The National Institute on Aging (NIA), part of the National Institutes of Health (NIH), is the lead Federal agency for Alzheimer’s Disease (AD) research. NIA-supported scientists are testing a number of drugs to see if they prevent Alzheimer’s, slow the disease, or help reduce symptoms. Some ideas that seem promising turn out to have little or no benefit when they are carefully studied in a clinical trial. Researchers undertake clinical trials to learn whether treatments that appear promising in observational and animal studies actually are safe and effective in people.
Mild Cognitive Impairment. During the past several years, scientists have focused on a type of memory change called mild cognitive impairment (MCI), which is different from both AD and normal age-related memory change. People with MCI have ongoing memory problems, but they do not have other losses such as confusion, attention problems, and difficulty with language. The NIA-funded Memory Impairment Study compared donepezil (Aricept), vitamin E, or placebo in participants with MCI to see whether the drugs might delay or prevent progression to AD. The study found that the group with MCI taking the drug donepezil were at reduced risk of progressing to AD for the first 18 months of a 3-year study when compared with their counterparts on placebo. The reduced risk of progressing from MCI to a diagnosis of AD among participants on donepezil disappeared after 18 months, and by the end of the study, the probability of progressing to AD was the same in the two groups. Vitamin E had no effect at any time point in the study when compared with placebo.
Neuroimaging. Scientists are finding that damage to parts of the brain involved in memory, such as the hippocampus, can sometimes be seen on brain scans before symptoms of the disease occur. An NIA public-private partnership—the AD Neuroimaging Initiative (ADNI)—is a large study that will determine whether magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, or other imaging or biological markers, can see early AD changes or measure disease progression. The project is designed to help speed clinical trials and find new ways to determine the effectiveness of treatments. For more information on ADNI, call the NIA’s Alzheimer’s Disease Education and Referral (ADEAR) Center at 1-800-438-4380, or visit www.alzheimers.org.
AD Genetics. The NIA is sponsoring the AD Genetics Study to learn more about risk factor genes for late onset AD. To participate in this study, families with two or more living siblings diagnosed with AD should contact the National Cell Repository for AD toll-free at 1-800-526-2839. Information may also be requested through the study’s website: http://ncrad.iu.edu.
Inflammation. There is evidence that inflammation in the brain may contribute to AD damage. Some studies have suggested that drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) might help slow the progression of AD, but clinical trials thus far have not demonstrated a benefit from these drugs. A clinical trial studying two of these drugs, rofecoxib (Vioxx) and naproxen (Aleve) showed that they did not delay the progression of AD in people who already have the disease. Another trial, testing whether the NSAIDs celecoxib (Celebrex) and naproxen could prevent AD in healthy older people at risk of the disease, has been suspended. However, investigators are continuing to follow the participants and are examining data regarding possible cardiovascular risk. Researchers are continuing to look for ways to test how other anti-inflammatory drugs might affect the development or progression of AD.
Antioxidants. Several years ago, a clinical trial showed that vitamin E slowed the progress of some consequences of AD by about 7 months. Additional studies are investigating whether antioxidants—vitamins E and C—can slow AD. Another clinical trial is examining whether vitamin E and/or selenium supplements can prevent AD or cognitive decline, and additional studies on other antioxidants are ongoing or being planned.
Ginkgo biloba. Early studies suggested that extracts from the leaves of the ginkgo biloba tree may be of some help in treating AD symptoms. There is no evidence yet that ginkgo biloba will cure or prevent AD, but scientists now are trying to find out in a clinical trial whether ginkgo biloba can delay cognitive decline or prevent dementia in older people.
Estrogen. Some studies have suggested that estrogen used by women to treat the symptoms of menopause also protects the brain. Experts also wondered whether using estrogen could reduce the risk of AD or slow the disease. Clinical trials to test estrogen, however, have not shown that estrogen can slow the progression of already diagnosed AD. And one study found that women over the age of 65 who used estrogen with a progestin were at greater risk of dementia, including AD, and that older women using only estrogen could also increase their chance of developing dementia.
Scientists believe that more research is needed to find out if estrogen may play some role in AD. They would like to know whether starting estrogen therapy around the time of menopause, rather than at age 65 or older, will protect memory or prevent AD.