UCLA
Neuroscientists Map How Alzheimer’s Disease Systematically
and Sequentially Engulfs the Brain
Date: February 6, 2003
Contact: Dan Page ( dpage@support.ucla.edu
)
Phone: 310-794-2265
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 www.loni.ucla.edu/~thompson/AD_4D/dynamic.html.
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