Good News, Bad News on Alzheimer's Prevention

Many Americans believe that use of the herb Ginkgo biloba can help stave off development of Alzheimer's disease. However, results from a large clinical trial are sure to disappoint ginkgo proponents.

The trial, headed by Steven DeKosky, M.D., of the University of Virginia and a leading Alzheimer's scientist, was conducted at five academic medical centers throughout the United States. It included more than 3,000 community volunteers aged 75 or older with either normal cognition or mild cognitive impairment. It used a randomized, placebo-controlled, double-blind design.

Half the subjects took 120 mg of ginkgo twice a day, and half took a placebo twice a day. Subjects were evaluated every six months for dementia over the following six years. At the end of the six years, 523 subjects had developed dementia—277 in the ginkgo group and 246 in the placebo group.

Moreover, when the researchers looked to see whether ginkgo might have had an effect on just the incidence of Alzheimer's, not on the incidence of various types of dementia, they still failed to find a preventive effect for gingko, they concluded.

The study was published in the November 19, 2008, Journal of the American Medical Association.

One strength of the study was that the Gingko biloba extract tested was a standardized formulation with specific amounts of active ingredients—in fact, the world's most clinically tested gingko extract. One weakness of the study was that only subjects 75 years of age or older were used. So it is still possible that ginkgo might be able to prevent Alzheimer's if people start taking it earlier in their lives, DeKosky and his group speculated.

Even if that is not the case, ginkgo may well counter symptoms of Alzheimer's, Hyla Cass, M.D., a psychiatrist in Pacific Palisades, Calif., and an authority on alternative and complementary medicine, told Psychiatric News. “There are compelling data showing [its] benefits ... in treating symptoms of dementia....”

For instance, in one randomized, placebo-controlled, double-blind trial, ginkgo was found to be as effective as donepezil in treating Alzheimer's. Donepezil is one of the drugs approved by the Food and Drug Administration for Alzheimer's.

Further, 11 clinical trials have suggested that ginkgo can improve the attention, memory, and cognitive speed of healthy, cognitively intact subjects, Cass pointed out. So even if ginkgo cannot halt the development or progression of Alzheimer's, it may still enhance mental processes in people without the disease, she said.

Meanwhile, somewhat more encouraging news on the Alzheimer's prevention front was published by Norwegian researchers in the November 2008 International Journal of Geriatric Psychiatry—that education may be able to offset people's genetic liability for Alzheimer's. The major investigator was Sigrid Sando, M.D., Ph.D., a consultant neurologist at St. Olav's Hospital in Trondheim.

Education might protect against Alzheimer's, some past studies have suggested. The apolipoprotein E (APOE) e4 gene variant is one of the strongest documented risk factors for Alzheimer's. Sando and her coworkers investigated whether the level of education that people have attained might offset any e4 gene variant vulnerability for Alzheimer's that they possess.

Their case-control study included 373 subjects with Alzheimer's and 559 healthy controls. They evaluated all of the subjects for the types of APOE gene variants they possessed. Not surprisingly, they found that the chances of developing Alzheimer's were 4.4 times greater for persons with one e4 variant than for persons without such a variant, and that the chances were 13.1 times greater for persons with two e4 variants than for persons without such a variant.

Even if subjects had one or two e4 variants, their odds of getting Alzheimer's were significantly less if they had achieved a higher level of education (eight to nine years) than if they had achieved only a lower one (six to seven years). What's more, the protective effect seemed to exist in a dose-dependent manner—those with 10 to 18 years of education were even better protected than those with eight to nine years of education. Thus, even if the APOE e4 gene variant is present, a greater amount of education can help protect against Alzheimer's, Sando and her group concluded in their report.

Education may offer protection directly, Sando and her team speculated—for example, it is possible that a brain that has been challenged by education is better able to fight off brain pathology than is a brain less educationally challenged. Or it may be a proxy for some other protective factor—say, good nutrition or good socioeconomic conditions during childhood.

The gingko study was financed by the National Center for Complementary and Alternative Medicine, the National Institute on Aging, and several other institutes and offices. Schwabe Pharmaceuticals in Germany donated the gingko tablets and identical placebos in blister packs for the study. The education study was funded by the National Institutes of Health and the Research Council of Norway.

An abstract of “Ginkgo Bilobafor Prevention of Dementia” is posted at<http://jama.ama-assn.org/cgi/content/abstract/300/19/2253>. An abstract of “Risk-Reducing Effect of Education in Alzheimer's Disease” is posted at<www3.interscience.wiley.com/journal/119179595/abstract>.▪