Synopsis: Especially for Alzheimer’s patients who cannot tolerate the cholinesterase inhibitors, and who are not depressed, ginkgo may be a useful agent.
Source: Le Bars PL, et al. JAMA 1997;278:1327-1332.
EGb 761 is a particular extract of ginkgo biloba used in Europe to alleviate symptoms associated with numerous cognitive disorders. Its use in dementia is based on positive results from a few controlled clinical trials, most of which did not include standard assessments of cognition and behavior. To assess the efficacy and safety of EGb in Alzheimer’s disease and multi-infarct dementia, Le Bars and colleagues conducted a 52-week, randomized, double-blind, placebo-controlled, parallel-group multicenter study of mildly to severely demented outpatients without other significant medical conditions. Patients were randomly assigned to treatment with EGb (120 mg/d) or placebo. Safety, compliance, and drug dispensation were monitored every three months, with complete outcome evaluation at 12, 26, and 52 weeks.
From 309 patients included in an intent-to-treat analysis, 202 provided evaluable data for the 52-week end point analysis. The EGb group had an Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score 1.4 points better than the placebo group (P = 0.04) and a Geriatric Evaluation by Relative’s Rating Instrument (GERRI) score 0.14 points better than the placebo group (P = 0.004). The same patterns were observed with the evaluable data set in which 27% of patients treated with EGb achieved at least a four-point improvement on the ADAS-Cog, compared with 14% taking placebo (P = 0.005); on the GERRI, 37% were considered improved with EGb, compared with 23% taking placebo (P = 0.003). No difference was seen in the Clinical Global Impression of Change scale. There were no significant differences in adverse events (incidence or severity) between the EGb and placebo groups.
EGb was safe and appears capable of stabilizing and, in a substantial number of cases, improving the cognitive performance and the social functioning of demented patients for six months to a year. Although modest, the changes induced by EGb were objectively measured by the ADAS-Cog and were of sufficient magnitude to be recognized by the caregivers.
COMMENT BY JOHN LA PUMA, MD
Alzheimer’s causes two-thirds of all dementia and affects approximately 4 million Americans. Age and family history are the primary risk factors; nearly 30% of the population age 85 or older has the disease. The goals of treatment are to improve quality of life, to enhance cognition, mood, and behavior, and to improve functional performance. People with Alzheimer’s live an average of about a decade after diagnosis.
Ginkgo biloba is a tree, the dried leaves of which are extracted to form a botanical approved in Germany for treatment of dementia, and widely prescribed for circulatory disorders there. In fact, it is the most widely prescribed medicine in Germany.
In this well-designed randomized controlled trial sponsored by Dr. Willmar Schwabe Pharmaceuticals, investigators used ginkgo biloba extract consisting of 24% flavone glycosides and 6% terpenelactones to treat clinical manifestations of dementia, including cognitive decline. Most patients had mild Alzheimer’s disease. Though drop-out rates were highonly 167 completed the one-year trialand the dose was modestthe investigators note that 240 mg daily may have greater effectthere was improvement on two of the three standardized cognitive and behavioral scales, especially for the Alzheimer’s group. There were no significant differences in the number of adverse events for EGb and placebo, though gastrointestinal signs and symptoms occurred 18 times in the EGb group and only nine times in the placebo group. A possible mechanism of action for ginkgo was postulated by the authors to be the antioxidant effects of "membrane protection and neurotransmission modulation" but was not defined further.
All medications should be used cautiously in the elderly, who are especially susceptible to polypharmacy. Even so, this is the first double-blind, randomized, controlled trial of its kind for ginkgo for dementia, and, given the promising results, more will likely follow. Especially for Alzheimer’s patients who cannot tolerate the cholin-esterase inhibitors, and who are not depressed, ginkgo may be a useful agent. Standardized cognitive and behavioral scales, with regular patient surveillance every 3-6 months, will be helpful in assessing ginkgo’s effect and patients’ progress. (Dr. La Puma is Principal Investigator, The Cooking, Health, Eating, and Fitness (CHOP) Solution, Alexian Brothers Medical Center, Elk Grove, IL.)
The primary risk factors for Alzheimer’s disease include:
a. age.
b. diet.
c. family history.
d. both a and c.
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