New Alzheimer's research is making dramatic strides in treating one of the most common - and feared - forms of dementia. The degenerative brain disease strikes one in 10 of those over 65, and almost half of those over 85. Alzheimer's currently affects some 4 million Americans, but experts predict that number could grow to 14 million in the next 50 years unless a cure or preventive treatment is found.

Research is focusing on three main areas:

• What causes the brain to malfunction?
• How can Alzheimer's be treated effectively?
• How can Alzheimer's be diagnosed in its earliest stages?

Causes

Alzheimer's is believed to be caused by abnormal protein deposits in the brain known as amyloids. "We think if we can prevent amyloid deposits in the brain, we can prevent Alzheimer's," says Dr. Scott Turner, assistant professor of neurology at the University of Michigan, Ann Arbor. But therein lies the challenge.

These abnormal clumps in the brain cells of dementia patients were first described by Alois Alzheimer in 1906. But these "plaques and tangles" (amyloids) remain the subject of speculation. "We're still asking, 'What causes these plaques, and what influences their formation?" says Dr. Scott A. Small, Irving assistant professor of neurology at Columbia University's College of Physicians and Surgeons. Are the plaques themselves the cause of brain disfunction, or are the plaques merely a symptom of proteins gone awry?

"Alzheimer's starts in a very small place in the brain at first, and then it spreads," Small explains. Symptoms are subtle at first - memory lapses, mild confusion - but then progress to the point where individuals have difficulty with familiar tasks, like cooking, balancing a checkbook or speaking coherently. Advanced Alzheimer's is marked by personality shifts, confusion, disorientation and an inability to handle even rudimentary tasks.

A dramatic breakthrough occurred in 1996 with the production of genetically modified mice that can mimic Alzheimer's features like amyloids. The advance allowed researchers to investigate the protein tangles that slowly strangle the Alzheimer's brain.

"Once you develop these animal models of Alzheimer's, then you can start testing various treatments in mice, and then seeing if they work in humans," Small says. "That's truly one of the most exciting developments we've seen."

Treatment

Researchers are testing several potential treatments to delay the progression of Alzheimer's. These include Vitamin E, estrogen, and the drug Aricept. A class of drugs called "statins," used to control cholesterol, also shows promise in delaying or preventing Alzheimer's, Turner says.

Other researchers are investigating whether anti-inflammatory drugs, like ibuprofin, may affect inflammation associated with Alzheimer's. Still others are probing whether small strokes, hormonal imbalances, or even vitamin deficiencies might accelerate Alzheimer's. Another approach targets various enzymes thought to produce the amyloid proteins, in hopes of blocking the plaque-forming mechanism. "This is the first small step toward real treatments down the road," Small says.

Perhaps the most tantalizing prospect involves an Alzheimer's vaccine, much like the common flu shot, where patients are injected with an amyloid protein.

"It's as incredibly simple as it is elegant, if it works," Small says. "We simply allow the body to generate an immune response to the abnormal amyloid proteins. Then your body develops antibodies that act to either prevent plaques from forming, or even removing them. The data in mice, I must say, are absolutely astounding. We're now waiting to see if that's going to pan out in humans."

Unfortunately, an immunization trial with Alzheimer's patients was halted in January after 14 of the 375 participants developed encephalitis, Turner says.

Diagnosis

Still, even if a cure for Alzheimer's did exist, its side effects would almost certainly preclude giving it to everyone, Small suggests. Instead, it would have to be targeted to individuals most at risk of Alzheimer's. And that's the catch.

"Even if we had this fantasy drug, we wouldn't know who to give it to," Small says. The key is improving our ability to diagnose Alzheimer's at its earliest stages.

"We're actually pretty good at diagnosing Alzheimer's when someone has profound dementia," Small says. "But we're terrible at making the diagnosis when someone has the first inklings of memory decline."

The three general approaches to diagnose Alzheimer's are:

• Neuropsychological tests, usually involving memory tests (see sample)
• Blood tests that measure amyloid protein levels
• Imaging technologies such as MRIs that allow researchers to see disease-related changes in the brain's structure or functions.

Small is using imaging technology to pinpoint the subtle, but telltale changes in the brain in the early stages of Alzheimer's. Other researchers are using imaging to examine the structure of the amyloids themselves for clues to the disease's development.

"I think we've made enormous progress in the last 15 years," Turner says. While a cure remains elusive, promising new therapies are offering hope to millions.