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.
Study Details: At a GlanceParticipants
| 10 systematic reviews | Study Design
| Systematic review of systematic reviews | Study Length
| N/A | Test Material
| Various ginkgo extracts | Control
| Various | Financial Disclosures
| 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.
The following databases were searched from inception to September 2015 in both
English and Chinese: Chinese Biological Medical 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
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 reviews9 included only two
underpowered studies evaluating prevention, and the other10 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 review10 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 reviews1,6 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 reviews1
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 reviews1,4 concluded that a 240-mg dose of EGb 761 was
better than placebo at improving cognitive function.
Four
systematic reviews1,4,5,7 concluded that a 240-mg dose of EGb 761
improved neuropsychiatric symptoms (NPS) and behavioral symptoms compared with
placebo in patients with dementia. Two of these reviews4,5 reported
significant improvements in ginkgo-treated patients with NPS, including
depression, and one7 reported significant improvements only in patients
who showed behavioral symptoms; the fourth review1 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
reviews5 concluded an improvement in ADL and the other7 —
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 reviews1,6 concluded that EGb 761
was better than placebo on a global clinical assessment, and another two5,7
showed improvement in cognitive function.
Two
systematic reviews evaluated NPS in patients with AD; one5 concluded
an improvement in NPS and the other7 concluded no improvement.
Two
systematic reviews evaluated quality of life (QoL) in patients with AD; one10
concluded an improvement and the other3 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 study11
that found significant improvements in QoL.)
Four
systematic reviews3,5,7,9 evaluated ADL in patients with AD and
concluded that ginkgo could improve ADL. One9 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 review2 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
- Gauthier
S, Schlaefke S. Efficacy and tolerability of Ginkgo biloba extract 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Yang G, Wang Y, Sun J, Zhang K, Liu J. Ginkgo
biloba for mild cognitive impairment and Alzheimer’s disease: a systematic review
and meta-analysis of randomized controlled trials. Curr Top Med Chem. 2016;16:520-28. doi:10.2174/1568026615666150813143520.
- 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.
|