Association between Benzodiazepine Use and Dementia: A Meta-Analysis

PLoS One. 2015 May 27;10(5):e0127836. doi: 10.1371/journal.pone.0127836. eCollection 2015.


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.

Publication types

  • Meta-Analysis

MeSH terms

  • Aged
  • Aged, 80 and over
  • Benzodiazepines / administration & dosage*
  • Benzodiazepines / adverse effects*
  • Case-Control Studies
  • Dementia / chemically induced*
  • Dementia / etiology*
  • Dose-Response Relationship, Drug
  • Humans
  • Odds Ratio
  • Prospective Studies
  • Risk
  • Time Factors


  • Benzodiazepines

Grants and funding

These authors have no support or funding to report.