A Systematic Review of Published Systematic Reviews on Ginkgo Extract for Mild Cognitive Impairment and Dementia Reviewed: Zhang HF, Huang LB, Zhong YB, et al. An overview of systematic reviews of Ginkgo biloba extracts for mild cognitive impairment and dementia. Front Aging Neurosci. 2016;8:276. doi: 10.3389/fnagi.2016.00276. Participants Study Design Study Length Test Material Control Financial Disclosures Study Details: At a Glance 10 systematic reviews Systematic review of systematic reviews N/A Various ginkgo extracts Various None reported Current dementia and mild cognitive impairment (MCI) treatments address only symptoms; disease-modifying therapies for these conditions do not yet exist. Ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extract is used to treat symptoms of dementia, and many randomized, controlled trials have been conducted to evaluate efficacy and safety. Likewise, many systematic reviews have been conducted. The purpose of this study was to conduct a systematic review of the published ginkgo systematic reviews. Page 1 of 7
The following databases were searched from inception to September 2015 in both English and Chinese: Chinese Biological M edical Literature Database, Web of Science, PubMed, Chinese Wanfang Data, Chinese VIP Information, and Chinese National Knowledge Infrastructure. Included articles met the following criteria: (1) systematic reviews or meta-analyses; (2) used ginkgo extract for the prevention of cognitive function decline or for treating MCI, dementia, Alzheimer s disease (AD), vascular dementia (VD), or mixed dementia; and (3) used human subjects. Studies evaluating mixed treatments were excluded. The methodology of the systematic reviews was assessed with the Overview Quality Assessment Questionnaire (OQAQ). A total of 229 articles were located, and 10 reviews met the inclusion criteria. 1-10 The reviews were published from 2010 to 2015, nine were written in English, and one was written in Chinese. The studies included reviews of AD (n = 3); VD (n = 1); AD plus VD (n = 2); AD, VD, and mixed dementia (n = 3); and MCI (n = 1). Some of the included reviews also assessed ginkgo s effects on cognitive decline, dementia, and other variables. Each systematic review evaluated the methodology of the included studies, and it was determined that seven reviews included good-quality studies, two included moderate-quality studies, and one included poor studies. The OQAQ scores determined that nine of the systematic reviews had only minor or minimal flaws, and one was seriously flawed. Cognitive Decline Page 2 of 7
Two systematic reviews evaluated the ability of ginkgo extracts to prevent cognitive decline. 9,10 Both concluded that they had no significant preventative effect. However, one of the two reviews 9 included only two underpowered studies evaluating prevention, and the other 10 included a study with inconclusive findings. According to the authors, additional research is needed to determine the effect of ginkgo on prevention of cognitive decline. Mild Cognitive Impairment Only one systematic review evaluated MCI. 10 It concluded that there was no significant effect of ginkgo extract on activities of daily living (ADL). (However, the authors noted that There is no use measuring ADLs in patients with MCI or AAMI [age-associated memory impairment] who have subtle or no ADL impairment, and then saying there was no improvement. ) The review 10 also found that ginkgo alone and ginkgo plus conventional treatment had a significant effect on cognitive function compared with conventional therapy alone. Dementia In patients with dementia, two systematic reviews 1,6 concluded that 240 mg of EGb 761 ginkgo extract (Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany) was better than placebo on a global clinical assessment. Furthermore, one of the reviews 1 found a dose-dependent result: a 240-mg dose of EGb 761 produced better results than a 120-mg dose of EGb 761 on the global clinical assessment. Two additional systematic reviews 1,4 concluded that a 240-mg dose of EGb 761 was better than placebo at improving cognitive function. Four systematic reviews 1,4,5,7 concluded that a 240-mg dose of EGb 761 improved neuropsychiatric symptoms (NPS) and behavioral symptoms Page 3 of 7
