Uncertain Association Between Benzodiazepine Use and the Risk of Dementia: A Cohort Study

Abstract

Objective: To examine the association between benzodiazepine use and the risk of dementia.

Design, setting, and participants: We conducted a retrospective cohort study, using a nationwide healthcare database of South Korea (2002-2016). The participants included new users of benzodiazepines aged ≥50 years, with no prior prescription record of benzodiazepines or a history of dementia within the previous 5 years (2002-2006).

Methods: Outcome was defined as an incident dementia with specified algorithms using diagnosis and prescription records, with the application of a 5-year lag-time following the index date during which outcomes were censored. We used a multivariable Cox proportional hazard model to estimate hazard ratio (HR) and the 95% confidence interval (CI). Comorbidities and comedications were treated as time-varying covariates in 90-day windows, and an active comparator was used to reduce potential bias from confounding by indication. Active comparators were defined as new-users of antidepressants.

Results: Our final participants included 616,256 patients, after propensity score estimation and matching on a 1:1 ratio. We observed a 23% increase in the risk of dementia in benzodiazepine users, compared with that in nonusers, over a mean follow-up period of 5.5 years (HR 1.23, 95% CI 1.14-1.32). A consistent finding was observed when the lag-time duration was extended to 7 years, revealing a close to null association (HR 1.17, 95% CI 1.04-1.30). When new-users of antidepressants were used as the active comparator, no increase in the risk of dementia with benzodiazepines was observed over 7 years (HR 1.01, 95% CI 0.81-1.27).

Conclusions and implications: A significant association was observed between benzodiazepine use and the risk of dementia, compared with nonusers. However, a null or negative association was observed with the use of the active comparator, suggesting the absence of a causal association between dementia and benzodiazepine use.

Keywords: Dementia; benzodiazepine; cohort studies; propensity score.