Practice parameter: Management of dementia (an evidence-based review) [RETIRED]
Report of the Quality Standards Subcommittee of the American Academy of Neurology

Dr. Oken's letter questions our recommendation that the available evidence supports the use of vitamin E (1000 units twice a day) in the treatment of AD at the level of a clinical guideline. We are aware of the criticisms of the Sano et al. Study [2] that Dr. Oken cites [3, 4] and appreciate his concerns about the fact that vitamin E was not associated with cognitive benefits in this class 1 study involving 341 AD patients. It was, however, associated with clinical benefit on the combined outcome measure specified a priori as the primary outcome measure. He does not question the classification of the Sano et al. Study as Class I evidence. According to the definitions we used to translate evidence into levels of recommendation, a single Class I study could support the recommendation that an agent be used as a standard of care. The committee elected to recommend vitamin E as a guideline (reflecting moderate clinical certainty) rather than a standard until more evidence is available.

Dr. Oken also suggests that our review of the evidence related to ginkgo biloba extract is incomplete because we did not cite two articles. [5, 6] The implication is these articles would have changed our conclusion that ginkgo biloba is a practice option, but lacks sufficient evidence to be recommended as a treatment guideline or a standard of care. Both articles were identified and reviewed by the Management Committee in the process of evaluating the evidence. As cited in the Practice Parameter article, only Class 1 evidence was used in the review of agents to treat the cognitive symptoms of dementia, and each treatment required an N of at least 20. [1] The first study (standardized criteria) in a three month, randomized, double-blind, placebo-controlled study of 80 mg ginkgo biloba special extract tid versus placebo. There were 21 patients treated with drug, but only 19 treated wit placebo. Therefore, this study was excluded because it did not have at least 20 subjects per treatment group. If it had been included, several of the committee members would have classified the primary outcome measure results as negative based upon overlap between the confidence intervals of test scores for drug versus placebo treated subjects. The second study [6] cited by Dr. Oken compared only nine patients treated with ginkgo biloba extract to nine patients treated with placebo, and was also excluded because of insufficient sample size. The evidence of the use of ginkgo biloba to treat dementia is inconclusive with or without these studies, and therefore, can only be mentioned as a practice option until considerably more information becomes available.

References:

1) Doody R, Stevens J, Beck C et al. Practice Parameter: Management of dementia (an evidence-based review). Neurology 2001; 56:1154-1166.

2) Sano M, Ernesto C, RGT, Klauber M et al. A controlled trial of selegiline, alphatocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's disease cooperative study. New Eng J of Med 1997;336(17):1216-1222. 3) Drachman D, Leber P. Treatment of Alzheimer's disease-searching for a breakthrough, settling for less. New Eng J of Med 1997;336:1245-1247.

4) Tabet N, Birks J, Evans J, Orrel M, Spector A. Vitamin E for Alzheimer's disease. In: Cochrane Database of Systematic Reviews; 2000.

5) Hofferberth B. The efficacy of EGb 761 in patients with senile dementia of the Alzheimer type: A double-blind placebo-controlled study on different levels of investigation. Human Psychopharmacology 1994;9:215- 222.

6) Maurer K, Ihl R, Dierks T, Frolich L. Clinical efficacy of ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type. J Psychiat Res 1997;31:645-655.