In Brief

Postmenopausal women with Alzheimer's disease who undergo long-term estrogen replacement therapy (ERT) may make their memory loss worse, according to a study in the October issue of Behavioral Neuroscience (Vol. 116, No. 5).

In the research, Lisa Marriott and colleagues at the Arizona Research Laboratories at the University of Arizona used female rats to model the effects of long-term ERT on women with existing brain inflammation, which occurs in Alzheimer's. Although female rats do not undergo ovarian failure as they age, when the ovaries are removed, rats experience genetic alterations similar to human menopause.

Rats were tested in a water maze task, enabling the researchers to study the interaction of two conditions that exist in the brains of female Alzheimer's patients: neuroinflammation and presence or absence of estrogen. Removal of the ovaries was not enough to impair the rats' performance in the maze, but introducing either sustained ERT or brain inflammation caused memory loss.

When researchers combined ERT and inflammation, they saw significantly worsened cognitive performance beyond that produced by either one alone. Even the small doses of estrogen provided in the ERT were enough to impair performance when given over the long term, Marriott notes.

"When considered together, the results of this and other clinical trials suggest a pattern of beneficial effects on cognitive function after relatively short-term ERT," the authors say. "However, this beneficial effect is attenuated, and possibly reversed, after much longer treatment regimens." The results parallel those of a 2000 study in the Journal of the American Medical Association showing that women receiving sustained ERT declined more than women receiving a placebo.

ERT contains a constant dose of estrogen, and the researchers suggest that "a therapy designed to mimic the natural cycle of gonadal hormone fluctuation may provide a more effective therapy to slow the progression" of Alzheimer's in women.