compared with placebo in patients with dementia. Two of these reviews 4,5 reported significant improvements in ginkgo-treated patients with NPS, including depression, and one 7 reported significant improvements only in patients who showed behavioral symptoms; the fourth review 1 found that a 240-mg dose of EGb 761 was significantly superior to placebo in treating patients suffering from dementia with NPS, but did not include behavioral symptoms in its analysis. Two systematic reviews evaluated ADL in patients with dementia. One of these reviews 5 concluded an improvement in ADL and the other 7 which did not include several of the more recent and successful trials, according to the authors concluded no improvement. Alzheimer s Disease and Vascular Dementia In patients with AD, two systematic reviews 1,6 concluded that EGb 761 was better than placebo on a global clinical assessment, and another two 5,7 showed improvement in cognitive function. Two systematic reviews evaluated NPS in patients with AD; one 5 concluded an improvement in NPS and the other 7 concluded no improvement. Two systematic reviews evaluated quality of life (QoL) in patients with AD; one 10 concluded an improvement and the other 3 was inconclusive. (According to an expert peer reviewer of this article, this review included one study with potential methodological issues and failed to include another study 11 that found significant improvements in QoL.) Four systematic reviews 3,5,7,9 evaluated ADL in patients with AD and Page 4 of 7
concluded that ginkgo could improve ADL. One 9 found the effects on ADL were dose dependent and that a daily dose of 240 mg of ginkgo was more effective than placebo. In patients with VD, one systematic review 2 concluded that ginkgo was effective at improving ADL and cognitive function. Conclusion Eight systematic reviews evaluated safety. 1-5,7,8,10 All of the studies concluded that ginkgo had a similar frequency of adverse effects (AEs) or significantly fewer AEs compared with placebo. The authors state that to their knowledge this is the first systematic review of systematic reviews evaluating the efficacy and safety of ginkgo for the treatment of dementia and MCI. Overall, the authors conclude (1) there was a dose-dependent effect of ginkgo, with the higher dose (240 mg) being more effective; (2) patients taking ginkgo had fewer AEs than those taking placebo; (3) the effect of ginkgo on the progression of AD pathology has not been studied. A limitation of this article is that detailed analyses of optimal doses, durations, and treatments were not provided. Since this was a review of reviews, it is possible that the most recent randomized, controlled studies that could have potentially been included were not. There was no reported conflict of interest. Heather S. Oliff, PhD All photo credits: 2017 Steven Foster References 1. Gauthier S, Schlaefke S. Efficacy and tolerability of Ginkgo biloba extract Page 5 of 7
EGb 761R in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials. Clin Interv Aging. 2014;9:2065-2077. doi:10. 2147/CIA.S72728. 2. Hu Q, Tu X, Zhang Y, Yang WY, Long J. Systemic [sic] review of Ginkgo biloba extract for vascular dementia. Liaoning J Tradit Chin Med. 2013;4:683-686. 3. Janssen IM, Sturtz S, Skipka G, Zentner A, Velasco Garrido M, Busse R. Ginkgo biloba in Alzheimer s disease: a systematic review. Wien Med Wochenschr. 2010:160,539-546. doi:10.1007/s10354-010-0844-8. 4. Jiang L, Su L, Cui H, Ren J, Li C. Ginkgo biloba extract for dementia: a systematic review. Shanghai Arch Psychiatry. 2013;25:10-21. doi:10. 3969/j.issn.1002-0829.2013.01.005. 5. Tan MS, Yu JT, Tan CC, et al. Efficacy and adverse effects of Ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis. J Alzheimers Dis. 2015;43:589-603. doi:10.3233/jad- 140837. 6. Wang 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 effect meta-analysis. Pharmacopsychiatry. 2010;43:86-91. doi:10.1055/s-0029-1242817. 7. Weinmann S, Roll S, Schwarzbach C, Vauth C, Willich SN. Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC Geriatr. 2010;10:14. doi:10.1186/1471-2318-10-14. 8. Yang Z, Li WJ, Huang T, Chen JM, Zhang X. Meta-analysis of Ginkgo biloba extract for the treatment of Alzheimer s disease. Neural Regen Res. 2011;6:1125-1129.doi:10.3969/j.issn.1673-5374.2011.15.001. 9. Yang M, Xu DD, Zhang Y, Liu X, Hoeven R, Cho WC. A systematic review on natural medicines for the prevention and treatment of Alzheimer s disease with meta-analyses of intervention effect of ginkgo. Am J Chin Med. 2015;42:505-521.doi:10.1142/S0192415X14500335. Page 6 of 7
10. Yang G, Wang Y, Sun J, Zhang K, Liu J. Ginkgo biloba for mild cognitive impairment and Alzheimer s disease: a systematic review and metaanalysis of randomized controlled trials. Curr Top Med Chem. 2016;16:520-28. doi:10.2174/1568026615666150813143520. 11. Herrschaft H, Nacu A, Likhachev S, Sholomov I, Hoerr R, Schlaefke S. Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg. J Psychiatr Res. 2012 Jun;46(6):716-23. doi: 10.1016/j.jpsychires.2012.03.003. Page 7 of 7