Background: Benzodiazepines are a widely used medication in developed countries, particularly among elderly patients. However, benzodiazepines are known to affect memory and cognition and might thus enhance the risk of dementia. The objective of this review is to synthesize evidence from observational studies that evaluated the association between benzodiazepines use and dementia risk.

Summary: We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risk of benzodiazepines use on dementia outcome. All control observational studies that compared dementia outcome in patients with benzodiazepine use with a control group were included. We calculated pooled ORs using a random-effects model. Ten studies (of 3,696 studies identified) were included in the systematic review, of which 8 studies were included in random-effects meta-analysis and sensitivity analyses. Odds of dementia were 78% higher in those who used benzodiazepines compared with those who did not use benzodiazepines (OR 1.78; 95% CI 1.33-2.38). In subgroup analysis, the higher association was still found in the studies from Asia (OR 2.40; 95% CI 1.66-3.47) whereas a moderate association was observed in the studies from North America and Europe (OR 1.49; 95% CI 1.34-1.65 and OR 1.43; 95% CI 1.16-1.75). Also, diabetics, hypertension, cardiac disease, and statin drugs were associated with increased risk of dementia but negative association was observed in the case of body mass index. There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the sensitivity analyses. There was significant statistical and clinical heterogeneity among the studies for the main analysis and most of the sensitivity analyses. Key Messages: Our results suggest that benzodiazepine use is significantly associated with dementia risk. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or the result of some unmeasured confounding variable. Therefore, more research is needed.