Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis

Abstract

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.

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“…A recent meta‐analysis of 10 studies showed that the risk of developing dementia following long‐term BZD usage is 78% higher than for non‐BZDs users (Islam et al . ). Furthermore, a 9‐year longitudinal study linked long‐term use of diazepam with impairments in cognitive performance in elderly subjects (Bierman et al .…”

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“…and H.-C.Y.) who are experts in drug and disease relationship research [13,[15][16][17][18]. The relevant electronic databases (e.g., PubMed, EMBASE, and Scopus) were searched for articles published between January 1, 1990 and November 1, 2017, which reported the possible association between psoriasis and MS risk.…”

“…When the number of studies is not large, the visual interpretation and test for asymmetry of the funnel plot of the publications are not very reliable [15]. Figure 3 shows the funnel plot that indicates the existence of some publication bias.…”

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“…In contrast, in their case control studies, Imfeld et al (2015) showed that BZD use was not associated with an increased risk of AD or vascular dementia. Three meta-analyses (Islam et al, 2016;Penninkilampi & Eslick, 2018;Zhong, Wang, Zhang, & Zhao, 2015) suggested that BZD use was significantly associated with an increased risk of dementia, and a dose-response association was highlighted by Zhong et al (2015). Furthermore, the final meta-analysis performed by Penninkilampi and Eslick (2018) only included studies that controlled for protopathic bias.…”