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Association of Benzodiazepine and Anticholinergic Drug Usage With Incident Dementia: A Prospective Cohort Study of Community-Dwelling Older Adults.
J Am Med Dir Assoc. 2020 02; 21(2):188-193.e3.JA

Abstract

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.

Authors+Show Affiliations

Department of Neurology, Amsterdam UMC/University of Amsterdam, Amsterdam, the Netherlands. Electronic address: m.hafdi@amc.uva.nl.Department of Neurology, Amsterdam UMC/University of Amsterdam, Amsterdam, the Netherlands.Department of General Practice, Amsterdam UMC/University of Amsterdam, Amsterdam, the Netherlands.Department of General Practice, Amsterdam UMC/University of Amsterdam, Amsterdam, the Netherlands.Department of Neurology, Amsterdam UMC/University of Amsterdam, Amsterdam, the Netherlands; Department of Neurology, Donders institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.Department of Neurology, Amsterdam UMC/University of Amsterdam, Amsterdam, the Netherlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31300339

Citation

Hafdi, Melanie, et al. "Association of Benzodiazepine and Anticholinergic Drug Usage With Incident Dementia: a Prospective Cohort Study of Community-Dwelling Older Adults." Journal of the American Medical Directors Association, vol. 21, no. 2, 2020, pp. 188-193.e3.
Hafdi M, Hoevenaar-Blom MP, Beishuizen CRL, et al. Association of Benzodiazepine and Anticholinergic Drug Usage With Incident Dementia: A Prospective Cohort Study of Community-Dwelling Older Adults. J Am Med Dir Assoc. 2020;21(2):188-193.e3.
Hafdi, M., Hoevenaar-Blom, M. P., Beishuizen, C. R. L., Moll van Charante, E. P., Richard, E., & van Gool, W. A. (2020). Association of Benzodiazepine and Anticholinergic Drug Usage With Incident Dementia: A Prospective Cohort Study of Community-Dwelling Older Adults. Journal of the American Medical Directors Association, 21(2), 188-e3. https://doi.org/10.1016/j.jamda.2019.05.010
Hafdi M, et al. Association of Benzodiazepine and Anticholinergic Drug Usage With Incident Dementia: a Prospective Cohort Study of Community-Dwelling Older Adults. J Am Med Dir Assoc. 2020;21(2):188-193.e3. PubMed PMID: 31300339.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Benzodiazepine and Anticholinergic Drug Usage With Incident Dementia: A Prospective Cohort Study of Community-Dwelling Older Adults. AU - Hafdi,Melanie, AU - Hoevenaar-Blom,Marieke P, AU - Beishuizen,Cathrien R L, AU - Moll van Charante,Eric P, AU - Richard,Edo, AU - van Gool,Willem A, Y1 - 2019/07/09/ PY - 2019/01/28/received PY - 2019/05/06/revised PY - 2019/05/11/accepted PY - 2019/7/14/pubmed PY - 2021/5/29/medline PY - 2019/7/14/entrez KW - Benzodiazepines KW - anticholinergic drugs KW - dementia KW - older adults SP - 188 EP - 193.e3 JF - Journal of the American Medical Directors Association JO - J Am Med Dir Assoc VL - 21 IS - 2 N2 - 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. SN - 1538-9375 UR - https://www.unboundmedicine.com/medline/citation/31300339/Association_of_Benzodiazepine_and_Anticholinergic_Drug_Usage_With_Incident_Dementia:_A_Prospective_Cohort_Study_of_Community_Dwelling_Older_Adults_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-8610(19)30428-1 DB - PRIME DP - Unbound Medicine ER -