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 14 th , 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

Background: Benzodiazepines (BZD) are common medications for sedative, hypnotic, and anxiolytic that are especially prevalent in older adults. Previous studies have shown that BZD use could impair users' cognition, significantly affecting their quality of life. Past research has shown that higher education might play a protective role in the process of cognitive decline. Very few studies had examined the cognitive effects of BZD on highly educated older adults. The study aimed to explore how cognitive functions would be affected by benzodiazepines among highly educated older adults. Method: 140 older adults with an average education period of 14.8 years were included in this study. The subjects were divided into three separate groups, the long-term BZD users (≥180 days), short-term BZD users (<180 days), and non-users. Demographics and cognitive assessments for the three groups were analyzed using the analysis of variance (ANOVA), the chi-squared test, and the analysis of covariance (ANCOVA). To examine the association between BZD use and cognition a multiple linear aggression approach was used. Result: All three groups were significantly different from each other when looking at executive functioning in the Trail Making Test B (TMT-B). Compared to the control group, short-term BZD users showed significant defects in TMT-B time (p = 0.002) and TMT-B errors (p < 0.001); long-term BZD users showed significant defect on TMT-B time (p = 0.041). Compared to short-term BZD users, long-term BZD users showed significant merit on TMT-B errors (p = 0.001). No significant differences were found in other cognitive tasks that reflected general cognition, verbal memory, language fluency, and visual memory. After adjusting for demographic, increased BZD use over time was positively associated with scores for the revised Brief Visuospatial Memory Test (r = 0.377, p = 0.012). Conclusion: BZD use may be significantly associated with worse executive functioning in highly educated older adults. However, there is no association between the duration of BZD use and increased cognitive deficits in highly educated older adults. This study Liu et al. Benzodiazepine Use and Cognition Decline identified future experimental directions including potential longitudinal studies, within-subject studies comparing mood disorder patients' cognitive performance before and after onset of BZD use, and between-subject studies that directly compare BZD's effect on subjects with the same baseline of cognitive functioning.

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