New technique detects
earliest signs
of Alzheimer's in healthy people
Nov.
30, 2003 - Brain researchers would dearly love to reliably identify
changes in brain structure and metabolism associated with early
Alzheimer's disease -- before symptoms emerge.
Such information
would buy precious time and perhaps permit potential therapies to delay
or even prevent the memory-robbing disease. Now, a new study by NYU
School of Medicine researchers brings this goal one step closer to being
realized.
Using a new
technique to measure the volume of the brain, they were able to identify
healthy individuals who would later develop memory impairment, a symptom
associated with a high risk for future Alzheimer's disease. The study is
published in the December issue of the journal Radiology.
In the small study,
led by Henry Rusinek, Ph.D., Associate Professor of Radiology at NYU
School of Medicine, the researchers used MRI scans and a computational
formula to measure a region of the brain called the medial-temporal lobe
over a period of two years. This area contains the hippocampus and the
entorhinal cortex, key structures allied with learning and memory. The
researchers found that each year, this region of the brain shrank
considerably more in people who developed memory problems compared with
people who didn't. The medial-temporal lobe holds about 30 cubic
centimeters -- the equivalent of one-sixth of a cup -- of brain matter
in each hemisphere of the brain.
"With our
findings, we now know that the normal healthy brain undergoes a
predictable shrinkage that can be used to help recognize Alzheimer's
several years before clinical symptoms emerge," says Dr. Rusinek.
"We believe this is the first MRI study to report these findings in
healthy people, but it is only the first demonstration that extremely
early diagnosis is possible, and the technique still requires additional
work before it is ready for the clinic," he adds.
The technique was
about 90 percent accurate, meaning that it correctly predicted cognitive
decline in nine out of 10 people, and it also correctly identified 90
percent of those whose memories would remain normally for their age.
However, the study
only involved 45 people; future studies need to ascertain whether the
technique would be as accurate in a much larger pool of subjects. In
addition, it remains to be shown whether other neurodegenerative
diseases that affect the aging brain can also be accurately identified
with this technique.
"I believe that
this technique opens an era of early diagnosis of Alzheimer's
disease," says Mony J. de Leon, Ed.D., Professor of Psychiatry at
NYU School of Medicine and one of the co-authors on the new study.
"Now, we want to combine this technique with measurements of
certain Alzheimer-related proteins found in the cerebrospinal fluid, to
get an even more diagnostically specific assessment," says Dr. de
Leon, who is also Director of the Center for Brain Health at the William
and Sylvia Silberstein Institute for Aging and Dementia at NYU and a
research scientist at the Nathan Kline Institute, an affiliate of NYU
School of Medicine, in Orangeburg, N.Y.
Alzheimer's disease
is a progressive illness that kills neurons in the brain, initially
causing memory loss and eventually leading to dementia. It afflicts some
four million older adults in the United States. Perhaps three times as
many individuals suffer early-stage forms of the disease that
incapacitate memory to one degree of another. Currently, the disease can
be diagnosed definitively only after a person dies, by an autopsy
showing certain brain abnormalities.
Previous research by
NYU investigators and others has shown that MRI and PET imaging can
reveal structural and metabolic changes in the brain that appear to
point to early losses in memory and cognitive skills. For example, Dr.
de Leon and his colleagues were the first to demonstrate with MRI scans
that the hippocampus shrinks in people with mild cognitive impairment
(MCI), a form of memory loss that often precedes Alzheimer's.
Despite the promise
of the MRI studies, the hippocampus is notoriously difficult to measure.
Shaped like a sea horse and only about four centimeters long (shorter
than a pinky), the brain structure yields its exact dimensions
unwillingly. The entorhinal cortex is even smaller than the hippocampus,
and it, too, is hard to discern clearly.
Faced with these
challenges, Dr. Rusinek set out to devise a technique that would be more
reliable than currently available methods for measuring atrophy in the
region occupied by the hippocampus and entorhinal cortex. He based his
technique on a mathematical algorithm created by British researchers for
measuring the volume changes of the whole brain, and adapted it to
measure a specific region of the brain: the medial-temporal lobe.
Dr. Rusinek reasoned
that as long as he was measuring the brain area that contained the
hippocampus and the entorhinal cortex, the other structures within his
box were inconsequential. "His technique is like fishing with a
net," says Dr. de Leon. "The position of the fish in the net
doesn't matter. All that matters is that you are using a big enough net
to catch a particular fish."
The new study
followed a group of 45 healthy men and women over the age of 60 for six
years. At the beginning of the study, everyone was within the normal
range on a battery of tests typically used to detect early loss of
memory and other mental deficits. Each person received a baseline MRI
scan, which was repeated two years later.
Thirteen of the
people declined mentally over the course of the study, and six declined
after the second MRI scan. Among those who declined, the rate of atrophy
in the medial-temporal lobe was the most important variable that
distinguished them from the normally aging individuals. The region lost
about 0.7 percent of its volume annually -- an amount smaller than the
size of a pea. While in the normal aging subjects the region shrank by
less than half that volume.
Dr. Rusinek is now
attempting to improve the accuracy of the technique by measuring the
volume of white and gray matter in the medial-temporal lobe and by
improving the spatial resolutions of the MR images. White matter is the
fatty insulation around the long, cable-like axons of neurons; gray
matter contains the bodies of neurons. In a person with Alzheimer's
disease, the gray matter is largely destroyed. In future studies, Dr.
Rusinek expects to find a greater loss of gray matter in people who are
likely to develop the kind of cognitive impairment that precedes
Alzheimer's disease