History of Benzodiazepine Prescriptions and Risk of Dementia: Possible Bias Due to Prevalent Users and Covariate Measurement Timing in a Nested Case-Control Study


Previous estimates of whether long-term exposure to benzodiazepines increases dementia risk are conflicting and are compromised by the difficulty of controlling for confounders and by reverse causation. We investigated how estimates for the association between benzodiazepine use and later dementia incidence varied based on study design choices, using a case-control study nested within the United Kingdom's Clinical Practice Research Datalink. A total of 40,770 dementia cases diagnosed between April 2006 and July 2015 were matched on age, sex, available data history, and deprivation to 283,933 control subjects. Benzodiazepines and Z-drug prescriptions were ascertained in a drug-exposure period 4-20 years before dementia diagnosis. Estimates varied with the inclusion of new or prevalent users, with the timing of covariate ascertainment, and with varying time between exposure and outcome. There was no association between any new prescription of benzodiazepines and dementia (adjusted odds ratio (OR) = 1.03, 95% confidence interval (CI): 1.00, 1.07), whereas an inverse association was observed among prevalent users (adjusted OR = 0.91, 95% CI: 0.87, 0.95), although this was likely induced by unintentional adjustment for colliders. By considering the choice of confounders and timing of exposure and covariate measurement, our findings overall are consistent with no causal effect of benzodiazepines or Z-drugs on dementia incidence.

Publication DOI: https://doi.org/10.1093/aje/kwz073
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: © The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journalpermissions@oup.com.
Uncontrolled Keywords: benzodiazepines,bias (epidemiology),case-control studies,dementia,risk,Epidemiology
Publication ISSN: 1476-6256
Last Modified: 20 May 2024 07:29
Date Deposited: 04 Apr 2019 12:48
Full Text Link:
Related URLs: https://academi ... /kwz073/5421030 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2019-07-01
Published Online Date: 2019-03-27
Accepted Date: 2019-03-14
Authors: Richardson, Kathryn
Mattishent, Katharina
Loke, Yoon K
Steel, Nicholas
Fox, Chris
Grossi, Carlota M
Bennett, Kathleen
Maidment, Ian (ORCID Profile 0000-0003-4152-9704)
Boustani, Malaz
Matthews, Fiona E
Myint, Phyo K
Campbell, Noll L
Brayne, Carol
Robinson, Louise
Savva, George


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