"Tannenbaum","year":"2012","journal-title":"Drugs Aging"},{"key":"2022050521201268900_CIT0007","author":"American Geriatrics Society"},{"issue":"2","key":"2022050521201268900_CIT0008","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1176\/ajp.148.2.151","article-title":"The APA task force report on benzodiazepine dependence, toxicity, and abuse","volume":"148","author":"Salzman","year":"1991","journal-title":"Am J Psychiatry"},{"key":"2022050521201268900_CIT0009","first-page":"9","article-title":"The effects of benzodiazepines on cognition","volume":"66","author":"Stewart","year":"2005","journal-title":"J Clin Psychiatry"},{"issue":"10113","key":"2022050521201268900_CIT0010","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1016\/S0140-6736(17)31363-6","article-title":"Dementia prevention, intervention, and care","volume":"390","author":"Livingston","year":"2017","journal-title":"Lancet"},{"key":"2022050521201268900_CIT0011","doi-asserted-by":"crossref","first-page":"e6231","DOI":"10.1136\/bmj.e6231","article-title":"Benzodiazepine use and risk of dementia: prospective population based study","volume":"345","author":"Billioti de Gage","year":"2012","journal-title":"BMJ"},{"issue":"sep09 2","key":"2022050521201268900_CIT0012","doi-asserted-by":"crossref","first-page":"g5205","DOI":"10.1136\/bmj.g5205","article-title":"Benzodiazepine use and risk of Alzheimer\u2019s disease: case\u2013control study","volume":"349","author":"Billioti de Gage","year":"2014","journal-title":"BMJ"},{"issue":"3","key":"2022050521201268900_CIT0013","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/1060028019882037","article-title":"Is benzodiazepine use associated with the risk of dementia and cognitive impairment\u2014not dementia in older persons? The Canadian Study of Health and Aging","volume":"54","author":"Nafti","year":"2020","journal-title":"Ann Pharmacother"},{"key":"2022050521201268900_CIT0014","doi-asserted-by":"crossref","first-page":"i90","DOI":"10.1136\/bmj.i90","article-title":"Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study","volume":"352","author":"Gray","year":"2016","journal-title":"BMJ"},{"issue":"10","key":"2022050521201268900_CIT0015","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1007\/s40264-015-0319-3","article-title":"Benzodiazepine use and risk of developing Alzheimer\u2019s disease or vascular dementia: a case\u2013control analysis","volume":"38","author":"Imfeld","year":"2015","journal-title":"Drug Saf"},{"issue":"6","key":"2022050521201268900_CIT0016","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1176\/appi.ajp.2019.19030315","article-title":"Associations of benzodiazepines, Z-drugs, and other anxiolytics with subsequent dementia in patients with affective disorders: a nationwide cohort and nested case\u2013control study","volume":"177","author":"Osler","year":"2020","journal-title":"Am J Psychiatry"},{"issue":"2","key":"2022050521201268900_CIT0017","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/ana.10639","article-title":"Increased Alzheimer pathology in Parkinson\u2019s disease related to antimuscarinic drugs","volume":"54","author":"Perry","year":"2003","journal-title":"Ann Neurol"},{"issue":"3","key":"2022050521201268900_CIT0018","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1001\/jamainternmed.2014.7663","article-title":"Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study","volume":"175","author":"Gray","year":"2015","journal-title":"JAMA Intern Med"},{"key":"2022050521201268900_CIT0019","volume-title":"The American Psychiatric Publishing Textbook of Substance Abuse Treatment","author":"Galanter","year":"2008"},{"key":"2022050521201268900_CIT0020","volume-title":"The Ashton Manual. Benzodiazepines: How They Work and How to Withdraw","author":"Ashton","year":"2002"},{"issue":"3","key":"2022050521201268900_CIT0021","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/pds.1360","article-title":"Application of lag-time into exposure definitions to control for protopathic bias","volume":"16","author":"Tamim","year":"2007","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2022050521201268900_CIT0022","author":"ZCTA."},{"issue":"10","key":"2022050521201268900_CIT0023","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1080\/14740338.2020.1811227","article-title":"Anticholinergic medications and risk of dementia in older adults: where are we now?","volume":"19","author":"Chatterjee","year":"2020","journal-title":"Expert Opin Drug Saf"},{"issue":"8","key":"2022050521201268900_CIT0024","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1001\/jamainternmed.2019.0677","article-title":"Anticholinergic drug exposure and the risk of dementia: a nested case\u2013control study","volume":"179","author":"Coupland","year":"2019","journal-title":"JAMA Intern Med"},{"issue":"6","key":"2022050521201268900_CIT0025","doi-asserted-by":"crossref","first-page":"467","DOI":"10.2165\/00002018-200225060-00012","article-title":"Causal association in pharmacovigilance and pharmacoepidemiology: thoughts on the application of the Austin Bradford-Hill criteria","volume":"25","author":"Shakir","year":"2002","journal-title":"Drug Saf"},{"key":"2022050521201268900_CIT0026","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3389\/fnbeh.2012.00024","article-title":"Cholinergic modulation of cognitive processing: insights drawn from computational models","volume":"6","author":"Newman","year":"2012","journal-title":"Front Behav Neurosci"},{"issue":"11","key":"2022050521201268900_CIT0027","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1586\/14737175.8.11.1703","article-title":"Cholinergic system during the progression of Alzheimer\u2019s disease: therapeutic implications","volume":"8","author":"Mufson","year":"2008","journal-title":"Expert Rev Neurother"},{"issue":"1","key":"2022050521201268900_CIT0028","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s12877-019-1280-2","article-title":"Anticholinergic and benzodiazepine medication use and risk of incident dementia: a UK cohort study","volume":"19","author":"Grossi","year":"2019","journal-title":"BMC Geriatr"},{"issue":"2","key":"2022050521201268900_CIT0029","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jamda.2019.05.010","article-title":"Association of benzodiazepine and anticholinergic drug usage with incident dementia: a prospective cohort study of community-dwelling older adults","volume":"21","author":"Hafdi","year":"2020","journal-title":"J Am Med Dir Assoc"}],"container-title":["The Journals of Gerontology: Series A"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/biomedgerontology\/advance-article-pdf\/doi\/10.1093\/gerona\/glab241\/40427904\/glab241.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/77\/5\/1035\/43552097\/glab241.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/77\/5\/1035\/43552097\/glab241.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T21:58:28Z","timestamp":1725659908000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article\/77\/5\/1035\/6354922"}},"subtitle":[],"editor":[{"given":"Lewis","family":"Lipsitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,8,19]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,8,19]]},"published-print":{"date-parts":[[2022,5,5]]}},"URL":"https:\/\/doi.org\/10.1093\/gerona\/glab241","relation":{},"ISSN":["1079-5006","1758-535X"],"issn-type":[{"value":"1079-5006","type":"print"},{"value":"1758-535X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,5,1]]},"published":{"date-parts":[[2021,8,19]]}}}