The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Association of Benzodiazepine and Anticholinergic Drug Usage With Incident Dementia: A Prospective Cohort Study of Community-Dwelling Older Adults
Open accessAbstract
Objectives To examine the association of benzodiazepines and anticholinergic drug usage with the risk of dementia. Design Prospective cohort study. Setting Community-dwelling participants, recruited in family practices in the Netherlands. Participants In total, 3526 individuals aged 70 to 78 years without dementia within 116 participating family practices. Methods Information about drug use was reported at baseline and at 2-year follow-up and was cross-checked with the participants' electronic health records. Anticholinergic drug exposure was defined by the anticholinergic cognitive burden score. Participants were evaluated for dementia during follow-up assessments every 2 years, supplemented by information from electronic health records and the National Death Registry. Results During a median follow-up of 6.7 years, dementia developed in 233 participants (7%). In participants using benzodiazepines, 6% developed dementia vs 7% in nonusers [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-1.07]. Persistent usage of benzodiazepines at baseline and after 2-year follow-up did not substantially alter the point-estimate (HR 0.60, 95% CI 0.34-1.10). Use of any anticholinergic drugs was not associated with incident dementia (HR 1.01, 95% CI 0.50-1.10). Dementia risk was significantly increased for participants with persistent drug use with a high anticholinergic cognitive burden score (HR 1.95, 95% CI 1.13-3.38) though this effect was absent when excluding participants taking antidepressants or antipsychotics (HR 0.42, 95% CI 0.06-3.01). Conclusions and implications In our study population, benzodiazepine usage was not associated with an increased risk of dementia. Persistent high anticholinergic exposure was associated with an increased risk of dementia over 6 years of follow-up, and this association was driven by antidepressant or antipsychotic drug use, suggesting confounding by indication bias contributing to this. Although this observation could ameliorate prescription hesitance, healthcare providers are still advised to carefully weigh the potential benefits of benzodiazepines and anticholinergic drugs against the associated adverse health outcomes.
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Other studies did link antidepressant use to increased dementia risk.
“In contrast, other studies did link antidepressant use to increased dementia risk. 4,8-14”
From Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy (2024) · cites this paper as [10]
The indexed Abstract reports an association between persistent high anticholinergic exposure and increased dementia risk, driven by antidepressant or antipsychotic use. It does not establish a separate association for antidepressant use alone, and it suggests confounding by indication may contribute to the observed association. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPrior cohort studies on antidepressant use and dementia risk have produced contrasting results.
“Long-term observational data are needed, but cohort studies to date have produced contrasting results. While various studies observed increased risk of dementia in antidepressant users, 4,8-14 several others did not. 15-19”
From Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy (2024) · cites this paper as [10]
The indexed passage (Abstract; page unavailable) reports this cohort’s findings on anticholinergic exposure and dementia risk, including the role of antidepressant or antipsychotic use. It does not discuss whether prior cohort studies of antidepressant use produced contrasting results. Searches for that comparison and for increased dementia risk in antidepressant users found no supporting passage in our copy. (LLM, conf=0.74)
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Cites
Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study
Gray, S. L., Anderson, M. L., Dublin, S., Hanlon, J. T., Hubbard, R., Walker, R., Yu, O., Crane, P. K., & Larson, E. B. (2015) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2014.7663 · Cited by 1,111
Anticholinergic drugs and risk of dementia: case-control study
Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., Myint, P. K., Grossi, C. M., Mattishent, K., Bennett, K., et al. (2018) · BMJ · doi:10.1136/bmj.k1315 · Cited by 520
Risk Factors for Vascular Dementia and Alzheimer Disease
Gorelick, P. B. (2004) · Stroke · doi:10.1161/01.str.0000143318.70292.47 · Cited by 365
Gray, S. L., Dublin, S., Yu, O., Walker, R., Anderson, M., Hubbard, R. A., Crane, P. K., & Larson, E. B. (2016) · BMJ · doi:10.1136/bmj.i90 · Cited by 233
Bali, V., Chatterjee, S., Carnahan, R. M., Chen, H., Johnson, M. L., & Aparasu, R. R. (2015) · Psychiatric Services · doi:10.1176/appi.ps.201500011 · Cited by 23
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Research works printed but not linked: 21
- Mura, 2013, Chronic use of benzodiazepines and latent cognitive decline in the elderly: Results from the Three-city study, Eur Neuropsychopharmacol, 23, 212, 10.1016/j.euroneuro.2012.05.004 · DOI
