EGb in the Treatment for Patients with VCI: A Systematic Review and Meta-Analysis

Abstract

Background. Ginkgo biloba extract (EGb) is widely used to treat impairments in memory, cognition, activities of daily living, inflammation, edema, stroke, Alzheimer’s dementia, and aging. Aim. We aimed to evaluate the safety and efficacy of EGb in treating vascular cognitive impairment (VCI). Methods. The systematic review was performed using the latest guidelines. We searched for EGb-related trials up to March 1, 2021, in four Chinese databases, three English databases, and clinical trial registry platforms. Randomized controlled trials (RCTs) were included if the study enrolled participants with VCI. Two reviewers independently extracted the data and critically appraised the study quality. Heterogeneity was quantified with $I^2$ . Both sensitivity and subgroup analyses were used to identify the sources of heterogeneity. Publication bias was assessed with funnel plots. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to rate the evidence quality. Outcomes included assessments using the Activities of Daily Living (ADL), Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Hasegawa Dementia Scale (HDS), Barthel Index (BI), Functional Activity Questionnaire (FAQ), and adverse events. Results. In this study, a total of 2019 patients in 23 RCTs were included. EGb appeared to be more effective than control conditions as assessed by the results of cognitive function evaluation, including MMSE ( $\text{M}{\text{D}}_{\text{MMSE},\text{EGb}\text{vs}.\text{blank}}=3.04$ , 95% CI: 0.10-5.98; $\text{M}{\text{D}}_{\text{MMSE},\text{EGb}\text{vs}.\text{drugs}\text{for}\text{VCI}}=2.70$ , 95% CI: 1.39-4.01; $\text{M}{\text{D}}_{\text{MMSE},\text{EGb}+\text{drugs}\text{for}\text{VCI}\text{vs}.\text{blank}}=5.90$ , 95% CI: 4.21-7.59; and $\text{M}{\text{D}}_{\text{MMSE},\text{EGb}+\text{drugs}\text{for}\text{VCI}\text{vs}.\text{drugs}\text{for}\text{VCI}}=3.14$ , 95% CI: 2.14-4.15), MoCA ( $\text{M}{\text{D}}_{\text{MoCA},\text{EGb}\text{vs}.\text{blank}}=5.30$ , 95% CI: 2.15-8.46; $\text{M}{\text{D}}_{\text{MoCA},\text{EGb}+\text{drugs}\text{for}\text{VCI}\text{vs}.\text{blank}}=2.66$ , 95% CI: 1.82-3.50; and $\text{M}{\text{D}}_{\text{MoCA},\text{EGb}+\text{drugs}\text{for}\text{VCI}\text{vs}.\text{drugs}\text{for}\text{VCI}}=2.56$ , 95% CI: 1.85-3.27), HDS ( $\text{M}{\text{D}}_{\text{HDS},\text{EGb}\text{vs}.\text{blank}}=6.50$ ; 95% CI: 4.86-8.14; $\text{M}{\text{D}}_{\text{HDS},\text{EGb}+\text{drugs}\text{for}\text{VCI}\text{vs}.\text{drugs}\text{for}\text{VCI}}=3.60$ , 95% CI: 2.50-4.70), ADL ( $\text{M}{\text{D}}_{\text{ADL},\text{EGb}\text{vs}.\text{blank}}=7.20$ , 95% CI: 3.28-11.12; $\text{M}{\text{D}}_{\text{ADL},\text{EGb}+\text{drugs}\text{for}\text{VCI}\text{vs}.\text{blank}}=10.00$ , 95% CI: 7.51-12.49; and $\text{M}{\text{D}}_{\text{ADL},\text{EGb}+\text{drugs}\text{for}\text{VCI}\text{vs}.\text{drugs}\text{for}\text{VCI}}=9.20$ , 95% CI: 7.26-11.14), BI ( $\text{M}{\text{D}}_{\text{BI},\text{EGb}+\text{drugs}\text{for}\text{VCI}\text{vs}.\text{drugs}\text{for}\text{VCI}}=5.71$ , 95% CI: 2.99-8.43; $\text{M}{\text{D}}_{\text{FAQ},\text{EGb}\text{vs}.\text{drugs}\text{for}\text{VCI}}=-1.43$ , 95% CI: -2.78 to 0.08), and FAQ ( $\text{M}{\text{D}}_{\text{FAQ},\text{EGb}+\text{drugs}\text{for}\text{VCI}\text{vs}.\text{drugs}\text{for}\text{VCI}}=-2.17$ , 95% CI: -4.13 to 0.21). Evidence of certainty ranged from medium certainty to very low certainty. Conclusion. This meta-analysis showed that EGb may be an effective and safe treatment in improving MMSE, MOCA, ADL, and BI for VCI patients within three months of diagnosis. However, given the quality of the included RCTs, more preregistered trials are needed that explicitly examine the efficacy of EGb. This systematic review has been registered on PROSPERO, with the registration number CRD42021232967.