A drug prescribed for the prevention of osteoporosis reduced women's risk of mild cognitive impairment by 33 percent in a worldwide clinical trial led by researchers at San Francisco VA Medical Center (SFVAMC).
The drug, raloxifene, modulates the activity of the hormone estrogen. The finding was published in the April 2005 issue of the American Journal of Psychiatry.
Mild cognitive impairment (MCI) affects more than one-third of women and one-fifth of men aged 65 and older. It reduces short-term memory and is associated with a significantly increased risk of Alzheimer's disease.
"No other intervention has been proven to reduce the risk of mild cognitive impairment," says Kristine Yaffe, MD, the principal investigator of the trial. Yaffe is UCSF associate professor of psychiatry, neurology and epidemiology and chief of geriatric psychiatry at SFVAMC.
Raloxifene is one of the most broadly prescribed drugs for the treatment of osteoporosis (it is also used to treat breast cancer). It is manufactured by Eli Lilly, which sponsored the trial, called the Multiple Outcomes of Raloxifene Evaluation (MORE).
In the MORE trial, which took place at 180 clinical sites in 25 countries, 7,705 postmenopausal women with osteoporosis were randomly assigned to take a daily dose of either 120 milligrams of raloxifene, 60 milligrams of raloxifene, or a placebo for three years. Participants at 161 sites -- 7,023 women -- were measured for cognitive impairment at the beginning of the study and every year thereafter; cognitively impaired women were kept in the study.
Over the course of the trial, 1,637 women dropped out. At the end of the study, the remaining 5,386 were evaluated for dementia. In those women, the 120 milligram dose conferred a 33 percent lower risk of developing mild cognitive impairment when compared with the 60 milligram dose and with placebo. The 60 milligram dose offered no apparent prevention of cognitive impairment. While researchers also observed a reduced risk of developing Alzheimer's disease, that reduction was of borderline statistical significance.
Like all drugs in its class, known as selective estrogen receptor modulators, raloxifene acts like an estrogen in some tissues and as an antiestrogen in others. The authors were unable from this study to determine the mechanism of action responsible for their finding, and whether the effect was due to the drug acting like an estrogen or an antiestrogen in the brain. However, they wrote, given that other studies have shown that estrogen reduces the risk of Alzheimer's disease and cognitive impairment, it is most likely that raloxifene has an estrogen-like effect on the central nervous system. According to Yaffe, it is probable that because the preventive effect involves estrogen, a female hormone, the results of the study do not apply to men; however, the study has no data to support this.