Feb. 7, 2003 UCLA and University of Queensland (Australia) neuroscientists using a powerful new imaging analysis technique have created the first three-dimensional video maps showing how Alzheimer's disease systematically engulfs the brains of living patients. The findings appear in the Feb. 1 edition of the peer-reviewed Journal of Neuroscience.
The dramatic time-lapse videos 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 Alzheimer's patients.
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 development of new therapies. Currently, the impact of therapy with cholinergic drugs and antioxidants is typically 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 Paul Thompson, an assistant professor of neurology at the David Geffen School of Medicine at UCLA and the study's chief investigator. "We were stunned to see a spreading wave of tissue loss. Initially confined to memory areas, this loss moved across the brain like a wild fire, 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 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 Alzheimer's 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 Alzheimer's patients and 14 healthy elderly volunteers with MRI brain scans every three months for two years.
Using the new image analysis technique, the researchers found that the Alzheimer's patients 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.
The study's co-authors included Kiralee Hayashi, Michael Hong, David Herman, David Gravano, Stephanie Dittmer, and Arthur Toga 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, Cambridge, UK.
Video sequences, as well as time-lapse movies (MPEGs) and color images are available online at http://www.loni.ucla.edu/~thompson/AD_4D/dynamic.html .
Additional Online resources:
David Geffen School of Medicine at UCLA: http://www.medsch.ucla.edu/
UCLA Department of Neurology: http://neurology.medsch.ucla.edu/
UCLA Laboratory of Neuroimaging: http://www.loni.ucla.edu
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