NIA’s program of AD research continues to add to what we know about AD and yield clues about possible ways to prevent the disease. The following sections briefly describe a few other areas that scientists are exploring.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Inflammation in the brain is a common feature of AD, but it is unclear whether this is a cause or an effect of the disease. Some epidemiologic studies suggest an association between a reduced risk of AD and commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, and indomethacin. So far, clinical trials have not demonstrated a benefit for AD from these drugs or from the newer cyclooxygenase-2 (COX-2) inhibitors, such as rofecoxib and celecoxib. However, scientists continue to look for ways to test how other anti-inflammatory drugs might affect the development or progression of AD.
Antioxidants
Damage during aging from highly active molecules called free radicals can build up in nerve cells and result in a loss of cell function, which could contribute to AD. Some population and laboratory studies suggest that antioxidants from dietary supplements or food may provide some protection against this damage (called oxidative damage), but other studies show no effect.
Clinical trials may provide some answers. Several current trials are investigating whether antioxidants, such as vitamins E and C, alpha-lipoic acid, and coenzyme Q, can slow cognitive decline and development of AD.
NIA-sponsored sub-studies to ongoing trials have looked at whether two treatments provide any protection against cognitive decline in women. One sub-study tested low-dose aspirin and antioxidant supplementation in healthy women, and the other tested antioxidant and folate supplements in women who already had heart disease. Initial results indicate that aspirin may provide some benefits for maintaining executive function but has no impact on other cognitive domains. For vitamin E, there was no overall benefit. Analysis of these studies is ongoing.
Another study added to a prostate cancer prevention trial is examining whether taking vitamin E and/or selenium supplements over a period of 7 to 12 years can help prevent memory loss and dementia. Although the primary trial was stopped because the supplements were shown not to prevent prostate cancer, researchers are continuing to follow participants to analyze longer term effects of the supplements.
The Memory Impairment Study compared the use of donepezil (AriceptÒ), vitamin E supplements, or placebo (an inactive substance) in participants with mild cognitive impairment (MCI) to see whether the drugs might delay or prevent progression to AD. People with MCI have more memory problems than normal for people their age, but their symptoms are not as severe as those with AD. More people with MCI, compared with those without MCI, go on to develop AD. The study found that taking vitamin E had no effect on progression to AD. It may be that this antioxidant did not help after memory declines had already started. Donepezil seemed to delay progression to AD during the first year of treatment; however, by the end of the 3-year study there was no benefit from the drug. The U.S. Food and Drug Administration (FDA) has not approved donepezil for treatment of MCI.
Estrogen
The hormone estrogen is produced by a woman’s ovaries during her childbearing years, and its production declines dramatically after menopause. Over the past 25 years, some laboratory and animal research, as well as observational studies in women, have suggested that estrogen may protect the brain. Experts have wondered whether taking estrogen supplements could reduce the risk of AD or slow disease progression.
A number of clinical trials have shown that estrogen does not slow the progression of already-diagnosed AD and is not effective in treating or preventing AD if treatment is begun in later life. For example, a large trial found that women older than 65 who took estrogen (PremarinÒ) alone or estrogen with a synthetic progestin (PremProÒ) were actually at increased risk of developing dementia, including AD. However, some questions, such as whether other forms of estrogen or starting treatment nearer menopause might be more effective, remain unanswered. These questions are now being investigated in clinical trials.
Researchers also are probing estrogen’s possible beneficial effects on the brain. For example, scientists have developed estrogen-like molecules called SERMs (selective estrogen-receptor modulators) that protect against bone loss and other consequences of estrogen loss after menopause. These molecules may retain estrogen’s neuron-protecting ability but may not have some of its other harmful effects on the body, such as increasing the risk of uterine cancer. One large clinical trial showed that raloxifene, a SERM used to prevent and treat osteoporosis and to reduce the incidence of breast cancer in women at high risk for the disease, lowered the risk of MCI in a group of postmenopausal women with osteoporosis. Another clinical trial is testing whether raloxifene can slow the rate of AD progression.
Immunization
Could a vaccine someday prevent AD? Early vaccine studies in mice were so successful in reducing deposits of beta-amyloid and improving brain performance on memory tests that investigators conducted preliminary clinical trials in humans with AD. These studies had to be stopped because life-threatening brain inflammation occurred in some participants. However, scientists are continuing to refine this strategy in animal models of AD, hoping to find ways of maintaining the vaccine’s beneficial effects while reducing the unwanted side effects. Several pharmaceutical companies have obtained permission from the FDA to test several of these new vaccine strategies for safety in early-stage clinical trials.<< Back | Next >>
