Alzheimer’s Focus Shifts to Delay, Not Cure
The hottest trend in medical research on Alzheimer’s disease is finding ways to delay the progression of the disease--to in effect extend the life of human memory--instead of waiting for a cure.
With a special sense of urgency, scientists fear that a wave of Alzheimer’s cases will become the great public health menace of the next century. Today’s 4 million victims of Alzheimer’s could become an army of 14 million by the middle of the next century. It will be an era of extraordinary longevity, when 1 in 5 Americans will be over the age of 65. If the onset of the disease can be slowed by five years, the fiscal toll on society, projected at $347 billion annually by 2050, could be trimmed to $200 billion. And the nation would be spared the “pain and suffering that affect patients and their families,” said Dr. Marcelle Morrison-Bogorad, director of neuropsychology of aging at the National Institute on Aging.
Scientists reason that if they can slow down the symptoms--first confusion, then a deepening loss of memory and eventually bed-ridden helplessness--elderly patients will die of other causes before the disease takes hold.
To test this theory, the aging institute next year will recruit thousands of people who are vulnerable to Alzheimer’s for trials of different substances that might slow its progress.
Trials May Lead to New Era
The volunteers will be people who have just begun to show signs of memory loss and confusion, and the hope is that some of the substances tested will halt temporarily their slide down the Alzheimer’s slope. Half the volunteers will get the substances and the other half a placebo, providing scientific evidence about whether such novel compounds as vitamin E or estrogen or even the herbal medicine gingko work alone or in concert with other substances to slow Alzheimer’s.
The trials ultimately could lead to a new era, giving doctors a wealth of more-effective weapons against the dreaded disease. Today, there are only two sanctioned drugs, Cognex and Aricept, to give patients perhaps a year of stability before their thinking processes and memory resume the inevitable decay. The promise of next year’s tests is no less than extending human memory.
Lots of small-scale studies already have given researchers encouragement about vitamin E, anti-inflammatory drugs and other substances. But there have been no full-scale trials to validate scientifically whether these substances really make a difference. With the new study, the population samples will be much larger, and “we will be looking at people who don’t have Alzheimer’s disease yet,” said Morrison-Bogorad. “We need to intervene sooner.”
And in a separate study, the federal government will explore whether estrogen can delay mental deterioration in women over 65. Research on Alzheimer’s will be added to the national Women’s Health Initiative, a long-term exploration of women’s health by a network of university research centers using federal funds.
Meanwhile, drug companies, recognizing a huge multibillion-dollar market, are moving rapidly to develop compounds for Alzheimer’s treatment. At least 17 drugs are in clinical trials or awaiting approval by the Food and Drug Administration. All of them depend on the delay strategy, slowing down the deterioration in people already suffering from the disease. The drug companies, like the government-financed researchers, acknowledge that there is no cure in sight.
Scientists are racing to discover new treatments because the group that falls victim to Alzheimer’s, those over 65, is the fastest-growing segment of the population. During the 1940s and 1950s, polio was the nightmare disease, striking at children, the fastest-growing population group. “We remember the fear, the warnings: ‘Don’t go into a swimming pool; don’t get a chill,’ ” said Dan Perry, executive director of the Alliance for Aging Research, which lobbies for more government spending on Alzheimer’s and other diseases of aging.
For baby boomers and their older brothers and sisters, Alzheimer’s is likely to be the polio of the new century, a fearsome threat to families. Today, the oldest of the boomers worry about their own parents. In the next century, the boomers themselves will be at risk.
But Alzheimer’s is not like polio or other illnesses where an invasive virus can be defeated with a preventive vaccine. Instead, Alzheimer’s is a complex event in which a natural process goes wrong. The brain makes too many amyloid proteins and they become clumped and tangled, blocking the brain cells from sending signals to each other, from carrying messages vital to thinking and memory.
Alzheimer’s may prove to be similar to heart disease and excess cholesterol. Some cholesterol is essential but too much is dangerous.
“There will always be Alzheimer’s disease,” acknowledged Dr. Leon Thal of UC San Diego at a recent aging institute conference here that drew the nation’s top Alzheimer’s experts. “But maybe we can do with amyloids what we do with cholesterol: turn down the excess production. We can turn it down, but we can never turn it off.”
“The major problem is that the brain is absolutely the most complicated organ in the body, and we do not know much about how it functions normally,” said Morrison-Bogorad. Basic biological research has uncovered several genes that cause a predisposition toward developing Alzheimer’s disease. It means increased risk but not the inevitability of becoming a victim. And even among those with one of the genes, there are mysterious variations in the bad luck lottery of developing Alzheimer’s. For example, African Americans with the APOE4 gene are much less likely to develop the disease than Caucasians with the identical gene.
Memory Functions Pose Research Mystery
Another mystery is the way in which different memory functions disappear under the onslaught of Alzheimer’s. Athletic memory skills last a long time. A person can play golf or tennis well into the course of the disease, perhaps long after forgetting what year it is or the name of the president.
For scientists, it makes sense trying to delay the disease because Alzheimer’s is a crisis of old age, a consequence of the great improvements in longevity in this century. There have always been a few people who survived to old age, but this is the first time in human history when great masses of people live well into their 80s and beyond.
At age 65, only 1% or 2% of the population has Alzheimer’s, but prevalence accelerates dramatically with each additional year of life and may reach as high as 50% at age 85, scientists believe.
That’s what makes the postponement strategy so attractive: If you intervene with a treatment at the earliest stage of memory loss and stave off further deterioration for five years, you cut the incidence of the disease by 50%. And for the 76 million baby boomers, born in 1946 through 1964, the biggest generation in American history, timing is everything.
But for those who have the disease now, treatments are sparse and frustrations many.
At the Jewish Home for the Aging in Reseda, Dr. Rick L. Smith, the medical director, uses the drug Aricept as a standard treatment for those with mild to moderate cases. It is effective for up to a year in keeping people from getting worse in their memory and thinking processes. “But inevitably, you are going to continue to decline,” Smith said.
Hoping for better results, Smith also tries other things. He gives his patients vitamin E in high doses. And since many of the patients have been trying gingko biloba, an herbal supplement sold over the counter that is said to improve mental alertness, Dr. Smith lets them keep using it.
Smith’s approach--some of this, some of that--could well become the blueprint for treatments of the future.
“Traditionally, we think of one medicine for one disease, like penicillin for strep throat,” said Dr. Robert Butler, director of the International Longevity Center, a research organization. But with Alzheimer’s disease, “we may wind up with a multiple attack.”
The winning approach could turn out to be an eclectic treatment that uses a variety of drugs and chemicals, predicted Butler, a psychiatrist and pioneer in aging studies, who served as first director of the National Institute on Aging and later as head of the geriatrics department at Mt. Sinai Medical Center in New York.
Exercise Will Play Role
Exercise, physical and mental, also will be part of the armory of weapons deployed against Alzheimer’s, Butler said. Some researchers believe that the runner’s “high,” a feeling of well-being that comes with chemicals produced in the brain after vigorous exercise, could provide a clue to future Alzheimer’s treatments. As a result, some doctors in France have already developed techniques for “brain jogging,” memory exercises.
All these tentative approaches have a single goal: to assure that, for as many people as possible, aging will be a time of life without the disaster of Alzheimer’s disease. Without it, families could be spared the lament of one victim’s spouse: “The loneliest thing in the world is fixing three meals a day for someone who won’t talk to you anymore.”
