Association between Benzodiazepine Use and Dementia: A Meta-Analysis

Abstract

Background: The association between long-term benzodiazepine use and risk of dementia remains controversial. Therefore, current study aimed to quantify this association, and to explore a potential dose-response pattern.

Methods: We searched PubMed, Embase and the Cochrane Library through August 17, 2014. We included nested case-control or prospective cohort studies that provided risk estimates on the association of benzodiazepine use with risk of dementia, and a clear definition of status of benzodiazepine use. Overall effect size was calculated using a random-effects model.

Findings: Six studies were eligible for inclusion, involving 11,891 dementia cases and 45,391 participants. Compared with never users, pooled adjusted risk ratios (RRs) for dementia were 1.49 (95% confidence interval (CI) 1.30-1.72) for ever users, 1.55 (95% CI 1.31-1.83) for recent users, and 1.55 (95% CI 1.17-2.03) for past users. The risk of dementia increased by 22% for every additional 20 defined daily dose per year (RR, 1.22, 95%CI 1.18-1.25). When we restricted our meta-analyses to unadjusted RRs, all initial significant associations persisted.

Conclusions: Long-term benzodiazepine users have an increased risk of dementia compared with never users. However, findings from our study should be treated with caution due to limited studies and potential reverse causation. Large prospective cohort studies with long follow-up duration are warranted to confirm these findings.

Fig 1. The flowchart of identifying relevant studies.

Fig 2. Meta-analysis on ever use of benzodiazepines and risk of dementia.

The squares represent the risk estimate for each individual study, with the area reflecting the weight assigned to the study. The horizontal line across each square represents the 95% confidence interval. The diamond represents the summary risk estimate, with width representing 95% confidence interval.

Fig 3. Meta-analysis on recent use of benzodiazepines and risk of dementia.

The squares represent the risk estimate for each individual study, with the area reflecting the weight assigned to the study. The horizontal line across each square represents the 95% confidence interval. The diamond represents the summary risk estimate, with width representing 95% confidence interval.

Fig 4. Meta-analysis on past use of benzodiazepines and risk of dementia.

The squares represent the risk estimate for each individual study, with the area reflecting the weight assigned to the study. The horizontal line across each square represents the 95% confidence interval. The diamond represents the summary risk estimate, with width representing 95% confidence interval.

Fig 5. Sensitivity analysis: exclusion of a single study in turn.

The study being cited on the left is the one being left out in each analysis. The circle represents the summary risk estimates after exclusion of a single study, and the corresponding dot line represents 95% confidence interval. The middle vertical solid line represents summary risk estimates of all included studies, and left and right vertical solid line represent lower limit and upper limit, respectively. Panel A, ever use versus never use; Panel B, recent use versus never use; Panel C, past use versus never use.