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.
| Original language | English |
|---|---|
| Pages (from-to) | 1031-1039 |
| Number of pages | 9 |
| Journal | Journal of Alzheimer's Disease |
| Volume | 69 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 01-01-2019 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Clinical Psychology
- Geriatrics and Gerontology
- Psychiatry and Mental health
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Efficacy and safety of glycogen synthase kinase 3 inhibitors for Alzheimer's disease : A systematic review and meta-analysis. / Matsunaga, Shinji; Fujishiro, Hiroshige; Takechi, Hajime.
In: Journal of Alzheimer's Disease, Vol. 69, No. 4, 01.01.2019, p. 1031-1039.Research output: Contribution to journal › Review article
TY - JOUR
T1 - Efficacy and safety of glycogen synthase kinase 3 inhibitors for Alzheimer's disease
T2 - A systematic review and meta-analysis
AU - Matsunaga, Shinji
AU - Fujishiro, Hiroshige
AU - Takechi, Hajime
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
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U2 - 10.3233/JAD-190256
DO - 10.3233/JAD-190256
M3 - Review article
VL - 69
SP - 1031
EP - 1039
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 4
ER -