Different types of research -- basic, translational, and clinical research -- are conducted to find ways to treat or prevent Alzheimer's disease. This section looks at clinical research in Alzheimer's disease.
What Is Clinical Research?
Clinical research is medical research involving people. It includes both clinical studies and clinical trials. Clinical studies observe and gather information about large groups of people. Clinical trials test an intervention such as a drug, therapy, medical device, or behavior in many people to see if it is safe and effective.
What a Clinical Study Can Reveal
A clinical study, such as an epidemiological (observational) study, can show if a behavior or situation is associated with Alzheimer's, but it cannot prove that they actually cause or prevent the disease. Other types of research -- test tube and animal studies -- better control the various factors that might influence results. They allow scientists to be more certain about why they get the results they do. These types of studies help researchers identify what should be tested in clinical trials, but the findings may not be the same in humans as in tissue culture or animals.
What Are Clinical Trials?
The best way to find out whether a behavior, drug, or other therapy actually slows, delays, or prevents a disease such as Alzheimer's is through a clinical trial. Clinical trials test interventions in many people to see if they are safe and effective. Trials may compare a potential new treatment with a standard drug or placebo (a mock treatment). Or, they may study whether a certain behavior or condition affects the progress of Alzheimer's or the chances of developing it.
Advances in knowledge gained from basic research and clinical studies about the way Alzheimer's develops and the risk factors associated with it have made it possible for researchers to set up more clinical trials and study more types of interventions.
The National Institutes of Health (NIH), pharmaceutical companies, and other researchers are conducting many clinical trials to test possible new treatments that may
- improve memory, thinking, and reasoning skills in people with Alzheimer's
- relieve the behavior problems of Alzheimer's, such as aggression and agitation
- slow down the disease
- prevent or delay the disease.
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Clinical Trials on Heart Disease and Diabetes Treatments
Several clinical trials are studying whether treatments for heart disease and diabetes can improve memory and thinking skills in people with Alzheimer's or mild cognitive impairment. Some scientists have found that these chronic diseases, which affect the body's blood vessels, are associated with a higher risk of Alzheimer's.
Clinical trials have studied the effects on mental decline of statins, drugs that lower cholesterol. While clinical trials among people with Alzheimer's have not shown a benefit from statins, research is underway to find out if statins can be of benefit in the earlier stages of the disease.
Other trials are looking at how drugs that lower blood pressure and cholesterol affect thinking in people with diabetes and whether intensive diabetes treatment can slow down a decline in thinking skills. Newer trials are studying diabetes-related treatments to see if they improve thinking skills or prevent them from getting worse. These diabetes treatments include the drugs metformin, rosiglitazone, and an insulin nasal spray.
Clinical Trials Involving Women
Clinical trials have found that estrogen -- taken by some women to help relieve menopause symptoms -- does not slow down Alzheimer's disease or prevent it if treatment begins later in life. It may even increase the chances of getting dementia if it is used with another hormone called progestin. New clinical trials are studying whether other forms of estrogen or treatment that starts closer to the age of menopause, rather than at age 65 or older, might be more effective in protecting memory or preventing Alzheimer's.
Also of interest to women is a clinical trial that is testing whether raloxifene, a drug used to prevent and treat bone disease, can slow down Alzheimer's disease. An earlier clinical trial showed that raloxifene lowered the risk of mild cognitive impairment in women who had gone through menopause.
Clinical Trials and NSAIDS
Inflammation in the brain is a common feature of Alzheimer's disease, but it is unclear whether this is a cause or an effect of the disease. Past observational studies suggested a link between nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, and a lower risk of Alzheimer's. So far, clinical trials have not shown that these drugs benefit a person with Alzheimer's. However, scientists continue to look at how other anti-inflammatory drugs might affect the way Alzheimer's disease develops or progresses.
Vaccine Studies and Other Trials
Could a vaccine against the protein amyloid someday prevent Alzheimer's? Early vaccine studies in mice reduced plaques in the brain and improved performance on memory tests. But when they were done in humans, they had to be stopped because some people experienced harmful side effects. Scientists are continuing to study different kinds of vaccines, and several drug companies are testing the safety of new vaccines in early-stage clinical trials.
