Affiliations: [a] Department of Geriatrics and Cognitive Disorders, Fujita Health University School of Medicine, Kutsukake, Toyoake, Aichi, Japan
| [b] Department of Psychiatry, Kawasaki Memorial Hospital, Miyamae, Kawasaki, Kanagawa, Japan
Correspondence:
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Correspondence to: Shinji Matsunaga, MD, PhD, Department of Geriatrics and Cognitive Disorders, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. Tel.: +81 562 93 9083; Fax: +81 562 93 9021; E-mail: shinjim@fujita-hu.ac.jp.
Abstract: Background:The efficacy and safety of glycogen synthase kinase 3 (GSK-3) inhibitors in patients with Alzheimer’s disease (AD) is unknown. Objective:A systematic review and meta-analysis of randomized controlled trials (RCTs) to test GSK-3 inhibitors on AD patients. Methods:We included RCTs of GSK-3 inhibitors in AD patients and subjects with mild cognitive impairment (MCI), using cognitive function scores as a primary measure. Results:Five RCTs (three RCTs using lithium and two RCTs using tideglusib) with 568 patients were included. There was no significant difference in cognitive function scores between the GSK-3 inhibitors and placebo groups [standardized mean difference (SMD) = –0.25, p = 0.11, I2 = 55% ]. However, significant heterogeneity remained. A sensitivity analysis revealed that the lithium subgroup was more effective on cognitive function scores than placebo for AD and MCI (lithium subgroup: SMD = –0.41, p = 0.04; tideglusib subgroup: SMD = –0.02, p = 0.89). Moreover, a meta-regression analysis showed that the effect size of GSK-3 inhibitors on cognitive function scores was associated with study duration (coefficient, –0.0116). For safety outcomes, tideglusib was associated with a higher incidence of increased aspartate aminotransferase than placebo. There were no significant differences in other secondary outcomes between treatments. Conclusion:Our results suggested that GSK-3 inhibitors were ineffective in treating AD and MCI; however, several studies included in the present meta-analysis were small, and future studies using a larger sample size are needed.
