Alzheimer's Disease

M.X. Tang, D. Jacobs, Y. Stern, K. Marder, P. Schofield, B. Gurland, H. Andrews, R. Mayeux, "Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease," Lancet, 348:429-32, 1996. (Cited more than 127 times since publication) Comments by Ming-Xin Tang, professor of biostatistics, Gertrude H. Sergievsky Center, Columbia University. Alzheimer's disease, which is characterized by the progressive loss of cognitive function, afflicts about 5 percent to 10 percent of the elderly population in the United States. Although the U.S. Food and Drug Administration has approved some drugs for Alzheimer's, there is still no known effective treatment for the disease. However, a widely cited study by Ming-Xin Tang, a professor of biostatistics at Columbia University's Gertrude H. Sergievsky Center, has given hope that at least the onset of the disease can be delayed in postmenopausal women through the use of estrogen. THE ESTROGEN EFFECT: Columbia biostatistician Ming-Xin Tang led a research team that found that estrogen could delay the onset of Alzheimer's in elderly women. "We won't have a complete understanding of the effect of estrogen until we have clinical trials." - Ming-Xin Tang Five years ago, basic research in neurology first suggested to investigators that estrogen could be effective in the treatment or delay of Alzheimer's. Columbia cell biologists C. Dominique Toran-Allerand and Rajesh C. Miranda --now at Texas A&M--in 1993 found that the hormone helped to promote the synthesis and release of nerve growth factors extensively distributed throughout the basal forebrain of rats. These findings implied that estrogen could play a significant role in the survival and regeneration of brain cells. But clinical evidence for the effect of estrogen at times has been conflicting. Through improved study design, Tang and his research team provided a clearer picture of the potential benefit from estrogen in treating Alzheimer's. In their study, Tang and the Columbia research team gained access to a random sample of 1,282 women who were participating in a community-based study on aging in northern Manhattan, New York City. Each recruit underwent an interview and a medical and neurological examination. Criteria for inclusion in the study included no evidence of cognitive impairment and no history of stroke or Parkinson's disease. Information for estrogen was available for 1,227 of these women, and from this group, 103 did not meet criteria for the study. Of the 1,124 elderly women initially free of Alzheimer's, 156 reported taking estrogen after the onset of menopause, with an average duration of use of six to eight years. Tang says the most significant finding of the study was that estrogen use could delay, but not prevent, the onset of Alzheimer's in elderly women. For example, in the group of women with a history of estrogen use, researchers observed that the incidence of Alzheimer's was 2.7 percent. The incidence rate among controls was 8.4 percent. The research team also found that among women taking estrogen for at least a year who later developed Alzheimer's, onset of the disease was significantly delayed. None of the women in the study who where taking estrogen at the time developed Alzheimer's. Tang says that the Columbia study has captured the attention of scientists and clinicians because previous research concluded that estrogen use had no effect on risk reduction for Alzheimer's. In 1990, a Battell Seattle Research Centers team of investigators found no difference between Alzheimer's patients and controls in frequency of use of estrogen in their case-control study (A.B. Grave et al., Annals of Neurology, 28:766-74, 1990). Four years later, a University of Washington research team reached a similar conclusion when they studied the effects of estrogen-replacement therapy in postmenopausal women (D.E. Brenner et al., American Journal of Epidemiology, 140:262-7, 1994). Tang also notes that any study suggesting a potential therapy for Alzheimer's is bound to get attention. "In the near future, Alzheimer's will become one of the major health concerns in the United States," he explains. "The baby boomer population is aging, and there are still really no known treatments or preventative measures for the disease." Tang, however, notes that further study is needed before researchers can definitely conclude that estrogen can delay the onset of Alzheimer's. "Right now, we have only this observational data, which certainly suggests a benefit from estrogen replacement," Tang says. "This is good information, but it is still incomplete. We won't have a complete understanding of the effect of estrogen until we have clinical trials."

Alzheimer's Disease

The Scientist Staff

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