Alzheimer's research shifts direction, creating potential new therapeutic avenues for people at risk.
Alzheimer's disease is a thief. It robs people of their memories, their ability to reason, and their clarity of thought. Anyone who has known someone with Alzheimer's knows how heartbreaking it can be to watch a spouse, friend, sibling, or parent slip into the fog of dementia. Because this disease has a genetic component, many people also fear that they themselves might slip into the same fog one day.
As of now there has been no treatment that can halt or even significantly slow the progress of Alzheimer's. The four drugs currently approved to treat Alzheimer's—donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne), and memantine (Namenda)—can improve thinking, memory, and behavior. Yet they can't get at the underlying disease process that leads to the steep cognitive decline.
The outlook for people at risk for Alzheimer's may soon become brighter, though, as the direction of research changes. "For the past 20 or even 30 years we've been focused on treating the end stage of Alzheimer's, and we must shift our paradigm to start thinking about prevention," says Dr. Reisa Sperling, director of the Center for Alzheimer's Research and Treatment at Harvard-affiliated Brigham and Women's Hospital.
Plaques and tangles
In Alzheimer's, beta-amyloid plaques and tau tangles damage nerve cells (neurons), interfering with normal thought and memory.
Dr. Sperling and other researchers are currently homing in on a few specific targets for Alzheimer's prevention.
Beta-amyloid plaques. Most of the Alzheimer's studies in progress focus on reducing beta-amyloid, an abnormal collection of proteins that forms hard accumulations called plaques in the brains of people with this disease. Early efforts to eliminate beta-amyloid included vaccines to stimulate the body's immune system to attack the abnormal proteins. However, this approach sometimes also overstimulated the immune system. In 2002, the first large-scale Alzheimer's vaccine trial had to be shut down when a small percentage of participants developed a dangerous brain inflammation called meningoencephalitis.
A newer approach uses lab-grown antibodies called monoclonal antibodies, which target the amyloid without overstimulating the immune system. Monoclonal antibodies currently under investigation for Alzheimer's include bapineuzumab, solanezumab, and crenezumab. It isn't clear yet whether reducing amyloid will change the course of the disease in humans, although it has in animals.
In September 2012, Dr. Sperling and her team announced results from a study on bapineuzumab. Although the drug didn't stop mental decline in people with Alzheimer's, there were indications that it might reduce amyloid levels and limit nerve cell damage, especially if given early in the course of the disease. Evidence so far on solanezumab suggests that it could improve measures of thinking and memory, but only in people with mild Alzheimer's, Dr. Sperling says.
"Unfortunately, these studies probably aren't going to result in a drug coming to the market yet. But these results were encouraging enough for that line of research to go forward in clinical trials," she adds.
Because amyloid deposits appear in the brain a full decade before symptoms appear, the push right now is to treat people as soon as they have evidence of plaques. To that end, Dr. Sperling is launching a three-year study that will use PET scans to examine the brains of about 1,000 people, ages 70 to 85. Those who have signs of amyloid will be treated with a monoclonal antibody—although which specific drug will be used hasn't yet been decided.
Tau tangles. The other target in Alzheimer's drug development is the tangles of proteins in the brain composed of a protein called tau. Like plaques of beta-amyloid, these tangles can destroy neurons and cause dementia. Researchers are currently investigating various therapies to prevent tangles from forming.
Inflammation. Inflammatory processes in the body are implicated in a number of conditions, including heart disease. These same processes might be at work in Alzheimer's, leading to nerve damage in the brain. There is evidence, for example, that people who regularly take nonsteroidal anti-inflammatory drugs (NSAIDs) have a lower incidence of Alzheimer's. Studies are looking at whether other therapies aimed at reducing inflammation might interrupt the Alzheimer's disease process.
Blood vessel health. A network of blood vessels supplies the brain with the oxygen-rich blood it needs to function. Diseases such as high blood pressure, heart disease, stroke, high cholesterol, and diabetes damage these blood vessels and can increase the risk of Alzheimer's. Researchers are studying whether treating these conditions might lower dementia risk.
What you can do today
Until researchers identify effective ways to prevent Alzheimer's, take charge of your memory and cognitive function by staying mentally and physically active. There is good evidence that exercising regularly—incorporating both aerobic activity and strength training—can help protect nerve cells.
Social activity is important too, but staying engaged can be more challenging as you get older. "We've known for a long time that when people retire they become less active and more withdrawn, and that's counterproductive," Dr. Sperling says.
Instead of sitting home and watching TV, get out in the fresh air for a brisk walk or visit a museum with friends. The combination of exercise and social interaction could do wonders for your mental capacity.
Although a cure for Alzheimer's won't happen overnight, Dr. Sperling is cautiously optimistic. "I still am hopeful, because I believe that if we're right about the amyloid hypothesis and we can find a way to intervene earlier, we really will make a dent," she says. "I suspect that's at least five years away, but I don't think it's decades anymore."
Alzheimer's clinical trials
If you have a family history of Alzheimer's and you'd like to take part in a clinical trial, contact the Alzheimer's Association's TrialMatch program—a free service that can help you locate relevant studies in your area. To learn more about this program, call 800-272-3900 or visit: www.alz.org/research/clinical_trials/find_clinical_trials_trialmatch.asp
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