TO KNOW YOUR OWN FATE

By J. MADELEINE NASH

For most people, a momentary lapse of memory seems no more serious than getting the hiccups. But Los Angeles attorney Sally Weinper shudders every time she misplaces a file or draws a mental blank on a fine point of law. Weinper, 54, has already watched three aunts die of Alzheimer's disease. And now her mother is suffering from this terrifying illness that slowly destroys the brain and mind. "Because I know I'm at risk," Weinper says, "this insidious threat runs through every day of my life. To be trapped in your body but not be able to formulate words or recognize your own children, to be isolated from your friends, to give up your dignity ... to me it seems like hell on earth."

Until recently, medical researchers could offer sympathy and little else to the 4 million Alzheimer's patients in the U.S. Not only did physicians have few ideas about the cause of the disease, but they even had trouble diagnosing it. Now that situation is changing. In the future, suggests a tantalizing study reported last week in the Journal of the American Medical Association, doctors may be able to identify individuals in the earliest stages of the illness--years or even decades before any noticeable decline in intellectual ability.

But such a test could create a dilemma of a different sort: do people really want to know that Alzheimer's lies in their future when medicine can offer no cure? "If there's no way of controlling what happens to you," observes University of Iowa neurologist Dr. Antonio Damasio, "then it's unclear that early diagnosis provides an advantage. What you're probably going to do is worry yourself sick."

The possibility of early diagnosis arises from advanced brain-mapping technology and new insights into the genetics of Alzheimer's. In recent years, researchers have learned that the disease is linked to the presence of a gene called Apo-E4. But the gene does not always trigger the illness; people with one copy of the gene have perhaps a 50% chance of getting Alzheimer's, and for those with two copies the likelihood rises to about 90% by age 80. In no cases can geneticists reliably predict at what age the disease will start.

The research published last week offers hope for a more precise test. Led by Dr. Gary Small, a UCLA psychiatrist, the study focused on a small group of middle-aged volunteers, all of whom had relatives with Alzheimer's and who complained of mild memory problems themselves. First the researchers drew blood samples to test for the presence of the Apo-E4 gene. Then they used a PET scanner (positron emission tomography) to record each patient's pattern of brain activity. After a computer sifted through the data, a striking correlation emerged. A group of 12 individuals who had inherited Apo-E4 showed diminished activity, particularly in the parietal region of the brain--a region that is dramatically impaired by Alzheimer's--when compared with other patients who did not have the gene. If those results are supported by larger studies, and if brain-scanning techniques are refined, then doctors may be able to test for early-stage Alzheimer's within a few years.

But what about a treatment? So far, just a single drug--tacrine--is approved for use against Alzheimer's. Tacrine offers only a slight, temporary easing of symptoms. On the horizon, however, are remedies that may prove more promising. There is evidence, for instance, that estrogen-replacement therapy for post-menopausal women may protect brain cells from the disease. Likewise, anti-inflammatory drugs used to allay diseases caused by out-of-control immune systems--such as rheumatoid arthritis and lupus--may be able to slow the progression of Alzheimer's. Most encouraging of all, Duke University researchers recently joined forces with the pharmaceutical giant Glaxo to design a drug that mimics the beneficial effects of another version of the Apo-E4 gene. Such therapies have the best chance of being effective, researchers agree, if they are given in the early stages of the disease.

That may be reason enough for potential patients to get tested and know where they stand. Not so long ago, observes Dr. Mark Siegler, a University of Chicago medical ethicist, many doctors concealed a cancer diagnosis from patients, fearing that their psychological pain would be unbearable. That practice ended, however, as effective treatments started to arrive. "Maybe," says Siegler, "the 1990s will be for Alzheimer's disease what the 1970s were for cancer, a time of rising hope and an expectation that a diagnosis is not invariably terminal."

Besides, says Siegler, there is often great value to knowing one's fate even when nothing can be done to escape it. Consider the example of Sally Weinper. "I'm taking stock of my life," she says. "While I'm still in a cogent frame of mind, I'd like to spend more time with my family and friends. I want to smell the roses now because I may not be able to recognize them later on."

--With reporting by Lawrence Mondi/New York