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Review of Ginkgo for Cognitive Function and Alzheimer’s Disease

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Reviewed: Liu H, Ye M, Guo H. An updated review of randomized clinical trials testing the improvement of cognitive function of Ginkgo biloba extract in healthy people and Alzheimer’s patients. Front Pharmacol. 2020;10:1688. doi: 10.3389/fphar.2019.01688.

Clinical studies have evaluated the effects of ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extract (GLE) on cognition since at least the 1980s. The purpose of this review was to summarize data from large-scale studies that assessed the effects of GLE on cognitive outcomes in healthy people and those with Alzheimer’s disease (AD). PubMed, ScienceDirect, Europe PMC, and SpringerLink databases were searched from inception through 2019 for large-scale human clinical trials of GLE for cognitive function. No other details on the search methodology were provided.

‘Negative’ Studies

Eleven studies, published from 1984 through 2005, were classified by the reviewers as having negative results. However, most of these studies showed some positive and some negative results, and some found no significant differences.

Five of the 11 studies evaluated a single (acute) dose of GLE in healthy participants. The acute studies evaluated 112 participants who received GLE dosages ranging from 120 mg to 600 mg. The chronic studies evaluated 968 participants who received 80-240 mg GLE/day for two to 26 weeks. Most studies included healthy participants. Some trials did not specify a primary outcome variable that could render a study outcome positive or negative. In such trials, it is typical that some of the hypothesized effects are confirmed, and others are not. In addition, studies in which no significant difference was found were called negative, when it would be more correct to say the study “failed to find a difference.” This could be for many reasons, including improper study designs, inadequate statistical power (e.g., due to small study populations), quality control issues, etc., in addition to being truly without effect.

‘Positive’ Studies

The review included 17 articles, published from 1987 through 2019, with positive results. It appears that some research teams published more than one paper using the same study population. Fourteen papers described randomized and placebo-controlled studies.

A single dose of GLE was evaluated in one study. The acute study assessed 120 mg, 240 mg, and 360 mg GLE in 20 healthy students and reported significant improvements in speed of attention, quality of memory, and speed of memory. Another study evaluated 120 mg, 150 mg, 240 mg, and 300 mg GLE for two days in healthy participants and reported a significant improvement in short-term memory and reaction time.

Four studies evaluated 437 patients with cognitive impairment who were treated with placebo or 120 mg GLE/day for eight to 26 weeks. These studies reported significant improvements on various cognitive assessments, including the Kendrick Battery, digit recall task, Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), and Geriatric Evaluation by Relative’s Rating Instrument.

Fifty-one patients with mild cognitive impairment were assessed in one study and were treated with placebo or 160 mg GLE/day for 24 weeks. This study reported significant improvement on the Syndrom-Kurztest (SKT) and Clinical Global Impression (CGI) scale.

Nine studies evaluated 2,529 patients with cognitive impairment who were treated with placebo or 240 mg GLE/day for 12 to 24 weeks. These studies reported significant improvements on SKT, CGI, ADAS-cog, the Neuropsychiatric Inventory (NPI), activities-of-daily-living subscale of the Gottfries-Bråne-Steen (GBS-ADL) scale, Hamilton Depression Rating (HAM-D) scale, and Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) scale. Patients with dementia due to AD (N = 190) were evaluated in another study and were treated with 5 or 10 mg donepezil/day or 240 mg GLE/day for 12 months. The study reported no significant differences between treatment groups on the Mini-Mental State Exam (MMSE).

Study Limitations

There were several overall differences between the negative and positive studies. Compared with the positive studies, the negative studies generally had a shorter duration, used a smaller dose of GLE, were conducted in healthy rather than impaired participants, and included younger participants.

The review authors concluded that “ginkgo may be able to improve the cognitive function in patients suffering from mild dementia [after] administration [for] more than 24 weeks [using an] appropriate dosage (240 mg per day).” However, they acknowledge that AD is a chronic disease with a long progressive duration, and no study evaluated GLE supplementation for longer than one year.

A limitation of this review is that the search criteria were not defined and reported. Also, the authors claim that they searched for large-scale studies, but many studies had less than 30 participants. Another limitation is that the specific GLE products were not reported.