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. 2020 Sep 17:11:00755.
doi: 10.3389/fpsyt.2020.00755. eCollection 2020.

The Effects of Benzodiazepine Use and Abuse on Cognition in the Elders: A Systematic Review and Meta-Analysis of Comparative Studies

Linzi Liu  1 , Linna Jia  1 , Peiying Jian  2 , Yifang Zhou  3 , Jian Zhou  1 , Feng Wu  1 , Yanqing Tang  1   3
Affiliations

The Effects of Benzodiazepine Use and Abuse on Cognition in the Elders: A Systematic Review and Meta-Analysis of Comparative Studies

Linzi Liu et al. Front Psychiatry. .

Abstract

Objective: Benzodiazepines (BZD) are one of the most frequently prescribed drugs worldwide. However, the cognitive effects of benzodiazepines in the elderly are highly debated. This systematic review and meta-analysis aims to explore the following two questions in the elderly population: (i) Do BZD lead to any impairments in cognitive functions in elderly users? and (ii) Which specific cognitive domains are most affected by BZD use and abuse?

Methods: First, we performed a literature search following the PRISMA guidelines. Electronic databases, including PubMed, PsycINFO, EMBASE, Cochrane Library, and Web of Science were searched until May 14th, 2020. After selecting the relevant articles, we integrated the results of the selected studies with a standardized cognitive classification method. Next, we performed meta-analyses with the random-effects model on the cognitive results. Finally, we specifically examined the cognitive impairments of BZD in the abuse subgroup.

Results: Of the included studies, eight of the thirteen had meta-analyzable data. Compared to the controls, elderly BZD users had significantly lower digital symbol test scores (n=253; SMD: -0.61, 95% CI: -0.91 to 0.31, I² = 0%, p < 0.0001). There was no significant difference in Mini-Mental State Examination, Auditory Verbal Learning Test, and Stroop Color and Word Test scores between BZD users and controls. According to the subgroup analyses, BZD abusers performed significantly worse than controls in Mini-Mental State Examination (n=7726; SMD: -0.23, 95% CI: -0.44 to -0.03, I² = 86%, p = 0.02), while there was no significant difference between the regular BZD users and the controls (n=1536; SMD: -0.05, 95% CI: -0.59 to 0.48, I² = 92%, p =0.85).

Conclusion: In the elderly population, the processing speed (digital symbol test scores) was significantly impaired in BZD users; global cognition (Mini-Mental State Examination scores) was significantly impaired in BZD abusers but not in BZD regular users. This study provides insight into the factors that interact with BZD cognitive effects, such as aging, testing tools, and abuse. Clinicians should be cautious when prescribing BZD for the elderly.

Systematic review registration: PROSPERO, identifier CRD42019124711.

Keywords: cognitive function; aged; benzodiazepines; cognitive dysfuction; meta-analysis; substance addiction.

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Figures

Figure 1
Figure 1
Flow diagram of the search and study identification process.
Figure 2
Figure 2
(A) Effect of BZD use on Mini Mental State Examination in the elderly: forest plot. (B) Effect of BZD use on Digital Symbol test in the elderly: forest plot. (C) Effect of BZD use on Auditory Verbal Learning Test in the elderly: forest plot. (D) Effect of BZD use on Stroop Color and Word Test in the elderly: forest plot.
Figure 3
Figure 3
Subgroup analysis of the effect of BZD abuse and regular use on mini mental state examination in the elderly.
See this image and copyright information in PMC

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