Gingko for Preventing Alzheimer's? Forget It

Abstract & Commentary

By Norman R. Relkin, MD, PhD, Director, Memory Disorders Program; Associate Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Relkin reports that he receives grant/research support from Baxter Bioscience, and is a consultant to Eisai, Pfizer, Myriad, and Smart Genetics.

Synopsis: Gingko biloba does not prevent Alzheimer's disease.

Source: Dekosky S, Williamson JD, Fitzpatrick AL,et al. Ginkgo biloba for prevention of dementia: A randomized controlled trial. JAMA 2008;300:2253-2262.

Taking gingko biloba extract does not prevent the development of dementia, according to a federally funded, prospective clinical trial involving more than 3,000 subjects. The U.S. multicenter Ginkgo Evaluation of Memory (GEM) trial recruited 3,069 community-dwelling volunteers age 75 years or older who were either cognitively normal or in a state of mild cognitive impairment at baseline. The subjects were randomly assigned to receive either 120 mg of gingko biloba extract EGb 761 (Schwabe Pharmaceuticals) or an identical-appearing placebo twice a day. Participants received follow-up evaluations that included cognitive testing every 6 months for a median of 6.1 years.

There was a low overall drop-out rate from the study (6.3%) and no difference in discontinuations or side effects between the gingko-treated and placebo groups. A total of 523 subjects developed dementia over the course of the study — in most cases (92%), Alzheimer's disease (AD). There was no significant difference in the incidence of AD or other dementias among patients who took gingko (3.3 per 100 person years) versus those who took placebo (2.9 per 100 person years). There was no observed benefit associated with EGb 761, whether subjects tested normal initially or had mild cognitive impairment at baseline.

In an exploratory analysis, individuals taking gingko extract who had pre-existing cerebrovascular disease had a 56% increased risk of AD relative to patients given placebo. However, the authors caution that the study was not powered to examine interactions with cerebrovascular disease, and as such, that particular finding should not be considered conclusive.

In all, no evidence was found to support the use of gingko biloba extract EGb 761 for the prevention of dementia in individuals age 75 or older.

Comments

Gingko biloba extract is a natural herbal derivative that has been purported to act as a memory enhancer and/or dementia preventative. The GEM study is the largest prospective trial to date of gingko biloba extract for dementia prevention, and its results are unequivocally negative. The study employed a well-characterized gingko biloba preparation (EGb 761) that contains known amounts of flavonoids and terpene lactones, substances that preclinical studies suggested might be beneficial in combating AD and other forms of dementia. While it could be argued that another preparation might still prove beneficial, EGb 761 is one of the few standardized formulations available. In addition, EGb 761 was used in previous studies that suggested gingko biloba has beneficial effects on memory loss.

The GEM study involved a large number of subjects, had excellent retention, and employed a sufficiently lengthy follow-up period to adequately test ginkgo's effects on dementia incidence. The selection of patients older than 75 years of age was a necessary expedient to obtain an adequate number of incident dementia cases. If longer use or younger populations are needed to observe benefits, it's unlikely that there will be sufficient enthusiasm to carry out such a study after the negative outcome of the GEM trial. Another large study (GuidAge) of EGb 761 for prevention of AD is currently being completed in France. The GuidAge study is also a placebo-controlled study of EGB 761 at a slightly higher dose (240 mg twice a day) in elderly subjects (mean age approximately 77) with initial memory complaints.

This initial GEM study report focuses on EGb761's effects on dementia incidence and does not further describe the cognitive outcomes. It is unlikely, but still possible, that gingko exerts beneficial effects on memory without affecting overall dementia incidence. Additional reports from the GEM and GuidAge studies can be anticipated that should clarify this issue. Based on the currently available findings, however, physicians should not recommend gingko biloba for dementia prevention.