Systematic Review of Ginkgo Finds Potential Treatment for Dementia

Dementia encompasses a wide range of symptoms associated with a decline in memory and loss of the ability to perform everyday activities in elderly populations. Alzheimer’s disease (AD) and vascular dementia (VD) make up the vast majority of dementia cases. Ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extract (GbE) has become one of the most widely used herbal remedies for dementia. Thus, many clinical trials have already examined the effects of GbE on dementia, and many systematic reviews (SRs) have analyzed these trials. This study sought to provide a comprehensive assessment of the effectiveness of GbE in the treatment of dementia based on the evidence provided in the SRs.

All SRs which evaluated the efficacy and effectiveness of GbE as treatment (not prevention) of patients with diagnosed dementia, AD and/or VD, or mild cognitive impairment (MCI) were included. SRs were eligible only if they included the use of statistical methods (i.e., meta-analysis) to analyze randomized controlled trial (RCT) data. SRs were included whether GbE was administered alone or in combination with drugs. There were no limitations on dosage, and GbE could be administered orally or intravenously. PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects (DARE), and Google Scholar were searched from inception to June 2016.

In total, 59 RCTs were reviewed, with patients ranging from those with any form of dementia, dementia with behavioral and psychological symptoms, cognitive impairment, or AD. Twelve SRs met the inclusion criteria; all included only RCTs (of which most were placebo-controlled trials). The included SRs were published between 2009 and 2016, and they were performed in China, Germany, Japan, and the United Kingdom. The standardized extract EGb 761® (Dr Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany) was used in many RCTs, with six SRs including only RCTs that used EGb 761. Intervention duration varied from two to 52 weeks, and dosing varied from 60 mg/day to 600 mg/day.

Outcomes of interest varied but included one or more of the following: cognitive performance, activities of daily living (ADLs), clinical global impression, quality of life (QOL), and safety. With the exception of three SRs1-3 all remaining SRs showed the statistically significant effectiveness of GbE on cognitive performance in people with dementia. Eight SRs evaluated the effect of GbE on ADLs, and, apart from one SR,3 seven SRs showed a statistically significant effect of GbE on ADLs in people with dementia. Five SRs evaluated the effect of GbE on clinical global impression of dementia, of which three showed a statistically significant effect of GbE. Of the five SRs that evaluated QOL, two concluded there was no significant difference in QOL, two did not pool the QOL data, and only one SR pooling data from two RCTs suggested a beneficial effect of GbE on QOL. Eight SRs evaluated the safety of GbE, and none found any significant difference in adverse events or side effects compared to placebo.

Seven SRs included RCTs in which GbE was administered for at least 22 weeks, and the data reported in these SRs consistently favored the beneficial effects of GbE. The five SRs in which GbE was administered for less than 22 weeks reported data that were “quite inconsistent.” This study found no particular evidence suggesting a beneficial effect of GbE on cognitive performance, ADLs, or clinical global impression when GbE was administered for less than 22 weeks. In addition, few SRs showed a beneficial effect of GbE at a dose less than 200 mg/day. In fact, four SRs consistently showed a beneficial effect of GbE on cognitive performance at a dose greater than 200 mg/day (usually 240 mg/day). Few SRs indicated a beneficial effect of GbE on ADLs and clinical global impression at a dose less than 200 mg/day.

The quality of SRs was evaluated using the AMSTAR (Assessment of Multiple Systematic Reviews) tool, and overall, the majority of reviews were found to be of good or acceptable quality. However, many of the reviewed RCTs in these SRs were of poor quality and had a high risk of bias, meaning the overall quality of evidence reviewed was low to moderate. That being said, based on the evidence gathered that met inclusion criteria, this overview found GbE to have beneficial effects over placebo on cognitive performance, ADLs, and clinical global impression when administered at a dose greater than 200 mg/day for 22 weeks or more. Globally, over 46 million people were living with dementia in 2015, and this number is expected to reach 131.5 million by 2050.4 With no cure or prevention yet found, future research is warranted. In order to better assess GbE efficacy as a treatment for dementia, future studies should take the beneficial dosing and intervention length found by this overview into account.

References

1Yang Z, Li W, Huang T, Chen J, Zhang X. Meta-analysis of Ginkgo biloba extract for the treatment of Alzheimer’s disease. Neural Regen Res. 2011;6(15):1125-1129.

2Wang BS, Wang H, Song YY, et al. Effectiveness of standardized Ginkgo biloba extract on cognitive symptoms of dementia with a six-month treatment: a bivariate random effects meta-analysis. Pharmacopsychiatry. 2010;43(3):86-91. doi: 10.1055/s-0029-1242817.

3Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. January 21, 2009;(1):CD003120. doi: 10.1002/14651858.CD003120.pub3.

4Dementia statistics. Alzheimer’s Disease International website. Available at: https://www.alz.co.uk/research/statistics. Accessed September 11, 2017.

Yuan Q, Wang CW, Shi J, Lin ZX. Effects of Ginkgo biloba on dementia: An overview of systematic reviews. J Ethnopharmacol. January 2017;195:1-9.

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