Despite Research Gains, Disease Puzzles Scientists

‘Although we don’t know much, it’s a lot compared to what we didn’t know 10 or 15 years ago.’--Dr. David Drachman

Dr. David Drachman always includes a caveat when discussing Alzheimer’s disease.

“This is a tough disease,” said Drachman, head of neurology at the University of Massachusetts Medical Center and chairman of the scientific advisory committee for the Alzheimer’s Disease and Related Disorders Assn.

“I believe a treatment may be available for the next generation,” he said. “But it is probably true that people who are already afflicted with Alzheimer’s disease will not benefit from anything we’re working on now.”

“Then again,” he always added, “I would be pleasantly surprised if a treatment came along tomorrow.”

Such is the uncertain knowledge of a disease that affects about 2.5 million Americans, but has no known cause, no diagnostic test, no proven treatment and, as yet, no cure. The disease itself has been known for 80 years, but most serious research on it dates back only a decade or so.

In recent years, however, federal funding for Alzheimer’s research has increased fivefold to about $65 million annually. The Alzheimer’s association, which added $2.2 million to that total, believes $500 million a year is a more reasonable research goal for a debilitating, irreversible illness that will affect 5 million Americans by the year 2000.

But the current research is bearing fruit, Drachman said.

“Although we don’t know much, it’s a lot compared to what we didn’t know 10 or 15 years ago,” he said.

The Disease

Alzheimer’s disease is a deteriorating neurological illness in which the victim gradually but irreversibly loses control of thought and memory. Victims usually begin with difficulty remembering simple things. In later stages, they forget the names of loved ones, and eventually they regress to an infant-like state, requiring constant care. They can become violent.

First described in 1906 by German physician Alois Alzheimer, the disease is still technically defined by the strange tangles of nerve fibers and abnormal deposits called plaques found in the brains of demented elderly patients.

As such, Alzheimer’s disease can only be positively diagnosed on autopsy, though Drachman says doctors can correctly identify Alzheimer’s cases 85% to 90% of the time using behavioral tests, brain scans and process of elimination.

Strokes and some drugs can also cause disorientation and mental lapses that mimic Alzheimer’s, he says. Sometimes changing a medication dosage or formulation can relieve the symptoms.

Scientists believe the degeneration of brain cells in Alzheimer’s victims is directly caused by a lack of choline acetyltransferase, an enzyme necessary to make the neurotransmitters that allow brain and nerve cells to communicate.

Researchers at the the Albert Einstein College of Medicine last year announced they had isolated a protein, called Alz-50, that does not occur in normal brains or in brain tissue of patients suffering from other neurological disorders. They hope this knowledge will lead to a diagnostic test for the disease.

The Cause

There are a multitude of theories about the cause of Alzheimer’s disease, most of which have some merit but none of which has been proven, Drachman says.

Most promising is the discovery that some Alzheimer’s victims have defective genetic material on their 21st chromosome, the same set of genes implicated in Down’s syndrome. Researchers think this may help explain why Alzheimer’s disease tends to run in families.

But Drachman stressed only about 5% of patients appear to have a dominantly inherited form of Alzheimer’s, and that it is not likely that a genetic defect is the disease’s sole cause.

“However, if we can isolate (the genetic defect) and determine how it expresses itself, that may lead us to an understanding of the illness that will open the way for effective treatments,” he said.

Evidence is much less convincing for other reputed causes of Alzheimer’s.

“So far, there isn’t any clear evidence that aluminum causes the disease, or that a slow virus causes it,” he says. “There’s also been some suggestion of head trauma, and the evidence is not clear there either.”

Treatments

Over the past few years, several drugs have been touted as possible treatments for Alzheimer’s disease, but all have fallen far short of expectations.

Nevertheless, considerable excitement has been generated by the drug tetrahydroaminoacridine (THA), which appears to have improved symptoms in a small group of patients. In August, the National Institute on Aging embarked on a $1.9-million, two-year trial of the drug, which will evaluate 300 patients at 17 research centers.

THA inhibits the breakdown of the neurotransmitter lacking in the brains of Alzheimer’s patients, and thus researchers believe it may relieve some of the memory loss and cognitive impairment seen with the disease. But the drug does not reverse the deterioration process itself, Drachman emphasized.

“No one claims this is a cure,” he says, “But it is the best hope for treatment we have right now. To say any more would be premature.”