- Verdoux, 2005, Is benzodiazepine use a risk factor for cognitive decline and dementia? A literature review of epidemiological studies, Psychol Med, 35, 307, 10.1017/S0033291704003897 · DOI
- Fox, 2011, Anticholinergic medication use and cognitive impairment in the older population: The medical research council cognitive function and ageing study, J Am Geriatr Soc, 59, 1477, 10.1111/j.1532-5415.2011.03491.x · DOI · Paper page
- Zhong, 2015, Association between benzodiazepine use and dementia: A meta-analysis, PLoS One, 10, e0127836, 10.1371/journal.pone.0127836 · DOI
- Carrière, 2009, Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population, Arch Intern Med, 169, 1317, 10.1001/archinternmed.2009.229 · DOI · Paper page
- Campbell, 2009, The cognitive impact of anticholinergics: A clinical review, Clin Interv Aging, 4, 225
- Wu, 2009, The association between dementia and long-term use of benzodiazepine in the elderly: Nested case-control study using claims data, Am J Geriatr Psychiatry, 17, 614, 10.1097/JGP.0b013e3181a65210 · DOI
- Linden, 2004, Prevalence and appropriateness of psychotropic drug use in old age: Results from the Berlin Aging Study (BASE), Int Psychogeriatr, 16, 461, 10.1017/S1041610204000420 · DOI
- Jessen, 2010, Anticholinergic drug use and risk for dementia: Target for dementia prevention, Eur Arch Psychiatry Clin Neurosci, 260, S111, 10.1007/s00406-010-0156-4 · DOI · Paper page
- Ancelin, 2006, Nondegenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: Longitudinal cohort study, BMJ, 332, 455, 10.1136/bmj.38740.439664.DE · DOI · Paper page
- Moll van Charante, 2016, Effectiveness of a 6-year multidomain vascular care intervention to prevent dementia (preDIVA): A cluster-randomised controlled trial, Lancet, 388, 797, 10.1016/S0140-6736(16)30950-3 · DOI · Paper page
- McKhann, 1984, Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease, Neurology, 34, 939, 10.1212/WNL.34.7.939 · DOI · Paper page
- Neary, 1998, Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria, Neurology, 51, 1546, 10.1212/WNL.51.6.1546 · DOI · Paper page
- McKeith, 2006, Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): Report of the Consortium on DLB International Workshop, J Alzheimers Dis, 9, 417, 10.3233/JAD-2006-9S347 · DOI
- McKeith, 1996, Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): Report of the consortium on DLB international workshop, Neurology, 47, 1113, 10.1212/WNL.47.5.1113 · DOI · Paper page
- Roman, 1993, Vascular dementia: Diagnostic criteria for research studies: Report of the NINDS-AIREN International Workshop, Neurology, 43, 250, 10.1212/WNL.43.2.250 · DOI · Paper page
- Boustani, 2008, Impact of anticholinergics on the aging brain: A review and practical application, Aging Health, 4, 311, 10.2217/1745509X.4.3.311 · DOI · Paper page
- Imfeld, 2015, Benzodiazepine use and risk of developing Alzheimer's disease or vascular dementia: A case-control analysis, Drug Safety, 38, 909, 10.1007/s40264-015-0319-3 · DOI
- Billioti de Gage, 2012, Benzodiazepine use and risk of dementia: Prospective population based study, BMJ, 345, e6231, 10.1136/bmj.e6231 · DOI · Paper page
- Billioti de Gage, 2014, Benzodiazepine use and risk of Alzheimer's disease: Case-control study, BMJ, 349, g5205, 10.1136/bmj.g5205 · DOI
- Ligthart, 2012, Cardiovascular risk management in community-dwelling elderly: Opportunities for prevention, Eur J Prev Cardiol, 19, 1365, 10.1177/1741826711422979 · DOI
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Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy
vom Hofe, I., Stricker, B. H., Vernooij, M. W., Ikram, M. K., Ikram, M. A., & Wolters, F. J. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13807 · Cited by 24
Metadata
- Authors
- Hafdi, M., Hoevenaar-Blom, M. P., Beishuizen, C. R. L., Moll van Charante, E. P., Richard, E., & van Gool, W. A.
- Affiliations
- Amsterdam University Medical Centers (NL)
- Radboud University Nijmegen (NL)
- Corresponding author
- Hafdi, Melanie
- Venue
- Journal of the American Medical Directors Association
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 21
- Issue
- 2
- Pages
- 188-193.e3
- ISSN
- 1525-8610 (ISSN-L)
- OpenAlex
- W2958868025
- Cited by
- 37
- References
- 5
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 2 · 2021: 7 · 2020: 6
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- Journal of the American Medical Directors Association (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Ministerie van Volksgezondheid, Welzijn en Sport (50-50110-98-020)
- ZonMw (62000015)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Keywords
- benzodiazepines, anticholinergic agents, dementia risk, antidepressants, antipsychotic drugs, confounding by indication, older adults, community-dwelling older adults, polypharmacy, family medicine patients, electronic health records, anticholinergic burden
- MeSH terms
- Aged, Benzodiazepines, Dementia, Humans, Netherlands, Prospective Studies, Cholinergic Antagonists, Independent Living
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