Photo/Courtesy UCLA

Using a powerful new imaging analysis technique, neuroscientists have created the first 3-D video maps showing how Alzheimer's disease systematically engulfs the brains of patients (Journal of Neuroscience, Feb. 1, 2003).

The dramatic time-lapse videos, made by researchers at the University of California, Los Angeles (UCLA) and the University of Queensland, in Australia, show the sequential destruction of brain areas that control memory function, then emotion and inhibition, and finally sensation. They also show how the disease spares small brain regions that control vision and other functions that remain intact in patients with Alzheimer's.

The analysis technique, which detects very fine changes in magnetic resonance imaging (MRI) brain scans, offers doctors and researchers a powerful new tool that could speed diagnosis and intervention and the development of new therapies. Currently, the impact of therapy with cholinergic drugs and antioxidants typically is assessed only with cognitive tests; the physical spread of the disease can be evaluated only in autopsy studies.

"For the first time you can see Alzheimer's disease progressing in living patients," said chief investigator Paul Thompson, PhD, an assistant professor of neurology at the David Geffen School of Medicine at UCLA. "We were stunned to see a spreading wave of tissue loss. Initially confined to memory areas, this loss moved across the brain like a wildfire, destroying more and more tissue as the disease progressed."

This type of imaging will allow doctors and researchers to pinpoint where and how fast the disease is spreading, said Dr. Thompson, a researcher at the UCLA Laboratory of Neuro Imaging. "We will urgently apply this method to reveal how drugs and vaccines combat the wave of brain damage caused by Alzheimer's disease."

Alzheimer's afflicts 10 percent of people older than 65. Physicians know that brain lesions, called amyloid plaques and tangles, accumulate in patients' brains, causing memory loss, disorientation, and declining ability to cope with everyday life as brain cells die.

In order to track this cell death, the research team scanned 12 patients with Alzheimer's and 14 healthy elderly volunteers with MRI brain scans every three months for two years. Using the new image analysis technique, they found that the patients with Alzheimer's lost an average of 5.3 percent of their gray matter per year. Brain cells were purged even faster in some brain regions, with patients losing up to 10 percent in memory regions each year. In contrast, healthy elderly volunteers lost only 0.9 percent of their brain tissue annually.

The time-lapse video based on these scans revealed that the leading edge of cell loss moved forward like a burning frontier. As patients' symptoms worsened, the wave of cell loss hit frontal and central brain regions. These brain areas control patients' inhibitions and emotional states. After two years the disease had engulfed virtually the entire brain.

The study was supported by the National Library of Medicine, the National Center for Research Resources, by a Human Brain Project Grant from the National Institutes of Health, and by GlaxoSmithKline Pharmaceuticals UK.

Co-authors included Kiralee Hayashi, Michael Hong, David Herman, David Gravano, Stephanie Dittmer and Arthur Toga, all of UCLA; Greig de Zubicaray, Andrew Janke, Stephen Rose and David Doddrell, of the University of Queensland Center for Magnetic Resonance, Australia; and James Semple, of GlaxoSmithKline Pharmaceuticals PLC and Addenbrooke's Hospital in Cambridge, United Kingdom.

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