In a related trial sponsored by NIA, scientists are testing whether "passive" vaccination with an FDA-approved drug called IGIV can successfully treat people with Alzheimer's. Earlier studies showed that IGIV helped remove plaques from the brain.
Many other trials are testing possible new treatments for Alzheimer's disease. They include a clinical trial to see if nerve growth factor, which helps certain nerve cells survive and grow in the brain, can slow Alzheimer's in people with mild to moderate disease. In another trial, scientists are testing the effect of resveratrol, which helps brain cells survive, on the thinking skills of people with mild to moderate disease.
What Role Might Diet and Exercise Play?
In addition to possible new treatments for Alzheimer's, scientists are looking for ways to prevent the disease. Observational studies that look at possible links between some aspect of a person's lifestyle -- such as diet or exercise -- and Alzheimer's or dementia have provided some clues. For example, one observational study found that people who ate a "Mediterranean" diet had a reduced risk of Alzheimer's, but it is not clear if the diet itself reduced their risk. This style of eating includes lots of fruits, vegetables, and whole grains, a fair amount of fish, some meat and poultry, small amounts of sugar and dairy products, plus olive oil and red wine. Scientists are also looking at the effect that DHA (docosahexaenoic acid), an omega-3 fatty acid found in some fish, might have on people with Alzheimer's.
Some clinical trials are testing whether food or dietary supplements containing antioxidants can delay or prevent the mental decline associated with Alzheimer's disease. Antioxidants fight damage to nerve cells caused by molecules called free radicals. Some, but not all, studies have found that antioxidants might protect against this damage. Scientists are continuing to study antioxidants such as vitamins E and C.
Emerging evidence suggests that physical activity might be good for our brains as well as our hearts and waistlines. In one observational study, the risk of Alzheimer's disease was 35 to 40 percent lower in older adults who exercised for at least 15 minutes three or more times a week than in those who exercised fewer than three times a week. One clinical trial to test the idea showed increased brain activity, at least in the short term, in older adults who took part in a program of brisk walking for 6 months. These results are promising, and more clinical trials are underway to find out if physical activity can actually prevent or delay Alzheimer's.
Can Mentally Stimulating Activities Help?
Observational studies have also found that keeping the brain active may be associated with a reduced risk of Alzheimer's. Researchers have found that mentally stimulating activities like reading newspapers, playing games, and visiting museums may help keep your brain sharp.
In one recent clinical trial, computer-based brain exercises helped adults age 65 and older with mild memory impairment improve their reasoning skills or how quickly they processed information. Older adults with normal memory, but not those with impaired memory, improved their memorization skills after receiving memory training. All of these improvements were still noticeable 5 years after the training. The researchers concluded that short-term training in certain mental activities can produce lasting improvements in older adults' thinking skills and quality of life.
In a study observing nuns, priests, and brothers known as the Religious Orders study, researchers asked more than 700 participants to describe the amount of time they spent in mentally stimulating activities. These activities included listening to the radio, reading newspapers, playing puzzle games, and going to museums. After four years, the risk of developing Alzheimer's was 47 percent lower on average for those who did these mentally stimulating activities most frequently than for those who did them least frequently.
Can Social Engagement Slow Mental Decline?
Interacting with friends might help prevent or slow down mental decline. Data from the NIA-funded Chicago Health and Aging Project, an observational study, showed that people who socialized a lot had higher thinking skills than people who did not. They also had a slower decline in thinking skills as they got older. More research is needed to see if socializing does, in fact, play a direct role in preventing Alzheimer's disease.
Taking Part in Clinical Trials
People with Alzheimer's disease, those with mild cognitive impairment (MCI), and healthy people with no memory problems who want to help scientists test new treatments may be able to take part in clinical trials. Results of these trials are used to improve prevention and treatment methods. Some ideas that seem promising turn out to have little or no benefit when they are carefully studied in a clinical trial. (For more about participating in research, click on http://nihseniorhealth.gov/alzheimersdisease/participatinginresearch/01.html.)
Why Clinical Research Is Important
Scientists have come a long way in their understanding of Alzheimer's disease. Findings from years of research have begun to clarify differences among normal age-related memory changes, mild cognitive impairment, and Alzheimer's disease. Scientists also have made great progress in defining the changes that take place in the Alzheimer's disease brain. This research allows them to identify the best possible targets for treatment.