Some studies hint that a variety of existing drugs and supplements may be useful in delaying AD or stopping its progression. These studies are preliminary, and their findings would need to be demonstrated in adequately designed and conducted studies before their conclusions can be considered proven, says Katz.
Cholesterol-lowering drugs, anti-inflammatory drugs, antioxidants, and estrogen are some of the substances that have been studied, but study results have been conflicting. These studies don't prove causation, warns Thies of the Alzheimer's Association. "All they really tell us is it's a good place to start doing clinical trials." And researchers are doing just that.
Studies have shown a link between known risk factors for heart disease--high blood pressure, high cholesterol levels, and diets high in saturated fats and trans fats--and an increased risk for AD. There is also evidence that an elevated level of homocysteine, an amino acid in the blood, presents a risk for both heart disease and AD. Further, taking cholesterol-lowering drugs (statins) is associated with a lower occurrence of AD.
"What is good for the heart may be good for the head," says Thies, and healthy lifestyle behaviors such as exercising, eating healthily, and managing blood pressure and cholesterol may be of value in protecting people from AD.
Large-scale clinical trials are being conducted to clarify the link between cardiovascular risk factors and AD. In addition to statins, substances being tested for slowing and preventing AD are folate (a form of B vitamin) and vitamins B6 and B12, which may lower homocysteine levels.
People who take large doses of non-steroidal anti-inflammatory drugs (NSAIDs), commonly used to reduce joint inflammation and pain, have a reduced likelihood of developing AD, according to some studies. NSAIDs, which include over-the-counter aspirin and ibuprofen, as well as some prescription drugs, such as Celebrex (celecoxib), may reduce the inflammation in the brain associated with AD.
None of the studies performed with the anti-inflammatory drugs to date are definitive, cautions Katz, and these drugs would need to be studied in scientifically rigorous trials before the effects of these drugs on AD could be accepted. One of these trials, the Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT), was launched in 2001 to test the effectiveness of some NSAIDs in preventing AD. The study of more than 2,500 healthy participants age 70 and over is sponsored by the NIA and is scheduled to run between five and seven years.
Researchers are also looking at antioxidants to possibly prevent cognitive decline. Antioxidants, such as vitamin E, vitamin C and carotene, may help break down "free radicals"--cell-damaging compounds that are byproducts of normally functioning cells. The natural defenses of cells protect against these compounds, but these protective mechanisms decline as a person ages.
Some study results have suggested that antioxidants may protect against cell damage and lessen the likelihood of getting AD. But a four-year study of nearly 1,000 older people conducted at Columbia University found that consuming carotenes or vitamins C and E either through the diet or by supplements did not decrease the risk of developing AD. "This large-scale study is at variance with earlier indications that these supplements are effective as a treatment for Alzheimer's," says Thies. "This tells us that more work needs to be done before we completely understand the value of these agents." The results of this study are published in the February 2003 issue of Archives of Neurology.
"There are virtually shelf-fuls of compounds capable of acting in an antioxidant fashion," says Thies. One of these, Ginkgo biloba, used for thousands of years in Chinese herbal medicine, has been shown in a small study to result in a modest improvement in cognition, social behavior and performing activities of daily living, such as dressing and eating. A larger study (about 3,000 participants) funded by the National Institutes of Health (NIH) is currently investigating the effectiveness of Ginkgo in preventing or delaying cognitive decline in older adults.
The FDA cautions consumers that some supplements may interact with prescription and over-the-counter medicines and cause serious harm. Check with your doctor or health care provider before taking any dietary supplement, including herbs.
Several epidemiological studies have linked the female hormone estrogen to improved memory and possible delay or prevention of AD in women. But a large, long-term clinical trial sponsored by the NIH has provided evidence to the contrary. In the trial, part of the Women's Health Initiative Memory Study (WHIMS), women 65 and over taking estrogen combined with another hormone, progestin, had twice the rate of dementia, including AD, than those women not taking the hormones. The study, published in the May 28, 2003, issue of JAMA, also found that the hormone combination did not protect against the development of mild cognitive impairment, a form of mental decline less severe than dementia.
New drugs are emerging from the basic science laboratories and moving toward testing in human trials. "The ones furthest along are based on the amyloid hypothesis," says Thies. The hypothesis is that AD starts with the accumulation of amyloid plaques, and that limiting this accumulation will change the progress of AD.
Scientists have isolated enzymes called secretases, which are thought to lead to the formation of beta-amyloid. Secretases are categorized as proteases, the same type of enzymes that are targeted by protease inhibitors to treat AIDS. Drugs called secretase inhibitors are being developed to block beta-amyloid formation, and some of these drugs are now being tested.
Another approach to plaque attack is to stimulate the body's immune system to destroy the beta-amyloid. Scientists developed a vaccine that put amyloid into the blood in the hopes of making antibodies to destroy the plaques. The vaccine was successful in transgenic mice--special mice that were injected with human genes that caused them to develop AD-like plaques. But when tested in a human trial, some people showed inflammation of the brain (encephalitis). Further vaccination was stopped, but study participants continue to be followed. Although this particular vaccine may be disappointing, many scientists believe that the strategy of fighting AD by stimulating the immune system still remains an important potential avenue to slow or prevent the disease.
"We are still searching for the sequence of events where we can intervene and cure the disease without causing harm," says Marcelle Morrison-Bogorad, Ph.D., associate director of the NIA's Neuroscience and Neuropsychology of Aging Program. Morrison-Bogorad notes that scientists may someday be able to inject a substance into the blood to draw amyloid from cerebral spinal fluid and the brain. "This can happen in transgenic mice--we don't know whether it happens in humans yet."