Expert Consensus on EGb 761 for Dementia and Mild Cognitive Impairment

The prevalence of mild cognitive impairment (MCI) and dementia is increasing globally as people live longer. Vascular dementia (VaD) and Alzheimer’s disease (AD) are the most common forms of dementia, and cerebrovascular disease (CVD) is often concomitant with AD (AD + CVD). The goal of treatment is to stabilize or slow disease progression, reduce behavioral and psychological symptoms of dementia (BPSD), improve quality of life, and reduce caregiver burden. In Asia, the first-line therapies for dementia are acetylcholinesterase inhibitors (AChEIs), N‐methyl‐D‐aspartate (NMDA) receptor antagonists (e.g., memantine) are second-line therapies, and the proprietary ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extract EGb761 (Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany) is also used. In China, the Philippines, Thailand, and Vietnam, EGb 761 is classified as a drug; in Malaysia and Singapore, it is regulated as a supplement; and in Indonesia, it is classified as a “phytopharmaceutical.” To help guide clinical practice in the Asia region and improve the care of patients with dementia and MCI, the Asian Clinical Expert Group on Neurocognitive Disorders (ACEND) was convened in 2017 to critically review the literature on EGb 761 in the treatment of AD, VaD, and BPSD, and develop consensus statements on the role of EGb 761 in the treatment of dementia. In this article, the clinical evidence is briefly summarized and the evidence-based consensus recommendations of the ACEND are reported.

The ACEND group consisted of twenty Asian specialists (neurologists, geriatricians, psychiatrists, and a pharmacist) and an expert advisory member from Germany. Prior to the consensus meeting, group members were provided with all relevant English language publications on the use of EGb761 in dementia and MCI for critical review. The literature included four meta-analyses published between 2014 and 2018 and nine multicenter, randomized, controlled trials (RCTs) published between 1996 and 2014. The RCTs enrolled a total of 2862 patients with AD, VaD, MCI, mostly with BPSD; evaluated 120 to 240 mg/day EGb 761 for 12 to 52 weeks, and all were double-blind, placebo-controlled trials except for one MCI study in which the controls received only general health care. On the day of the consensus meeting, the group identified salient issues relating to the use of EGb 761 in clinical practice and developed consensus on a series of evidence-based recommendations “unrelated to different regulatory classifications in respective countries.”

The consensus statements were classified using the following criteria: Class I: Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective (is recommended/is indicated); Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy (is reasonable to consider); Class IIb: Usefulness/efficacy is less well established by evidence/opinion (may be reasonable to consider); and Class III: Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful (is not recommended).

The level of evidence supporting each consensus statement was rated using the following criteria: Level A: Data derived from multiple randomized, placebo‐controlled clinical trials, or meta‐analyses; Level B: Data derived from a single randomized clinical trial or large nonrandomized studies; and Level C: Consensus of opinion of experts and/or case reports, small studies, retrospective studies.

ACEND Evidence-based Consensus Recommendations

1a. Based on the available evidence for EGb 761 specifically (Class I, Level A evidence), the ACEND members consider current best practice for pharmacological treatment to be as follows:

  • AD: AChEIs, memantine, and EGb 761.
  • VaD: AChEIs, memantine, EGb 761, and antiplatelet therapy.
  • BPSD: AChEIs, nonpharmacological treatment, antipsychotics (off‐label), memantine, selective serotonin reuptake inhibitors, sedatives, and EGb761.

1b. EGb 761 may be considered for use in patients with MCI (Class IIb, Level A evidence).

1c. EGb 761 can be used as a single agent was deemed appropriate in certain individuals. It is important to allow sufficient time for the effects of EGb 761 to become evident (Class I, Level A evidence). EGb 761 can be used as an add‐on agent, in combination with standard anti-dementia drugs (Class IIb, Level A evidence).

1d. Given the clinical data available to date, 240 mg/day EGb 761 is an evidence‐based treatment option for the management of AD, VaD, and AD + CVD. Evidence suggests that 240 mg/day EGb 761 has efficacy comparable with AChEIs and memantine in the treatment of dementia, including improvements in cognition, BPSD, and daily function in patients with VaD and AD + CVD (Class IIa, Level A evidence).

1e. The use of EGb 761 for the treatment of AD, VaD, and AD + CVD is particularly warranted when patients are unable to tolerate the side effects of AChEIs or memantine, or there is a lack of efficacy with standard treatments (Expert Recommendation).

  1. Key management options adjunctive to standard pharmacological therapy for AD, VaD, and BPSD include psychosocial interventions, cognitive behavioral therapy, vitamin B, folic acid, and EGb 761 (Class IIa; Level A evidence).
  2. Concomitant management of co‐morbidities, such as hypertension, in patients with AD, VaD, and BPSD is highly important (Expert Recommendation).
  3. EGb761 does not appear to prevent dementia and cannot currently be recommended for the prevention of dementia (Class III; Level A evidence).
  4. Current safety evidence suggests a good tolerability profile with EGb761 in the treatment of MCI, AD, VaD, and BPSD (Level A evidence).
  5. Based on existing data in AD, VaD, and AD + CVD, there appears to be no overall added risk of bleeding with EGb761 (Level A evidence). Further studies are required in certain patient subgroups, including those with a high cerebral microbleed load (> four microbleeds) in the cortical areas. In such cases, patients should be warned of a possible increased risk of bleeding (Expert Recommendation).
  6. No significant interaction of EGb761 with concomitant anticoagulant (Level B evidence) or antiplatelet (Level A evidence) agents has been demonstrated.
  7. EGb761 may be considered for incorporation into national clinical practice guidelines as part of the treatment algorithm for AD, VaD, and BPSD (Class IIa, Level A evidence).

In summary, the members of the ACEND “foresee an important role for EGb 761, used alone or as add-on therapy, in the treatment of MCI and dementia, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists.” While EGb761 has not been shown to prevent progression to dementia, there is robust evidence that the efficacy of EGb 761 240 mg/d is comparable to AChEIs and memantine in terms of improvement in cognition, behavior, and ability to maintain activities of daily living in patients with AD and VaD. EGb 761 does not appear to increase the overall risk of bleeding, and there is no evidence of interaction with antiplatelet drugs and anticoagulants in young, healthy volunteers; however, it is unclear how accurately these data may be extrapolated to elderly patient populations with multiple co-morbidities. The authors conclude “the evidence indicates that EGb 761® has a favorable therapeutic index, and it is anticipated that the data and recommendations discussed herein may encourage consideration for the incorporation of EGb 761® into various national guidelines around Asia, to further enhance the symptomatic care of individuals with AD and VaD.”


Kandiah N, Ong PA, Yuda T, et al. Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease: Expert consensus on the use of Ginkgo biloba extract, EGb 761®CNS Neurosci Ther. February 2019;25(2):288-298. doi: 10.1111/cns.13095.