Are there other treatments for Cognitive Decline?

August 27, 2010

Are there other treatments for Cognitive Decline in Alzheimer’s disease?
Strong evidence indicates that vitamin E, taken at a dosage of 1,000 I.U. twice a day, may slow the progression of Alzheimer’s in some people, although the overall impact is minimal. Studies are ongoing, and vitamin E should be used only under a doctor’s supervision.

There has been research into the use of other drugs to treat, stop, or prevent Alzheimer’s, but most have not proved to be effective. Some population-based research studies – called epidemiological studies – have suggested that the female hormone estrogen, statins used to treat high cholesterol, the steroid prednisone, and a group of drugs used to treat arthritis, called non-steroidal anti-inflammatory drugs (NSAIDs) may be protective against Alzheimer’s. While these agents may prove to be effective in preventing or delaying Alzheimer’s – recent studies support such a role for NSAIDs, in particular – studies completed to date indicate that they are not effective treatments for Alzheimer’s. This apparent contradiction may be explained by the fact that once symptoms of Alzheimer’s are evident, the disease processes in the brain may have progressed too far for such agents to be effective. However, if used before symptoms are apparent, these drugs may be able to alter the progression of nerve cell loss and other disease-related changes in the brain, though research proving this effect is inconclusive. More research is needed to determine the effects that these other treatments may have on Alzheimer’s.

Is estrogen an effective treatment for Alzheimer’s disease?
Many recent studies have found that estrogen hormone replacement therapy does not have much effect on the symptoms of Alzheimer’s disease. Estrogen, a hormone that is produced by the ovaries during a woman’s reproductive years, affects brain regions relevant to memory, such as the hippocampus. A large body of data gathered over the past 25 years in animal studies supports the notion that estrogen has some positive effects on memory function. In population-based observational studies (called epidemiologic studies), estrogen use has been associated with a decreased risk of Alzheimer’s and with enhanced cognitive function. It also has both antioxidant and anti-inflammatory effects and enhances the growth of nerve fibers from particular neurons important for memory function. These data have created intense scientific interest in the relationship between estrogen, memory, and cognitive function in humans.

In recent years, the federal government’s lead agency for research on aging, the National Institute on Aging, has supported one Alzheimer’s clinical trial on estrogen in the hope that it might be able to provide evidence on whether estrogen actually affects the progression of the disease. Results of this study indicated that estrogen replacement therapy (ERT) did not slow progression of Alzheimer’s or improve cognitive or functional outcomes in women who have Alzheimer’s. Even if given for a full year, estrogen was not helpful for these women. It should be noted that the findings apply only to a very specific population of older patients who had had Alzheimer’s for some time.

A closely associated study provided similar results. In this study, postmenopausal women with mild to moderate Alzheimer’s disease were treated for 16 weeks with 1.25 mg/day of estrogen. At both 4 and 16 weeks there were no significant differences between treatment and placebo groups on measures of cognition or caregiver-rated functional status. Estrogen did not slow the functional decline associated with Alzheimer’s, and did not improve mood or other disease symptoms.

Another clinical trial examined the effects of estrogen on cognition, mood, and blood flow to the brain in women with mild to moderate Alzheimer’s disease. Blood flow is important because nutrients such as glucose and oxygen reach the brain through the blood stream. The better the blood flow, the more likely a person is to have good cognitive function. This study tested the effect of 1.25 mg of estrogen given without any progesterone (another hormone sometimes given with estrogen) to women in Taipei, Taiwan, who had a diagnosis of mild to moderate AD. Women were given the hormone for 3 months. Again, there was no beneficial effect, either on blood flow or cognitive decline in these women. When taken with data from clinical trials done in the U.S., the data suggest that the negative estrogen findings might be generalizable to older women with Alzheimer’s who are of different races.

Most recently, in May 2003, a five-year follow-up memory component of the large and rigorous Women’s Health Initiative called WHIMS (Women’s Health Initiative Memory Study revealed that healthy women aged 65 and older who took Prempro, a popular combination of estrogen and progestin, had twice the rate of dementia, including Alzheimer’s, as women who did not take the medication. The new findings, add new fuel to the debate over hormone replacement therapy. However, it is important to keep these risks in perspective. Out of 4,500 women in the study, only 61 developed dementia. Forty of those cases occurred in those on hormone replacement (20 were deemed to be Alzheimer’s disease), while 21 cases of dementia (including 12 cases of Alzheimer’s) occurred in those on a placebo. These results confirm that the vast majority of older women who take estrogen will not develop dementia, just as they will not develop breast cancer or have a heart attack as a result of the medicines. There risk, however, is still slightly increased, and women will want to continue to discuss the pros and cons with their doctors.

These studies have found that estrogen does not have a beneficial effect on older women who already have Alzheimer’s, but it is unclear whether normally aging women who take estrogen after menopause will be protected from developing Alzheimer’s or age-related cognitive decline.

National Institute on Aging, “Progress Report on Alzheimer’s Disease” PDF (will open in new window)
Sally A. Shumaker, et al, “Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women: The Women’s Health Initiative Memory Study: A Randomized Controlled Trial” JAMA 2003 289: 2651-2662.
Kristine Yaffe, “Hormone Therapy and the Brain: Deja Vu All Over Again?” JAMA 2003 289: 2717-2719.

Copy by: Brenda Patoine and Toby Bilanow
Reviewed by: Sam Gandy, M.D., Ph.D., Chairman of the Scientific Advisory Board for the Fisher Center for Alzheimer’s Research Foundation


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