What's That Herb Again ... ? Ginkgo for Dementia

Abstract & Commentary

By Russell H. Greenfield, MD, Editor

Synopsis: A well-regarded, standardized extract of Ginkgo biloba does not appear to help prevent development of dementia in seniors with baseline normal or mildly impaired cognitive function. Whether use of ginkgo earlier in life has a primary preventive effect on development of dementia remains to be determined.

Source: DeKosky ST, et al. Ginkgo biloba for prevention of dementia: A randomized controlled trial. JAMA 2008;300:2253-2262.

The authors of this multicenter, randomized, double-blind trial (The Ginkgo Evaluation of Memory study) sought to determine whether use of a standardized extract of Ginkgo biloba over time would decrease the incidence of all-cause dementia, especially Alzheimer's disease, in people older than age 75 years. Participants (n = 3,069 total, n = 482 of whom with mild cognitive impairment; mean age of all subjects = 79.1 years) had to have either normal cognitive function or mild cognitive impairment at baseline. Subjects were randomized to receive either 120 mg Ginkgo biloba extract (EGb-761) or an identical placebo tablet twice daily. They were then assessed every six months for incident dementia using multiple tests and scales, and employing DSM-IV criteria. If a diagnosis of dementia were being considered, additional neurologic work-up was undertaken, including MRI scanning, to exclude atypical etiologies of dementia.

After a median follow-up of 6.1 years, a total of 523 people developed dementia, with 92% of them being classified as having Alzheimer's disease or Alzheimer's disease with concomitant vascular disease. Overall dementia rates were 3.3/100 years in the active group and 2.9/100 years in the placebo group. The hazard ratio (HR) for ginkgo use and all-cause dementia was 1.12, and 1.16 for Alzheimer's disease compared with placebo. Adverse events were similar in both groups, and rates of major bleeding did not differ statistically, but there were twice as many hemorrhagic strokes in the ginkgo group than in the placebo group (16 vs 8); however, the numbers were very small. The authors conclude that a standardized extract of Ginkgo biloba given in a commonly used dose does not reduce the overall incidence of dementia in seniors with normal cognitive function or those with mild cognitive impairment.

Commentary

This is a very well-done trial using a well-standardized extract of Ginkgo biloba (EGb-761) and employing comprehensive assessments of cognitive status to support or refute a diagnosis of dementia in senior citizens. The methodology is sound even though compliance was only about 60% by trial's end. The sample size is significant, follow-up was superb, and lots were tested individually and identified. EGb-761 has been well studied and is considered by most experts the standard by which other ginkgo extracts must be measured. The problem comes in how to interpret the data in the context of younger patients who might be at risk for dementia.

Since the study only addressed individuals older than age 75 we do not know, as the authors rightly point out, whether a longer duration of ginkgo administration started earlier in life would have offered a primary preventive effect. Thus, the results seem clear only in that older individuals should not use ginkgo to try to stave off dementia. As for those of us still in our prime, whether that's true or just in our minds (cognitively, of course), the question of ginkgo's potential utility remains to be answered.

Truly effective treatments to prevent or delay the onset of dementia, and to preserve cognitive function, have yet to be identified. The current study contributes to our understanding in a select population but not to younger people, where preventive strategies may be most effective.