An Alzheimer's diagnosis means something very different today than when former president Ronald Reagan announced 10 years ago that he had the illness: More than any other Alzheimer's patient in history, Reagan -- with his fame and sunny personality -- dramatically reduced the stigma attached to the deadly degenerative disease, advocates say.
Nancy Reagan, furthermore, has championed the cause of Alzheimer's patients with the kind of clout that few other caregivers could wield, and the Reagan name has helped raise millions for research. Nancy Reagan has also led the fight against federal restrictions on embryonic stem cell research -- discreetly challenging President Reagan's most prominent admirer, President Bush, who imposed the restrictive policy.
Although the frustrating, day-to-day reality is that new drugs for Alzheimer's disease have limited benefits, researchers say recent discoveries have closed major scientific gaps and that developing more effective treatments is now only a matter of public and political commitment -- support that may be forthcoming as the nation commemorates Reagan's life and death.
"We will cure Alzheimer's disease as quickly as you want us to," said John Trojanowski, director of the University of Pennsylvania's Alzheimer's Disease Center. "The limiting step is not knowledge, but resources."
About 4 million Americans suffer from Alzheimer's. Because the single biggest risk factor is age, a tidal wave of cases is expected to swamp the health care system as the baby-boom generation ages. By the time they turn 85, one in two Americans has the disease.
When Reagan announced his illness in 1994, Alzheimer's advocates were still struggling to convince many families that the fading memory and debilitating loss of function that patients experience were not just inevitable aspects of aging. Many patients hid their illness, and the fact that far fewer do so today is a tribute to Reagan, said Sam Gandy of the Alzheimer's Association, a national nonprofit advocacy organization.
"Reagan helped make the world aware of that -- that this was a disease," Gandy said. "The stigma is not completely gone, but the Reagans have done more than anyone else to smash that."
In 1995, the Reagans launched the Ronald and Nancy Reagan Research Institute at the association, which Gandy said has helped to raise and distribute about $15 million for research into the disease. Nancy Reagan is an honorary board member at the association, and President Reagan's daughter Maureen was an active board member until her death in 2001.
Ten years ago, Alzheimer's experts were grappling with a confusing array of clues, symptoms, genes and causes for the disease.
The center of gravity has increasingly shifted to the role of tiny particles in the brains of Alzheimer's patients. The particles, called plaque, were discovered first during autopsies, and researchers had no way of knowing whether they were a result of the disease -- or a cause of it. Research in the past 10 years strongly suggests the latter.
Three approaches to eliminating plaque are in various stages of testing. The first involves vaccinating patients against plaque -- triggering the immune system to treat it as an intruder. In animal experiments, a vaccine has protected mice that are genetically prone to developing plaque.
A human safety trial of the vaccination was successful, but the Food and Drug Administration halted the next trial when 5 percent of patients developed encephalitis -- an inflammation of the brain triggered by the body's immune response, Gandy said. Still, he said, results to be presented next month at an international Alzheimer's conference in Philadelphia show that patients with the best immune response experienced a slower decline in their mental capacity.
Another approach is to develop medicines that can disperse plaque, Gandy said. A third is to interfere with the enzymes that help plaque build up. There is evidence that some commonly used drugs, including cholesterol-lowering statins and the painkiller ibuprofen, can influence the process. Results from one study on this issue will also be presented in Philadelphia, Gandy said.
Some of the treatment approaches involve older compounds no longer under patent, which has limited the interest of the pharmaceutical industry, said Trojanowski, of Penn's Alzheimer's Disease Center. One federal program is funding research into treatments such as vitamin E and estrogen -- which may have a protective effect.
Stem cell research is not immediately practical in Alzheimer's disease, because it would involve "a zillion little surgeries" to implant cells all over the brain, Gandy said. Still, the Alzheimer's Association backs it: "It may be more promising in the short term for other diseases, but Alzheimer's disease scientists can learn a lot from it."
Alzheimer's patients are being treated with drugs such as Aricept that are called acetyl cholinesterase inhibitors. Last year, the FDA approved a new type of drug that blocks a neurotransmitter called glutamate. Both types slow cognitive decline, but neither gets at the cause of the illness.
None of the existing drugs has made a significant dent in the helpless frustration that millions of caregivers experience daily, as Nancy Reagan has repeatedly described, while watching a loved one slowly slip away, lose basic abilities to function and even, in the end, fail to recognize the spouse and children who care for them.
"Every doctor and every relative has to feel: Is this all we've got?" said Marcelle Morrison-Bogorad, associate director of the neuroscience and neuropsychology of aging program at the National Institute on Aging. "The answer right now is yes."
Morrison-Bogorad holds out great hope for the newer approaches but says resources are a problem. Budget pressures have led the institute to cut spending this year.
"The landing hasn't been soft," she said. The institute will spend $658 million on Alzheimer's research this year. "The thing that worries me is that something we can't fund this year will be the answer," she said.
This week, Sen. Barbara A. Mikulski (D-Md.) and Sen. Christopher S. Bond (R-Mo.) announced they would introduce legislation in Reagan's honor that would double funding for Alzheimer's research at the National Institutes of Health.
Other research in the past decade has helped to identify imaging techniques that might one day help to spot plaque before symptoms are apparent. Morrison-Bogorad said that changes in the brain may start as many as 20 years before diagnosis.
Trojanowski said that one of the biggest developments in the past 10 years is a sense that several brain disorders might be linked.
"Proteins that are no longer functional become debris, and if the brain fails to clear them, problems arise in the same way as if you didn't take the trash out of your house for a year," he said. Similar mechanisms may underlie Alzheimer's disease, Parkinson's disease and a lesser-known condition called frontotemporal dementia.
The proteins may build up because the body produces too many, or the processes to clear them fail, Trojanowski said, just as traffic gets clogged at rush hour or if there is an accident on the road.
Trying to prevent Alzheimer's is also a major focus of research. Joe Verghese, an assistant professor of neurology at the Albert Einstein College of Medicine in New York, said a growing body of evidence points to the importance of stimulating leisure activity.
Playing chess once a week may reduce the risk of dementia by about 7 percent, he said. Playing three times a week may reduce it by 21 percent. A study he conducted last year, Verghese said, along with other research, suggests that people who pursued intellectually challenging work over their lifetime have a much lower risk. Writing, solving crossword puzzles or playing board games all seem to help.
Awareness of the preventive value of both physical and mental activity has also grown since Reagan's Alzheimer's was diagnosed, but Verghese said the need for systematic prevention studies is urgent. The federal government has started funding such trials, but "to do a real prevention trial, you need $6 [million] to $10 million a year, and you need to keep on for eight to 10 years," Morrison-Bogorad said.
How soon will researchers get to a cure?
"I can't say if it is going to be five years or 50 years," Gandy said, "but I think, for the first time, we are on the right track."