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Researchers using brain scans to search for hints of Alzheimer's



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Milwaukee Journal Sentinel

(KRT)

MILWAUKEE - Maytee Aspuro's mother was a Milwaukee high school teacher who, at age 59, began showing signs of Alzheimer's disease.

"She was starting to experience memory loss," Aspuro recalled. "They were surprised she still was teaching. But she was a very intelligent woman, and she used her intelligence as a way of coping."

Eventually, the disease won out and at age 62 her mother, Acacia Aspuro, had to leave her teaching job. She died in 1993 at age 69.

So when University of Wisconsin-Madison researchers asked Aspuro if she wanted to take part in a brain imaging study involving middle-aged people whose parents had Alzheimer's, she did not hesitate.

Aspuro, 46, of Madison, was one of 122 people from Wisconsin who underwent functional magnetic resonance imaging, or fMRI, as part of a study designed to find the earliest stages of brain changes that may lead to Alzheimer's disease.

"They are all healthy adults," said lead author Sterling Johnson, an assistant professor of medicine at the University of Wisconsin who also works at the Veterans Affairs Hospital in Madison. "It's just that half of them have parents with Alzheimer's disease."

Having a parent with the disease doubles a person's risk.

It is believed that the brain pathology that leads to Alzheimer's may begin as many as 20 years before symptoms appear in brain regions, such as the hippocampus, which is crucial in forming new memories.

Around the country, researchers are using the latest advances in imaging to peer into brain areas that are first affected by Alzheimer's.

"There is incredible excitement about using imaging," said Michael Wood, general manager of magnetic resonance research collaboration at GE Healthcare Technologies in Waukesha, Wis., one of the leading makers of imaging devices.

Among the most promising approaches are those that look at measuring the volume of the hippocampus, similar to what University of Wisconsin researchers are doing, Wood said.

"It would be an incredible advance if we could link size of the hippocampus with progression of disease instead of subjecting the person to a battery of psychological tests," he said.

However, even if there is a breakthrough in early detection, what good will it do?

At the moment, there are no therapies that can halt the progression of the disease, although there are several promising approaches that now are being tested and others that are expected to begin clinical trials in the near future.

That creates the prospect of doctors having the ability to tell large numbers of people they are in the early stages of a disabling and deadly disease that is incurable.

However, the hope is that as potential new therapies become available, they will be developed more quickly and economically because of the diagnostic advances with imaging, said Neil Buckholtz, a branch chief at the National Institute of Aging, part of the National Institutes of Health.

Clinical trials of new drugs might be done in half the time and at much less expense using imaging, he said.

"Instead of hundreds and hundreds of people (for a clinical trial), we might be able to do it with 50," he said.

The aging institute is funding a large nationwide study that will use imaging and other techniques to monitor Alzheimer's in various stages in 800 people over three years.

For the study, brain imaging will be done every six months on 200 healthy people with no signs of the disease, 400 people with mild cognitive impairment, a memory disorder that often leads to Alzheimer's, and 200 people with early Alzheimer's.

The imaging will be done with either MRI or positron emission tomography, a type of scan that looks at the metabolism of glucose in the brain. Because they have dead or dying brain cells, people with Alzheimer's use glucose at lower levels in certain parts of the brain. Some research suggests that PET can discern lower levels of glucose use before actual symptoms occur.

The University of Wisconsin will be one of the medical centers participating in the study.

It will use both MRI and PET to scan the brains of at least 16 volunteers, said Johnson.

However, Johnson is also developing his own brain imaging approach using a different technology called fMRI, a type of scan that is done when the brain is at work, such as when a person is responding to a question.

It uses radio wave signals to measure brain activity, specifically by looking at differences between oxygenated and non-oxygenated blood flow in the brain. When various areas of the brain are performing mental tasks, they need more oxygenated blood.

For the study, the participants, whose average age was 54, underwent a picture recall test.

Aspuro and the other volunteers wore goggles and were put into the MRI tube. Various pictures, some they had seen earlier and some that they had not, were flashed on the goggles.

Because they had not seen some of pictures, their brains would have to form new memories. If the hippocampus was not working properly because brain cells already were dying, it might show up on the fMRI scans.

And that's what Johnson found.

Anatomically, the brains of the two groups looked the same. And on cognitive tests, the two groups scored the same. But in the volunteers who had a parent with Alzheimer's, there was about 80 percent less activity in the anterior hippocampus.

"We are starting to see brain changes ahead of cognitive changes," Johnson said. "We don't know yet if it predicts that they will go on to get Alzheimer's disease. To do that, we will have to follow them for another 20 years."

For the moment, Johnson's test can only detect meaningful differences between groups of people. For that reason, the test can't predict whether an individual will go on to get the disease.

"I think that is still a few years away," he said.

Aspuro, 46, an information technology portfolio manager with the Wisconsin Department of Revenue, said she knew that taking part in the study would not tell her anything about her Alzheimer's risk.

She said she agreed to be a part of the study for her mother.

Aspuro also is taking part in a couple of other Alzheimer's studies.

"You don't participate in these studies to get information about yourself," she said. "I watched a woman who was brilliant and alive lose that all at a young age, and she was my mom."

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(c) 2005, Milwaukee Journal Sentinel. Distributed by Knight Ridder/Tribune News Service.

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