Brain Scan May Spot Alzheimer's Progression

In the future, new technologies could identify who's at risk, researchers say

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By Steven Reinberg
HealthDay Reporter

TUESDAY, Nov. 15, 2005 (HealthDay News) -- Newly developed brain-scanning technology may help identify how Alzheimer's disease progresses and who is likely to get the disease, two new studies suggest.

Both were to be presented Tuesday at the Society for Neuroscience annual meeting, in Washington, D.C.

In the first study, researchers presented preliminary results of a new technique that uses a radioactive marker, called Pittsburgh Compound-B (PIB), plus PET scans to track the progression of characteristic protein deposits in the brains of Alzheimer's patients.

Since PIB binds to these beta-amyloid deposits in the brain, researchers can see plaque build-up and how it changes over time.

"This technology allows us for the first time to look at the changes in the brains of Alzheimer's patients that we could only see at autopsy before," said lead researcher Dr. William E. Klunk, an associate professor of psychiatry at the University of Pittsburgh School of Medicine and co-inventor of the technique.

In the study, Klunk's team used the technique to study the brains of five Alzheimer's patients, five normal patients and five patients with another type of dementia, called Lewy Body dementia.

Researchers were able to use this technique to watch changes in the brain, Klunk said. "We can see where these beta-amyloid deposits start, in what parts of the brain they start, and how they progress over time."

The discovery could enable researchers to understand more about the disease while aiding in drug development. "We first need to know what the natural history of the amyloid changes in the Alzheimer's brain is," Klunk said. "Once we know what it normally is, then we can test drugs and pick out the ones that are best at changing that."

Klunk cautioned that this work is still at an early stage of development. "This isn't something that people can go to their doctor and have done," he said. "That will be a number of years away."

In the second study, researchers used a combination of PIB/PET scans and cerebrospinal fluid (CSF) analysis to find markers that can predict Alzheimer's disease.

"Our goal is to identify biomarkers, to be able to diagnose people early in the disease stage, hopefully, even before cognitive symptoms start," said lead researcher Anne Fagan Niven, a research associate professor of neurology at Washington University School of Medicine in St. Louis.

In their study, the first of its kind in humans, Fagen and her colleagues studied 24 people, some diagnosed with very mild or mild Alzheimer's disease and others who were cognitively normal. Participants underwent a spinal tap to collect CSF and also had PIB/PET scans.

Most people didn't have amyloid plaques in their brains, but some did, the St. Louis team found. "Of all the people who had positive PIB finding, every single one of them also had reduced levels of a peptide called amyloid beta 42 (A-beta 42) in their CSF," Fagan said. A-beta 42 is the principal ingredient of the brain plaques.

"To our surprise, three of the people that were PIB-positive and had low A-beta 42 levels were clinically normal," Fagan said.

Fagan believes the presence of amyloid plaques and low A-beta 42 levels in these patients may be a signal for preclinical Alzheimer's disease. "Of course we can't prove that," she said. "We need to follow them over time to see if they are at risk for dementia."

"In my dreams, I see 10 to 20 years from now, people who are 50 to 55 years old will get a cognitive evaluation, a PIB scan followed by a CSF test, combined with genetic markers," Fagan said. "And the doctor will be able to tell people on an individual basis their risk for developing Alzheimer's disease."

Fagan believes by that time there will be ways to effectively treat or slow Alzheimer's.

One expert believes that both studies are important, but still experimental.

These are small studies, noted Mony de Leon, a professor of psychiatry and director of the Center for Brain Health at New York University School of Medicine. "Will they be useful? Maybe."

The predictive value of the CFS-based method in identifying early Alzheimer's has yet to be shown, de Leon said. "That projection forward needs to be done," he said.

"The first evidence is encouraging," for both studies, de Leon stressed, "but additional evidence is needed."

All of this research is a step in the right direction, however.

"Researchers are really zoning in on some of the markers of Alzheimer's disease, making a future diagnostic test even more of a likelihood than it was just a few months ago," de Leon said.

Encouraging news was also reported Tuesday by drug company Myriad Genetics Inc., which said a Phase II clinical trial of its drug Flurizan resulted in a 33 percent improvement in cognition in patients with mild forms of Alzheimer's disease.

Results of the six-month study were presented at the Neuroscience 2005 meeting in Washington, D.C. The findings were presented by Dr. Sandra E. Black, a professor of neurology at the University of Toronto and lead investigator in Canada for the phase II trial of Flurizan.

More information

For more on Alzheimer's disease, head to the Alzheimer's Association

SOURCES: William E. Klunk, M.D., Ph.D., associate professor, psychiatry, University of Pittsburgh School of Medicine; Anne Fagan Nevin, Ph.D., research associate professor of neurology, Washington University School of Medicine, St. Louis; Mony de Leon, Ph.D., professor, psychiatry and director, Center for Brain Health, New York University School of Medicine, New York City; Nov. 15, 2005, presentations, Society for Neuroscience annual meeting, Washington, D.C.

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