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Alzheimer's & Dementia
Autopsies Show Mild Cognitive Impairment Leading to
Alzheimer's
Brains
had plaques and tangles beyond what's expected in normal aging
May 8, 2006 – Autopsies of persons who had only
mild cognitive impairment revealed structural changes in the brain that
indicate these people with slight behavioral symptoms were on their way
to developing Alzheimer's disease. Mild cognitive impairment has been
considered a strong early predictor of AD but this is one of the first
autopsy studies of such patients.
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“I think our study provides an anatomical basis for
the clinical condition of mild cognitive impairment,” says Joseph Parisi,
M.D., Mayo Clinic neuropathologist and study investigator. “This shows
that there are structural changes in the brains of patients who may
develop Alzheimer’s disease.”
This study, led by Mayo Clinic and funded by the
National Institute on Aging, is one of the first autopsy studies of mild
cognitive impairment. Findings will be published in the May issue of
Archives of Neurology .
“Our examination of the brains of those who died
while they had mild cognitive impairment shows us that
neuropathologically they are not normal, but they do not have the
changes of fully developed Alzheimer’s disease,” says Ronald Petersen,
M.D., Ph.D., Mayo Clinic neurologist and study investigator.
“These early findings led us to believe that these
people were on the road to developing Alzheimer’s, but they weren’t
there yet. They have only a few of the features of Alzheimer’s in their
brains. Just like they clinically looked in between normal aging and
Alzheimer’s disease, their brains also looked in between. It is a
confirmation of a transitional condition between normal and Alzheimer’s
disease.”
The study’s intent was to determine the features of
the brains of those who died while in the clinical state of mild
cognitive impairment, showing behavioral symptoms of the condition.
Autopsies were performed by Mayo Clinic pathologists on the brains of 15
people who died while they had clinical mild cognitive impairment, as
well as on the brains of 28 patients who were cognitively normal and 23
with probable Alzheimer’s, a disease that ultimately can only be
diagnosed after death.
The researchers found that most of the brains of
those who had been clinically diagnosed with mild cognitive impairment
did not meet the pathological criteria for Alzheimer’s disease, but
rather showed changes suggesting progression toward Alzheimer’s.
All these brains possessed plaques and tangles —
hallmarks of Alzheimer’s disease — beyond what would be expected in
normal aging, yet shy of full Alzheimer’s. Plaques and tangles result
from deposits of abnormal proteins in the brain, causing a slowly
progressive loss of neurons.
“Mild cognitive impairment is by definition a
disorder of cognitive function,” says Dennis Dickson, M.D., Mayo Clinic
neuropathologist and study investigator. “When we look at the brain, we
can’t see cognition, but we can see degenerative changes.
"In general, in the brains of those with mild
cognitive impairment the plaques and tangles that are the hallmark of
Alzheimer’s disease were present, but in less severity and confined to a
specific area, unlike Alzheimer’s, in which plaques and tangles are
widespread throughout the brain.”
Dr. Dickson points out that density and spread of
plaques and tangles are not sufficient alone to identify those who are
normal or who have mild cognitive impairment or Alzheimer’s.
“Some people can compensate for the pathology in
their brains,” he explains. “They can have a high burden of plaques and
tangles and yet be normal. This may be due to factors like education,
activity or life experiences.
"If I sat down and grouped brains by normal, mild
cognitive impairment and Alzheimer’s, I’d be wrong in a number of cases.
It doesn’t map exactly that if you’re normal you have no plaques and
tangles, and if you have Alzheimer’s you have a large amount of plaques
and tangles. But generally, the more plaques and tangles you have in the
brain, the more cognitively impaired you will be.”
The plaques and tangles that are present in the
majority of the brains of those with mild cognitive impairment will lead
to a gradual breakdown of the very elaborate circuitry of the brain in
which normal neurons stop functioning and memory is affected, says Dr.
Parisi.
“Everything’s wired in the brain,” says Dr.
Dickson. “When a neuron dies, it’s as if that circuit is shorted out,
which presents itself as cognitive impairment and eventually dementia.”
The researchers say that people can contribute to
research in Alzheimer’s and its preconditions by having an autopsy
performed on a loved one with such a condition.
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