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

Naseri, Amirreza; Sadigh-Eteghad, Saeed; Seyedi-Sahebari, Sepideh; Hosseini, Mohammad-Salar; Hajebrahimi, Sakineh; Salehi-Pourmehr, Hanieh

doi:10.1590/1980-5764-DN-2022-0053

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Dementia & Neuropsychologia

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View & Review • Dement. neuropsychol. 17 • 2023 • https://doi.org/10.1590/1980-5764-DN-2022-0053 copy

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

Efeitos cognitivos de drogas anticolinérgicas individuais: uma revisão sistemática e meta-análise

Authorship SCIMAGO INSTITUTIONS RANKINGS

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.

Keywords:
Cholinergic Antagonists; Cognition; Memory; Attention; Executive Function; Systematic Review; Meta-Analysis

Outcome	Number of studies	Heterogeneity		Meta-analysis model	Standard difference in means	Standard error	95% confidence intervals		p-value
Outcome	Number of studies	I² (%)	p-value	Meta-analysis model	Standard difference in means	Standard error	Lower limit	Upper limit	p-value
Attention	12	81.69	<0.01^* * Note: Statistically significant.	Random effect	−0.85	0.26	−1.38	−0.33	<0.01^* * Note: Statistically significant.
Delayed recall	16	73.27	<0.01^* * Note: Statistically significant.	Random effect	−1.54	0.22	−1.97	−1.10	<0.01^* * Note: Statistically significant.
Digit span	6	72.80	<0.01^* * Note: Statistically significant.	Random effect	−0.65	0.28	−1.21	−0.10	0.02^* * Note: Statistically significant.
Free recall	7	53.53	0.04^* * Note: Statistically significant.	Random effect	−1.18	0.23	−1.63	−0.73	<0.01^* * Note: Statistically significant.
Immediate recall	11	65.85	<0.01^* * Note: Statistically significant.	Random effect	−1.82	0.26	−2.35	−1.30	<0.01^* * Note: Statistically significant.
Matching to sample	7	86.99	<0.01^* * Note: Statistically significant.	Random effect	−1.76	0.41	−2.57	−0.96	<0.01^* * Note: Statistically significant.
Cognitive function	14	84.59	<0.01^* * Note: Statistically significant.	Random effect	−0.95	0.26	−1.46	−0.44	<0.01^* * Note: Statistically significant.
Complex memory tasks	18	80.57	<0.01^* * Note: Statistically significant.	Random effect	−1.31	0.24	−1.78	−0.84	<0.01^* * Note: Statistically significant.
Recognition	13	84.17	<0.01^* * Note: Statistically significant.	Random effect	−1.84	0.32	−2.48	−1.21	<0.01^* * Note: Statistically significant.

Academia Brasileira de Neurologia, Departamento de Neurologia Cognitiva e Envelhecimento R. Vergueiro, 1353 sl.1404 - Ed. Top Towers Offices, Torre Norte, São Paulo, SP, Brazil, CEP 04101-000, Tel.: +55 11 5084-9463 | +55 11 5083-3876 - São Paulo - SP - Brazil
E-mail: revistadementia@abneuro.org.br | demneuropsy@uol.com.br

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[1] Correspondence: Hanieh Salehi-Pourmehr; Email: Poormehrh@yahoo.com.