With the number of Alzheimer's victims expected to double or triple in the next 50 years, researchers are scrambling as never before to find treatments and ultimately a cure that could stave off a public health disaster.
Few who have delved into the mysteries of the disease that claimed the life of former President Ronald Reagan dare to predict when breakthroughs will occur. The most optimistic say a cure is at least a decade away.
Backed this year by $679 million in federal funds and more from private sources, researchers are working on multiple fronts. They are testing new medications and old ones, stem cells and vitamins, gene therapies and vaccines. They are studying mice given Alzheimer's genes and the brains of people who died from the disease for clues to its devastating path.
Reagan's death could spur more research.
In mourning the former president yesterday, the Chicago-based Alzheimer's Association lauded Reagan and his wife, Nancy, for raising the visibility of the disease and championing research. The group called for a $40 million increase in federal funding.
Sen. Barbara A. Mikulski of Maryland, the ranking Democrat on the Aging subcommittee, and Sen. Christopher S. Bond, a Missouri Republican, said they would introduce a bill in Reagan's name that would double federal funding to $1.4 billion for Alzheimer's research.
"My family, we know the long goodbye," said Mikulski, who lost her father, a Highlandtown grocer, to the disease.
Sadness and urgency can be heard in the voices of those who have cared for an Alzheimer's patient.
"She said, `It destroys my sense of worthiness,'" said Peter Savage of Roland Park, whose wife, Ina, died of the disease last year. "She would just cry at that."
As the population ages, the number of Americans with Alzheimer's is expected to increase from 4 million to as many as 12 million in the next 50 years.
Though the past 10 years have produced the first drugs that slow the deterioration from Alzheimer's disease, their effects are modest and short-lived. Ina Savage, a Baltimore teacher who spoke five languages, experienced an unusual benefit. In 1998, just weeks after taking Aricept, one of five Alzheimer's drugs now on the market, she could suddenly read a page of print without forgetting the previous one.
The effects lasted three months, long enough to digest a best-seller about the lives of Franklin and Eleanor Roosevelt and discuss with her husband the history of slavery in Brazil. Then she continued her decline.
"In general, people to some extent with Alzheimer's are doing better than a decade ago," said Dr. Paul Fishman, who heads the neurodegenerative disease division at the University of Maryland Medical Center. "They are not cures and they are modestly effective, but they are better than nothing."
Ten percent to 15 percent of people on the drugs can stay at home a few months longer, said Dr. Constantine G. Lyketsos, head of the Alzheimer's Center at the Johns Hopkins School of Medicine.
The disease is named for Dr. Alois Alzheimer, a German neurologist who in 1906 discovered strange clumps and knots in the brain of a woman who died after suffering from a mental disease. Today, it is recognized as the leading type of dementia, one that diminishes not only memory but life's basic functions, including walking and eating.
Like Reagan, victims typically suffer for 10 to 12 years before the disease kills them. At greatest risk are people over 80, though the disease also strikes younger people, including, in rare cases, those in middle age. Ina Savage received the diagnosis in her 50s, and died at 62.
A hallmark of Alzheimer's disease are deposits known as plaque that appear throughout the brain. Researchers aren't sure if the deposits cause Alzheimer's or are byproducts of the disease. Other features are twisted fibers, known as tangles, within brain cells.
"The brain is shrinking, cells are dying, connections are lost," said Dr. Marcelle Morrison-Bogorad, who heads the neuroscience program at the National Institute on Aging.
The drugs generally work by supplying a brain chemical that becomes depleted when Alzheimer's sets in. Today, scientists are looking for treatments that would stop the progress of the disease. One would interfere with a gene that produces a protein that, when clipped apart, forms the plaques. Another would stop the proteins from being clipped.
Other scientists are hoping to harness stem cells to regenerate brain cells killed by Alzheimer's. Mrs. Reagan was a vocal sup- porter of such research, saying that the potential to save lives should outweigh any ethical concerns.
Still others are conducting clinical trials of cholesterol-lowering drugs known as statins, anti-inflammatory medications and antioxidants such as vitamin E, which they hope will prevent Alzheimer's if taken years before symptoms emerge.
Dr. Majid Fotuhi, director of the memory disorders unit at Sinai Hospital, believes that people can reduce their risk of Alzheimer's the same way they reduce risk of a heart attack.
"The most exciting thing in Alzheimer's research today is prevention," he said.
Studies have identified high blood pressure and cholesterol, smoking, diabetes, poor diet and chronic stress, among other things, as risk factors. Aside from eliminating those, Fotuhi said, patients can protect their brains by reading, doing crosswords and even socializing.
"When you do exercise with your muscles, your muscles get stronger," he said. "The same thing happens with the brain. Neurons get stronger."
Sun staff writers Erika Niedowski and Kimberly A.C. Wilson contributed to this article.