Ginkgo and Alzheimer's Disease

Townsend Letter for Doctors and Patients,  Jan, 2001  by Kerry Bone

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Two recently published studies would seem to suggest that Ginkgo biloba standardized extract (GBE), using evidence-based criteria is now the treatment of choice for early stages of Alzheimer's disease (AD). The first paper compared the efficacy of four cholinesterase inhibitors (tacrine, donepezil, rivastigmine and metrifonate) and GBE in Alzheimer's disease. [1] The differences in the effects of the active substance and placebo on cognition were measured on the ADAS-Cog scale, taking into account the different degrees of dementia in the various studies and the dropout rate due to adverse drug reactions. Efficacy, expressed as the delay in symptom progression or the difference in response rate between active substance and placebo, showed no major differences between the four cholinesterase inhibitors and GBE. Only tacrine exhibited a high dropout rate due to adverse drug reactions. The author concluded that second-generation cholinesterase inhibitors (donepezil, rivastigmine, metrifonate) and GBE should be co nsidered equally effective in the treatment of mild to moderate Alzheimer's dementia.

The second study examined the assumption in Alzheimer's disease that the loss of cortical cholinergic function found in postmortem brain specimens is also a feature of much earlier disease. [2] The results were that only patients with severe dementia showed reduced cholinergic activity and that cholinergic deficits were not apparent in individuals with mild AD. The authors suggested that patients with more severe disease should be the target for cholinesterase inhibitor drugs. The corollary is that GBE, since it is not a cholinesterase inhibitor, is probably more suited to patients with early AD.

Commentary

The comparison of GBE with cholinesterase inhibitor drugs was based on two GBE and AD trials published in 1996 and 1997. Since then, other investigations have appeared in the literature. A late 1997 study in a small group of patients concluded that 240 mg per day of GBE over three months was effective in mild to moderate AD. [3] The US research team who published their landmark study in JAMA conducted a fresh analysis of 26 weeks of treatment with 120 mg GBE (using their previous data) to provide a realistic image of the efficacy that could be expected over this period of time. [4] They wrote: "In comparison to the baseline values, the placebo group showed a statistically significant worsening in all domains of assessment, while the group receiving EGb (GBE) was considered slightly improved on the cognitive assessment and the daily living and social behavior."

An open, uncontrolled trial was conducted to determine whether GBE or tacrine had noticeable pharmacological effects on elderly subjects diagnosed with possible or probable AD. [5] Data from 18 participants with an average age of 67.4 years were analyzed. Each subject was randomly administered 40 mg tacrine or 240 mg GBE in two separate sessions. EEG analysis indicated that both GBE, and to a lesser extent tacrine, exhibited pharmacological effects consistent with them being "cognition activators."

The scientific world is now showing a great interest in GBE. Last year it was announced that the United States National Institutes of Health (NIH) has awarded funding for a multicenter study on GBE and dementia. [6] The University of Pittsburgh School of Medicine was awarded a six year cooperative agreement (an assistance mechanism in which the NIH will have substantial involvement with the recipient during the performance of the planned activity) totalling US$15 million to co-ordinate a multicenter effort to study the effectiveness of GBE in preventing dementia in older individuals. Steven T. DeKosky, MD, Professor of Psychiatry, Neurology and Neurobiology, and Director of the Alzheimer's Disease Research Center at the University of Pittsburgh School of Medicine will serve as the principal investigator of this study. Data collection and analysis of the four study sites will be coordinated by the University of Washington, Seattle, Washington.

The six-year study will enroll a total of 2,000 participants, who will be randomly assigned to one of two groups. Study participants will take 240 mg. GBE and will be compared to a second group of individuals on placebo. The primary outcome of this study will be the onset of any type of dementia. The secondary outcome will be measured by changes in cognitive function.

References

(1.) Wettstein A. Cholinesterase inhibitors and Ginkgo extracts - are they comparable in the treatment of dementia? Phytomedicine 2000; 6(6): 393-401

(2.) Davis KL, Mohs RC, Mann D et al. Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA 1999; 281(15): 1401-1406

(3.) Maurer K, Ihl R, Dierks T et al. Clinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type. J Psychiatr Res 1997; 31(6): 645-655

(4.) Le Bars PL, Kieser M, Itil KZ. A 26-week analysis of a double-blind, placebo-controlled trial of the Ginkgo biloba extract EGb 761((R)) in dementia. Dement Geriatr Cogn Disord 2000; 11(4): 230-237