Natural Estrogen May Improve Cognition for Alzheimer's Disease Patients

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Madison, Wisconsin - Post-menopausal women who had mild to moderate Alzheimer's disease and who wore a skin patch with natural estrogen for three months did better on cognitive tests than women who did not wear the patch, according to new findings by the University of Wisconsin School of Medicine and Public Health (SMPH).

The findings are published as an early online version of the Journal of Alzheimer's Disease and are scheduled for publication in the September issue

The study shows that using a natural form of estrogen called estradiol, for short periods of time, may be cognitively beneficial for post-menopausal women with mild to moderate Alzheimer's disease," said Whitney Wharton, lead author and researcher at the UW School of Medicine and Public Health's Alzheimer's Disease Research Center (ADRC).



In the study, 43 post-menopausal women with mild to moderate Alzheimer's disease were enrolled at the University of Wisconsin SMPH ADRC or the University of Washington in Seattle.



Women were randomly assigned to one of five different treatment plans in the randomized, placebo-controlled, double-blind parallel group study: low dose estradiol patch with a placebo tablet or a 2.5 mg tablet of progesterone (medroxyprogesterone); high dose patch with placebo tablet or 2.5 mg tablet of progesterone; placebo skin patch with a placebo tablet.



The study participants underwent cognitive testing before, and at various intervals during, the study. The main result of the study was that women who received estradiol performed better on multiple cognitive tests than women who were assigned to the placebo group.



Also, the cognitive improvements were directly related to estradiol levels. Estradiol is a naturally occurring estrogen predominant in women before menopause. Wharton says estrogen is likely associated with the hippocampus, an area of the brain that has many estrogen receptors and is associated with Alzheimer's disease.




Video: Wharton talks about what we can learn from the study.


Wharton said it's important to realize that estradiol is different from a popular hormone-replacement drug that contains a compound called conjugated equine estrogen (CEE). The compound is not naturally occurring in humans like estradiol.

CEE, the most widely used estrogen used for hormone therapy in the U.S., was the estrogen studied in the landmark Women's Health Initiative (WHI) study and the Women's Health Initiative Memory Study (WHIMS).

The WHI and WHIMS found that hormone replacement therapies using CEE might be associated with increased risk of cardiovascular disease and dementia.

"We know that Alzheimer's is associated with a build-up of amyloid plaques in the brain and we know from basic science studies, that estradiol interacts with, and breaks down, those plaques," said Wharton.

In contrast to the currently FDA-approved Alzheimer's disease drugs, estradiol may actually affect the neuropathology of Alzheimer's disease. Wharton says current drugs treat symptoms like memory loss and mood, but do not change brain mechanisms involved in the disease, such as amyloid plaques.

Wharton says because there are different types of estrogens, the findings about CEE should not be generalized to all forms of estrogen, including estradiol. Wharton says the next step for the research is to replicate the findings.

"We can say that an estradiol skin patch, used for three months or less, appears to improve cognition in post-menopausal women with mild to moderate Alzheimer's disease," said Wharton. "But there is a need for larger trials with more women over longer periods of time to see if estradiol could serve as an alternative therapy for Alzheimer's disease, or one day help scientists learn how to prevent the disease."

The study was funded by the National Institutes of Health and used the resources of the universities of Wisconsin and Washington Department of Medicine Division of Geriatrics and Gerontology, and the Geriatric Research Education and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital in Madison and the Veterans Affairs Puget Sound Health Care System in Seattle