Gingko biloba extract is widely used in the United States and Europe. Four mechanisms of action are thought to account for some of the positive effects that have been described: a vasoregulatory action, a cognition-enhancing action, a stress-alleviating action and, possibly, a gene-regulatory action. Results of one widely cited study showed some cognitive improvement in patients with Alzheimer's disease or vascular dementias. This study, by van Dongen and colleagues, was designed to determine the efficacy, dose-dependence and durability of ginkgo biloba special extract EGb 761 (hereafter called ginkgo) in older patients with mild-to-moderate dementia or age-associated memory impairment.
Patients with dementia (including those with Alzheimer's, vascular dementia or a mixed type of dementia) and nondementia patients with age-associated memory impairment were included in the study. All patients were at least 50 years of age and did not have severe depression. To address the goals of this trial, a two-stage randomization strategy was implemented. After a three-week placebo run-in period (during which no placebo response was allowed if the patient was to continue), patients were randomized to receive either placebo, 160 mg of gingko (two 80-mg tablets) or 240 mg of gingko (two 120-mg tablets) twice daily. After the first 12-week treatment period, patients taking ginkgo were randomized again (to assess durability) to receive either placebo or gingko for another 12 weeks. Those taking placebo continued taking placebo. Various psychometric, psychopathologic and behavioral functions were tested.
There were 256 patients in the initial three-week placebo run-in segment; of these, 63 demented patients and 151 nondemented patients (but with substantial cognitive decline) were randomized to the study. No marked differences in baseline characteristics were evident between the groups. After 24 weeks of treatment, the only differences noted were in the self-assessed activities of daily living; however, these changes were also noted at 12 weeks. This effect was not impressive and disappeared after adjusting for confounding variables.
The authors conclude that there is no clinically relevant or sustained effect of gingko in patients with mild-to-moderate dementia or age-associated memory impairment. The authors acknowledge that their trial did not reproduce the benefits of ginkgo therapy in older patients with dementia or age-associated memory impairment that were demonstrated in previous trials. Although there were some differences in study design and conduct between trials, they do not believe the differences to be great enough to account for the different results. They further state that the results of their study do not “fully neutralize the positive effects of previous studies.”
editor's note: Although patients and their families are eager to embrace any possible treatment for Alzheimer's disease, the results of this study provide some evidence that previous reports of gingko biloba's effects on cognitive impairment may be overstated. The authors do note, however, that further studies are needed. Unfortunately, this study did not address the presence of adverse effects, or the issues of unregulated gingko or impurities in its formulation. Results from the previous, more positive studies will certainly continue to be cited by those searching for a definitive treatment for persons with this devastating disease.—g.b.h.