Cognitive effects of individual anticholinergic drugs: a systematic review and meta-analysis

Abstract

Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial findings. Objective: The objective of this study was to investigate the effects of individual ACs on different aspects of cognitive function based on clinical trial studies. Methods: This systematic review was conducted following the PRISMA statement. A systematic search was performed in Embase, PubMed, Cochrane Library, Scopus, and Web of Science databases. Risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists and the meta-analysis was performed using the CMA software. Results: Out of 3,026 results of searching, 138 studies were included. A total of 38 studies that assess the cognitive impacts of scopolamine were included in the meta-analysis. Included studies reported cognitive effects of scopolamine, mecamylamine, atropine, biperiden, oxybutynin, trihexyphenidyl, benzhexol, and dicyclomine; however, glycopyrrolate, trospium, tolterodine, darifenacin, fesoterodine, tiotropium, and ipratropium were not associated with cognitive decline. Based on the meta-analyses, scopolamine was associated with reduced recognition (SDM-1.84; 95%CI-2.48 to-1.21; p<0.01), immediate recall (SDM-1.82; 95%CI-2.35 to-1.30; p<0.01), matching to sample (SDM-1.76; 95%CI-2.57 to-0.96; p<0.01), delayed recall (SDM-1.54; 95%CI-1.97 to-1.10; p<0.01), complex memory tasks (SDM-1.31; 95%CI-1.78 to-0.84; p<0.01), free recall (SDM-1.18; 95%CI-1.63 to-0.73; p<0.01), cognitive function (SDM-0.95; 95%CI-1.46 to-0.44; p<0.01), attention (SDM-0.85; 95%CI-1.38 to-0.33; p<0.01), and digit span (SDM-0.65; 95%CI-1.21 to-0.10; p=0.02). There was a high RoB in our included study, especially in terms of dealing with possible cofounders. Conclusion: The limitations of this study suggest a need for more well-designed studies with a longer duration of follow-up on this topic to reach more reliable evidence.