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DURHAM, N.C. -- Duke University Medical Center researchers
have used imaging technology to identify a new marker that may
help identify those at greatest risk for cognitive decline and
the development of Alzheimer's disease.

The study focused on people with mild cognitive impairment
(MCI), a condition that affects an estimated four to five
million individuals in the United States. People with MCI are
at increased risk for developing Alzheimer's disease in the
future and approximately 30-50 percent of MCI subjects will
develop Alzheimer's if followed over a three- to five-year
period.

Duke researchers used functional magnetic resonance imaging,
also known as fMRI, on people with MCI to track regions of the
brain that become active or inactive when participating in
tasks that involve memory. They then followed these individuals
over time to document progression to Alzheimer's.

"A single baseline fMRI measure of deactivation could help
predict which individuals will convert to Alzheimer's over the
next several years," said the study's lead author, Jeffrey R.
Petrella, M.D. "On the other hand, the fMRI scans of MCI
subjects who did not convert looked more like those of healthy
normal people, and could therefore be reassuring," said
Petrella, who is director of the Alzheimer's Imaging Research
Laboratory and associate professor of radiology at Duke.

The results of this study, published in PLoS ONE, focus on
an area of the brain known as the posteromedial cortex, which
has recently been implicated in personal memory.

"Our theory is that the posteromedial cortex may be our
brain's 'cruise control' that normally deactivates when we are
trying to remember things, so resources can be sent to other
areas of the brain that encode memories. However, in people
with mild cognitive impairment or Alzheimer's disease, the
deactivation does not happen and the posteromedial cortex
remains active," said Dr. Petrella.

The process of brain deactivation is similar to some other
common bodily functions. For example, when a person is
participating in a marathon, the gastrointestinal system
temporarily turns off so blood can be redirected to areas which
need it more, namely the muscles that are keeping the runner in
motion.

In this study, researchers conducted fMRI scans on 75
people, including 34 with mild cognitive impairment, 13 with
Alzheimer's disease and 28 with normal cognition. Study
participants completed standard neuropsychological testing and
were monitored with fMRI while performing a memory task
matching names and faces. Patients were then followed for three
and a half years to determine how their cognition changed over
time.

"At present we treat all people with mild memory loss the
same, even though some MCI subjects may convert in a year and
others may take five years," said study co-author P. Murali
Doraiswamy, M.D., chief of the division of biological
psychiatry at Duke. "This is because there is no single test
that can definitively predict who will develop late-onset
Alzheimer's or not. The ability to probe brain circuits at a
deeper level may help us diagnose risk with greater
certainty."

The researchers found that approximately a third of the MCI
subjects converted to Alzheimer's in three and half years after
their initial scans. The conversion to Alzheimer's was
determined by study doctors using routine clinical and memory
tests. fMRI level of deactivation was found to significantly
predict which MCI subjects converted to Alzheimer's.

While other studies have focused on the brain's ability to
turn on certain regions, this research determined that losing
the ability to turn off a region of the brain may be a more
sensitive marker of future cognitive decline

"The Holy Grail in this field is to predict with 100 percent
accuracy whether a 50-year old who forgets names will get
dementia or not. We are not there yet but are inching closer
and closer everyday. The combination of genetic, biochemical
and imaging biomarkers will soon become the gold standard,"
said Doraiswamy.

Dr. Petrella added, "Although we tend of think of
Alzheimer's as a disease causing shrinkage of discrete memory
centers, at its earliest stages it really disrupts neural
circuits. The diagnostic tests of the future will examine not
just structure but also the interplay between the many nodes in
the brain's memory circuits."

The study was supported by the National Institute on
Aging.

The complete study manuscript is available on the PLoS ONE
website: http://www.plosone.org/doi/pone.0001104.