Structural
Magnetic Resonance Imaging (MRI) could become an important tool for
characterizing and diagnosing Alzheimer's disease (AD) in its very
early stages, well before clinical signs appear, according to a new
study by researchers in Boston. The study, which measured the volume
of specific regions of the brain affected early in the disease process,
is a significant step toward ultimately predicting who may be at risk
for AD and who might benefit from drug treatments that could prevent
the disease or slow its progression.
The
research, conducted by Marilyn Albert, Ph.D., and her colleagues at
Massachusetts General Hospital (MGH) and Harvard Medical School, with
collaborators at Brandeis and Boston Universities and Brigham &
Women's Hospital, is reported in the April 2000 issue of the Annals
of Neurology.
"This
study is important for a couple of reasons," says Neil Buckholtz,
Ph.D., chief of the Dementias of Aging Branch of the Neuroscience
and Neuropsychology of Aging Program at the National Institute on
Aging (NIA), which funded the study. "First, it offers evidence
establishing the involvement of specific areas of the brain in the
underlying early pathology of AD. It also suggests that, by zeroing
in on these areas, we may be able to use already available imaging
techniques to better identify people at greatest risk and those for
whom early treatment could make a difference."
The
study was designed to see whether people in the "preclinical"
phase of AD -- people with mild memory impairments who would develop
AD at the end of the study -- could be identified accurately, in advance
of showing outward signs of the disease. At the outset of the study,
the 119 participants were divided into two groups -- normal and those
with mild memory difficulties -- and each received a baseline MRI
scan. Over 3 years, the participants were followed to determine who
developed AD, which was diagnosed by a standard medical evaluation.
Researchers then went back to the MRIs that had been taken 3 years
earlier to see if the scans could prove useful in predicting who would
develop AD. The average age of study participants was the early 70s.
Previous
research had indicated that measurements of hippocampal volume could
identify some cases of AD before a patient met clinical criteria for
dementia. But the Boston researchers were seeking to improve accuracy
by honing in on select areas of the brain involved at an earlier stage
in the disease process. Albert and colleagues looked at differences
in volume in a number of areas, focusing on the entorhinal cortex
and the banks of the superior temporal sulcus, both involved in memory,
and the anterior cingulate, which affects "executive" functions
such as organizing, planning, and switching back and forth among tasks
and ideas. Recent studies have shown several of these areas to be
affected by a significant loss of neurons early in the AD process.
The
researchers found that they could identify people who would develop
AD over time based on measurements of these brain regions. The MRIs
were 100 percent accurate in discriminating between the participants
who were normal and those from a third group looked at by Albert's
team who already had mild AD. They were 93 percent accurate in discriminating
between participants who were normal and those who initially had memory
impairments and ultimately developed AD; the entorhinal cortex in
the case of the people "converting" to AD had about 37 percent
less volume than the entorhinal cortex of those who remained normal,
probably reflecting a loss of brain cells. Other comparisons showed
a relatively high accuracy rate as well, although it was more difficult
to distinguish the people who continued to have memory problems but
did not progress to AD from those who eventually converted to AD.
Albert
emphasizes the importance of developing such diagnostic techniques
at this time, in concert with the development and testing of dozens
of new drugs it is hoped will prevent or slow the progression of AD.
"Effective treatments for Alzheimer's disease are likely to be
ready over the next decade or so," she notes. "In the not
too distant future, we may be able to use MRI, in combination with
other measures, to identify people at highest risk who can be effectively
treated as these new therapies come along." Albert says that
these types of measurements might be useful in monitoring response
to treatments as well.
The
researchers caution, however, that their MRI technique will need to
be further refined and validated before it can be used in everyday
practice by neurologists and MRI technicians. Albert points to the
study's value in getting scientists on the "right track"
about what to measure. But, she says, more research in several areas
will need to be done, including follow-up of patients over a longer
period of time to more precisely gauge the predictive value of the
MRIs. Also, the researchers would like to look at functional MRIs
and other imaging techniques to see if accuracy can be improved.
Generally,
interest is intensifying in the use of imaging for study and diagnosis
of AD. According to Buckholtz, serial MRIs will be used to follow
participants in an NIA-sponsored trial testing the usefulness of vitamin
E and donepezil to stop or slow the conversion of people with mild
cognitive impairment, or MCI, to Alzheimer's disease.
The
NIA is one of 25 institutes and centers at the National Institutes
of Health. It leads the Federal effort to study Alzheimer's disease,
supporting basic, clinical, epidemiological, and social research on
aging and the special needs of older people and their families.
For
specific information on Alzheimer's disease and clinical trials in
progress, the public can contact the NIA's Alzheimer's Disease Education
and Referral (ADEAR) Center at 1-800-438-4380 or adear@alzheimers.org.
You can visit the ADEAR website at http://www.alzheimers.org.
