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Alzheimer’s--Parts of Puzzle Are Falling In

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Times Medical Writer

Scientists investigating Alzheimer’s disease, the most relentless of all causes of senility, are growing closer to understanding the roles played by a number of brain chemicals in the occurrence of symptoms that typify the devastating illness.

Only recently researchers believed that Alzheimer’s resulted from a deficiency of a single brain chemical and if the chemical could be replaced, the progressive deterioration of mental functions that trouble Alzheimer’s patients might be arrested.

But research presented at a Los Angeles conference last week by leading authorities indicated that a number of other brain chemicals may also play important roles in producing the disease. All of these chemicals are called neurotransmitters.

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While the picture is still far from clear, the recent reports “provide a crucial beginning for piecing together the Alzheimer’s disease puzzle,” according to Dr. Zaven Khachaturian of the National Institute on Aging, who was an observer at the conference sponsored by the John Douglas French Foundation for Alzheimer’s Disease.

Lack of Brain Chemical

Scientists first suspected lack of the brain chemical choline acetylcholinesterase as the cause of Alzheimer’s. Since the late 1970s, researchers have tried several different ways to give patients extra choline in attempts to restore the memory loss and other impaired mental functions that go along with the disease.

But to date, no such treatment has yielded better than short-term improvements in some, but not all, of the multiple mental dysfunctions that patients experience.

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In a report on patients who have received infusions of a choline-promoting drug directly into their brains, Dr. Robert Harbaugh of Dartmouth-Hitchcock Medical Center in Hanover, N.H., said that a preliminary review of the results on four of 10 patients in the study showed short-term improvements in a test that measures orientation, memory and language.

But the method of introducing the drug, which involves implanting a pump in the abdomen along with tiny tubes that move the drug into the brain, carries substantial risks, according to Dr. Stephen Read, a UCLA physician who participated in the program.

For example, Read said, of five patients treated with the method at the Brentwood Veteran’s Hospital, three had seizures, one developed meningitis and the fifth had a brain hemorrhage.

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Moreover, scientists now generally agree that Alzheimer’s is not due to a deficiency of just one neurotransmitter, although they say there is ample reason to believe that a lack of choline does seem to be important in causing some of the problems.

According to Khachaturian, a growing number of reports indicate that perhaps the deficiencies of choline and other neurotransmitters may be the result of still more basic changes that take place in the brain.

Glucose, a sugar, is the brain’s energy source for everything that it does, including making neurotransmitters, which are chemicals that carry messages along nerve pathways. Glucose and another necessary ingredient, oxygen, are carried to brain cells through miles of tiny blood vessels in the brain.

Amyloid Theory

Anything that damages the flow of glucose and oxygen, Khachaturian said, will impair the manufacture of neurotransmitters. One theory, set forth by Dr. George Glenner of UC San Diego, about what happens in Alzheimer’s involves a compound called amyloid. Almost uniquely among humans, amyloid is found in the brains of Alzheimer’s patients. Glenner believes that amyloid triggers changes in blood vessels which, over a long period of time, slowly starve nerve cells, causing them to gradually stop making neurotransmitters.

“This is an exciting idea,” Khachaturian said. It means, he said, that it may be possible to deal with the underlying problem that explains why neurotransmitters become deficient, rather than the secondary one of neurotransmitter depletion.

One factor that helps give the theory support is that amyloid is also found in the brains of Down’s syndrome patients who are over 40. Down’s is a form of mental retardation. The brains of Down’s patients over 40 also have the same nerve cell abnormality--tangles of nerve fiber called senile plaques--that are found in Alzheimer’s patients.

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But it became clear as the conference progressed that the 10 years in which scientists have seriously explored Alzheimer’s disease has not been long enough to integrate all that has been learned.

Lack of Reliable Test

For example, although the symptoms of senility of up to 3 million people may be due to Alzheimer’s, doctors still lack a reliable diagnostic test to differentiate Alzheimer’s patients from those with other causes of senility, said Dr. D. Frank Benson, a UCLA professor of neurology.

“Nobody in this room can tell who has Alzheimer’s,” Benson said. “We all have our ideas but there is no agreement on them. We don’t know who has Alzheimer’s.”

A lead for a possible future diagnostic test was reported by Jennifer Buchwald Ph.D., an electrophysiologist at UCLA’s Brain Research Institute, who has discovered what may be a brain-wave characteristic that is unique for Alzheimer’s patients.

But, researchers pointed out, more work must first be done to make sure that the brain-wave characteristic does not appear also in patients with other types of brain disease.

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