June 1, 2000 Researchers led by a UC San Francisco scientist are reporting that hormone replacement therapy (HRT) using estrogen may protect against cognitive decline in women 65 and older. The study of 3,393 women, to be published in the May 23 issue of Neurology, is the first to show that the genes a woman inherits can affect her response to estrogen.
Women who carry a certain variety of a gene called ApoE were half as likely to suffer cognitive deterioration after age 65 if they were using estrogen, said principal investigator Kristine Yaffe, MD, assistant professor of psychiatry, neurology and epidemiology at UCSF and chief of geriatric psychiatry at San Francisco Veterans Affairs Medical Center.
The ApoE (Apolipoprotein E) gene, which has three possible variants or alleles (e2, e3 and e4) is a blueprint for a protein that carries cholesterol and fats between the liver, brain and other tissues.
Estrogen-using women who carry the e2 and e3 variants (inherited as a pair from their parents) experienced less cognitive loss during the seven year study, said Yaffe. The results indicate that estrogen may help prevent cognitive decline in women who carry e2 and e3 alleles, she explained.
The researchers also studied women who carry at least one e4 allele and have a higher risk of developing Alzheimer's Disease (AD), according to previous studies. In these women, estrogen use did not protect against cognitive decline.
Yaffe also reports that estrogen use was associated with less carotid wall thickening or atherosclerosis. The carotid arteries located on either side of the neck carry blood to the brain. "Less atherosclerosis may prevent small vessel strokes that result in mental deterioration as we age," said Yaffe, adding that this mechanism needs further study.
The researchers studied women in four communities of the United States, who were part of the Cardiovascular Health Study (CHS), a long-term study of coronary heart disease and stroke in older adults. Mental function tests, given in each of five to seven years, tracked cognitive decline in women who were asked to report estrogen use on a questionnaire given during each visit. Nearly all of the women gave blood samples containing the DNA necessary for ApoE genotyping.
At each testing point, results were adjusted for factors that vary between estrogen users and non-users (age, education, alcohol consumption habits and body mass) and other risk factors for cognitive decline (age, education, race and stroke history). The researchers excluded the small number of women taking progestins and were not able to determine if estrogen taken with progestins would have the same effect on cognitive decline. Yaffe cautions that more study is also necessary to determine whether HRT taken before age 65 can prevent cognitive decline.
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