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

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ObjectiveBipolar disorder (BD) has a higher lifetime rate of suicide attempts (SA) than other psychiatric disorders. Furthermore, BD patients with SA (BD + S) are prone to a worse quality of life. However, the pathophysiology of BD + S is poorly understood. To further reveal the potential mechanisms of BD + S, abnormalities in peripheral plasma inflammatory cytokines and brain white matter (WM) in BD + S, as well as the correlation between them are investigated.MethodsWe tested the levels of TNF-α, IL-1β, and IL-6 in peripheral plasma and collected the diffusion tensor imaging (DTI) data from 14 BD + S, 24 BD patients without SA (BD-S), and 26 healthy controls (HCs). The three groups were matched by age and gender. The levels of TNF-α, IL-1β, and IL-6 were detected by Luminex multifactor detection technology, and the fractional anisotropy (FA) values were employed to depict the alterations of WM. Partial correlation analyses were conducted to detect correlations between levels of TNF-α, IL-1β, and IL-6 and changes of WM, and the relationships between severity of clinical symptoms, including scores of HAMD-17 and YMRS, and cytokine levels or FA values in all groups.ResultsFor plasma inflammatory cytokines, there was no significant difference in their levels except for IL-6 among the three groups. Post-hoc analyses revealed that increased IL-6 level was only detected in BD + S (p &lt; 0.05, Bonferroni correction). For DTI, BD + S showed specifically decreased FA in the bilateral middle cerebellar peduncle and the left superior corona radiata compared to BD-S and HCs (p &lt; 0.05, Bonferroni correction). Additionally, both BD + S and BD-S groups revealed decreased FA in the bilateral body and genu of corpus callosum (CC) compared to HCs (p &lt; 0.05, Bonferroni correction). No significant correlation between plasma inflammatory cytokines and WM integrity was found. In the BD + S group, we found negative correlation between the scores of YMRS and FA values of the left middle cerebellar peduncle (r = −0.74, p = 0.035).ConclusionThe inflammation and impaired WM integrity may provide a scientific basis to understand the potential mechanisms of BD + S.