Closer to a Cure for Alzheimer's

In the 10 years since Ronald Reagan told the world that he was in the early stages of the Alzheimer's disease that would "lead me into the sunset of my life," prospects for treating others have brightened significantly.

Indeed, the late president's public acknowledgment of the disease—and Nancy Reagan's clarion calls for stepping up Alzheimer's research—put the spotlight on the cruel, mind-wasting illness that afflicts 4.5 million Americans.

The Reagans' candor erased "the last vestiges of stigma" about the disease, says Stephen McConnell, a vice president of the Chicago-based Alzheimer's Association, and helped boost funding for research. Federal outlays to the National Institutes of Health climbed from $298 million in 1994 to $680 million this year.

While the cause remains a mystery and a cure elusive, the pace of research has accelerated in the last decade, yielding a wealth of new information that may lead to better treatments.

Case in point: Scientists at Northwestern University recently discovered a specific link between the gunky plaques of beta-amyloid protein and the abnormal, stringy tangles of protein that are both found in brains damaged by Alzheimer's.

"If you stopped amyloid production or reversed it, could you stop further formation of tangles? That's the $64,000 question," says neurologist Steven T. DeKosky, director of the Alzheimer's Disease Research Center at the University of Pittsburgh Medical Center.

Scientists are also venturing out beyond plaques and tangles in new directions for clues to the genesis of Alzheimer's. They are exploring many approaches to slow or stop the disease—from genetic manipulation and drugs to vitamins and mind and body exercise.

With the aging of 78 million baby boomers, new strategies are coming none too soon. Without preventive measures or a cure, the number of Americans with Alzheimer's could rise to 7.7 million in 2030 and to 13 to 16 million by 2050.

"The growth in this disease is going to be much higher than we thought," McConnell says, because of increasing longevity among the 85-plus population.

Scientists hope the payoff of intensive research will prove those estimates wrong. "In the last six years, there's been an explosion of interest and an explosion of knowledge," says Marcelle Morrison-Bogorad, associate director of the Neuroscience and Neuropsychology of Aging Program at the National Institute on Aging. The fast-paced discovery of the mechanisms in the brain that contribute to Alzheimer's—and that could be blocked with new therapies—is "amazingly hopeful."

DeKosky agrees. "Most of the avenues Alzheimer's research is going down weren't even conceived of 10 or 15 years ago," he says. "Now there is a host of things that are either in trial or speculated about for the future."

MEDICATIONS THE MAINSTAY

The long war on Alzheimer's—an ultimately fatal disease that destroys brain cells and robs a person of memory and reasoning powers—has often been disheartening, with long-awaited "breakthroughs" less helpful than anticipated.

Medications for Alzheimer's, for example, thus far have had mostly modest results. A class of drugs that includes Aricept, Exelon and Reminyl was rolled out beginning in 1996 amid high hopes that they would slow memory loss in the disease's early and middle stages. But the drugs have proved to be limited in their effectiveness.

Last October the U.S. Food and Drug Administration approved Namenda (memantine), the first drug developed for people with advanced Alzheimer's. It blunts the brain chemical glutamate, which can accumulate abnormally and kill brain cells.

Despite some disappointments, medications remain a crucial area for research, with several drugs under study. Two pharmaceutical companies are collaborating on tests of beta-amyloid blockers for safety in humans. The Irish drugmaker Elan Corp. has resumed work on a vaccine to halt beta-amyloid growth after stopping work in 2002 on another vaccine that had caused inflammation in patients.

It's also possible that some drugs used for other medical problems may help fight Alzheimer's. Research indicates, for instance, that people with circulatory problems stemming from high cholesterol and high blood pressure are at increased risk for Alzheimer's as well as for heart attack and stroke. "They frequently overlap," DeKosky says.

Several studies suggest that statins, drugs to lower cholesterol, may help prevent Alzheimer's. One study found a 70 percent lower risk of dementia in 1,300 British patients taking statins than those with normal cholesterol or those not taking cholesterol-lowering drugs.

The National Institute on Aging is funding statin research to see if simvastatin (Zocor) can slow the rate of Alzheimer's progress.

The well-known Nun Study on aging that started with 678 Roman Catholic sisters in 1986 found that a history of small strokes increased the chance of Alzheimer's, says study director David Snowdon, professor of neurology at the University of Kentucky's Sanders-Brown Center on Aging.

The jury is still out on whether anti-inflammatories such as ibuprofen and aspirin can help prevent development of the disease. Research to date indicates they don't help those who already have Alzheimer's.

IT'S IN THE GENES …

Another area ripe for exploration is gene therapy. Scientist have already found some genes that are tied to Alzheimer's disease and suspect there are others.

In a recent study Mark H. Tuszynski, a neurologist at the University of California, San Diego, injected the brains of eight early-stage Alzheimer's patients with their own skin cells, which had been genetically engineered to produce nerve growth factor, a chemical that boosts repair and regeneration of the brain's nerve cells. Preliminary results, which were released in April, demonstrated that the experimental technique was safe and provided some benefit.

… OR MAYBE IN YOUR DIET

Some research suggests that certain foods and dietary supplements may lower the risk of Alzheimer's, among them:

• Vitamin supplements E and C. A study in the Archives of Neurology reported that taking these two antioxidants may help protect brain cells from damage.
• Fish. The Archives also reported that a study of people who ate fish once a week or more had a 60 percent lower risk for Alzheimer's than those who rarely or never ate fish.
• Folic acid. High blood levels of the amino acid homocysteine nearly double the risk for Alzheimer's, according to research reported in the New England Journal of Medicine. Folates and vitamins B-6 and B-12 appear to reduce homocysteine.
• Huperzine. Researchers at the National Institute on Aging are studying this plant-derived supplement that's used in traditional Chinese medicine for fever and other conditions. There's some evidence huperzine could help slow progress in early-stage Alzheimer's.

CALLS FOR STEM CELL RESEARCH

Some experts believe that embryonic stem cell therapy to replace damaged nerve cells in the brain is the best hope for defeating Alzheimer's.

The Bush administration has restricted the development of stem cells. Recently Nancy Reagan has spoken forcefully in support of embryonic stem cell research, and on June 4, the day before the former president died, 58 U.S. senators wrote to President Bush asking him to relax restrictions on such research. In May a bipartisan group of 200 House members wrote a similar letter to Bush.

USE YOUR HEAD

Finally, studies continue to suggest that rigorously engaging your mind throughout life can help prevent Alzheimer's. A long-term study of older adults reported in the New England Journal of Medicine showed that five activities in particular appear to help: reading, playing cards, playing board games, doing crossword puzzles and playing a musical instrument.

In the Nun Study, all the women are or were teachers, and some stay mentally active well into their 90s. Sister Esther Boor, for example, earned her master's degree in theology at age 71 and did not stop teaching until age 97.

Mental and physical activity appear to boost the release of substances in the brain that may help repair damaged tissue, says Nun Study director Snowdon. But "if you have to choose between doing the New York Times crossword puzzle and going for a walk," he says, "put your shoes on and get out the door."

Peggy Eastman writes on health issues for several national magazines.