Preventing Dementia After Menopause

From the WebMD Archives

May 30, 2000 (Boise, Idaho) -- It's possible that estrogen replacement therapy could protect against mental decline in older women, but it apparently helps to start out with the right genes. Both cognitive decline and atherosclerosis in the carotid arteries are less likely in women over 65 who do not have a particular gene but who do take estrogen, according to a study in the May 23 issue of Neurology.

"I was interested to see whether we could find a difference in estrogen's protective effect depending on someone's genetic background -- looking at the gene-environment interaction," lead author Kristine Yaffe, MD, associate professor of psychiatry, neurology, and epidemiology at the University of California, San Francisco, and chief of geriatric psychiatry at San Francisco Veteran Affairs Medical Center, tells WebRN.

Yaffe and her colleagues recruited 2,718 women participating in the Cardiovascular Health Study, a long-term study of cardiovascular heart disease and stroke among older adults. The women completed at least two cognitive evaluations, supplied information about past and present estrogen use, and allowed measurement of the thickness of their carotid artery walls. Most also consented to genetic testing.

The genetic analysis detected the presence or absence of a gene called ApoE4, which is associated with a greater likelihood of developing Alzheimer's disease (AD). According to the study, 26% of women have the gene.

Study results showed that, among the 74% of older women without ApoE4, those taking estrogen were 50% less likely than those who had never taken the hormone to exhibit signs of cognitive decline. But in the women who did have the gene, estrogen use did not affect the likelihood of mental deterioration.

The same trends emerged with respect to the risk of developing or worsening atherosclerosis. ApoE4-negative women using estrogen had thinner carotid artery walls than those who had never taken estrogen. Test results showed estrogen use among women with ApoE4 did not affect carotid wall thickness. Experts theorize that thickening of the carotid arteries may cause mental deterioration by affecting blood flow to the brain.

Sandra Picot, PhD, RN, thinks the study's findings are plausible, given what's already known about Alzheimer's. "If you think about the area of the brain that's affected by Alzheimer's disease, it is also an area that has quite a few estrogen receptors," says Picot, associate professor and Sonya Ziporkin Gershowitz endowed chair in gerontology at the University of Maryland School of Nursing. "So it makes sense that if you can provide someone with estrogen and they do not [already] have advanced development of dementia, [estrogen] might be helpful [in preventing the disease]."


It's premature to think about widespread clinical application by determining a woman's ApoE4 status, says Yaffe. "At this point, we don't have great preventions [for AD], so it probably doesn't make sense to look at testing everyone. But if we do develop good medicines that prevent AD, we may want to know the E4 status, because those are the people who might preferentially go on therapy."

Both Yaffe and Picot note that the study did not look at women using the more common regimen of an estrogen and progesterone combination for hormone replacement. Picot advises nurses counseling patients about the value of hormone replacement therapy to mention the potential prevention of mental decline as one possible benefit -- along with protection against osteoporosis and some types of heart disease -- of the therapy. However, Picot cautions that the contraindications for estrogen use must also be considered. "We don't want to jump on the bandwagon and think that this is for everybody," she says.

Picot thinks the beauty of this study is its effort to factor in environmental variables while investigating genetic differences. "When we consider that the Human Genome Project is suggesting that we're all about 99.5% alike genetically, this particular set of findings is very impressive and believable."

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