EMBARGOED by ARCHIVES OF NEUROLOGY for 4 p.m. EST Monday, Feb. 17, 2003

Increased Estrogen Levels Do Not Correlate with Changes in Cognition
In Postmenopausal Women with Alzheimer's

In confirmation of previous research, and contrary to findings from two recent studies, scientists at the University of California, San Diego (UCSD) School of Medicine have shown that increased levels of estrogen do not correlate with changes in cognitive functioning in postmenopausal women with Alzheimer's disease.

The new study, published in the February issue of the American Medical Association's Archives of Neurology, found that elevations in hormone levels did not predict cognitive test scores nor other neuropsychological measures in 120 women with Alzheimer's disease who were given various levels of Premarin, a hormone-replacement therapy that raises the levels of the hormones estradiol and estrone.

Alzheimer's disease is the most common cause of dementia in the United States, affecting approximately 4 million individuals, and occurs with a higher frequency in women. Although some physicians believed that women with Alzheimer's disease who took estrogen experienced improved cognition, three studies in 2000 showed no correlation between estrogen and cognitive improvement. One of those was a multi-center trial published in the Journal of the American Medical Association by the Alzheimer's Disease Cooperative Study, directed by Leon Thal, M.D., UCSD professor of neurosciences and a neurologist with the San Diego VA Healthcare System.

Recently, however, two small clinical trials (with 12 and 20 women) had different results. Investigators reported that higher doses of estrogen, delivered in patch form, improved attention and verbal memory in the two small groups of women.

"In order to investigate an association between estradiol and estrone levels and measures of cognitive function, we studied 120 postmenopausal women with Alzheimer's disease over a one-year period," Thal said. "We attained the same high levels of hormone that the two small clinical trials attained, but our larger study showed no improvement in cognition."

Of the 120 women, 39 received a placebo, 42 received 0.625 mg of Premarin, and 39 were given 1.25 mg of Premarin. Throughout the 12-month period, blood samples were drawn to assess estradiol and estrone levels. Participants also took several tests to determine the relationship between a change in hormone levels and a change in cognition. These included seven selected neuropsychological measures as well as cognitive tests such as the Mini-Mental State Exaination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog), and the Clinical Demential Rating (CDR) Scale.

The study was funded by the National Institute on Aging, with Premarin provided by Wyeth-Ayerst. In addition to Thal, authors were Michael Grundman, M.D., MPH, and Ronald G. Thomas, Ph.D., UCSD; Ruth Mulnard, R.N., DNSc, University of California, Irvine; Mary Sano, Ph.D., Sergievsky Center, Columbia University, New York; and Lon Schneider, M.D., Keck School of Medicine, University of Southern California, Los Angeles.

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