Alzheimer's, Dementia & Mental Health
It May Not Be Amount of Plaque in Brain but Where It
Builds That Can Predict Cognitive Decline
Relatively early accumulation of plaques in temporal
lobe was associated with cognitive decline
July 15, 2013 – The build-up of amyloid plaque –
clumps of abnormal proteins – in the brain has long been linked to
Alzheimer’s disease but researchers have not been able to explain why
many people with plaque accumulation do not develop dementia. New
research says the trajectory of this amyloid plaque buildup may serve as
a more powerful biomarker for early detection of cognitive decline
rather than using the volume of plaque.
Amyloid plaque that starts to accumulate relatively
early in the temporal lobe, compared to other areas, and in particular
to the frontal lobe, was associated with cognitively declining
participants, in the new study by researchers from
Department of Radiology. It is published today in
"Knowing that certain brain abnormality patterns
are associated with cognitive performance could have pivotal importance
for the early detection and management of Alzheimer's," said senior
Davatzikos, PhD, professor in the Department of Radiology,
the Center for Biomedical Image Computing and Analytics, at the
of Medicine at the University of Pennsylvania.
Memory decline and Alzheimer's - 5.4 million
Americans live with it today - is often assessed with a variety of tools,
including physical and bio fluid tests and neuroimaging of total amyloid
plaque in the brain.
Past studies have linked higher amounts of the
plaque in dementia-free people with greater risk for developing the
disorder. However, it's more recently been shown that nearly a third of
people with plaque on their brains never showed signs of cognitive
decline, raising questions about its specific role in the disease.
Now, Dr. Davatzikos and his Penn colleagues, in
collaboration with a team led by Susan M. Resnick, PhD, Chief,
Laboratory of Behavioral Neuroscience at the National Institute on Aging
(NIA), used Pittsburgh compound B (PiB) brain scans from the
Longitudinal Study of Aging's Imaging Study and discovered a
stronger association between memory decline and spatial patterns of
amyloid plaque progression than the total amyloid burden.
"It appears to be more about the spatial pattern of
this plaque progression, and not so much about the total amount found in
brains. We saw a difference in the spatial distribution of plaques among
cognitive declining and stable patients whose cognitive function had
been measured over a 12-year period. They had similar amounts of amyloid
plaque, just in different spots," Dr. Davatzikos said.
Editor’s Note: A spatial pattern
arranges things according to how they fit together in physical space;
i.e., where one thing exists in relation to another.
"This is important because it potentially answers
questions about the variability seen in clinical research among patients
presenting plaque. It accumulates in different spatial patterns for
different patients, and it's that pattern growth that may determine
whether your memory declines."
The team, including first author Rachel A. Yotter,
PhD, a postdoctoral researcher in the Section for Biomedical Image
Analysis, retrospectively analyzed the PET PiB scans of 64 patients from
the NIA's Baltimore Longitudinal Study of Aging whose average age was 76
For the study, researchers created a unique picture
of patients' brains by combining and analyzing PET images measuring the
density and volume of amyloid plaque and their spatial distribution
within the brain. The radiotracer PiB allowed investigators to see
amyloid temporal changes in deposition.
Those images were then compared to California
Verbal Learning Test (CLVT) scores, among other tests, from the
participants to determine the longitudinal cognitive decline. The group
was then broken up into two subgroups: the most stable and the most
declining individuals (26 participants).
Despite lack of significant difference in the total
amount of amyloid in the brain, the spatial patterns between the two
groups (stable and declining) were different, with the former showing
relatively early accumulation in the frontal lobes and the latter in the
A particular area of the brain may be affected
early or later depending on the amyloid trajectory, according to the
authors, which in turn would affect cognitive impairment. Areas affected
early with the plaque include the lateral temporal and parietal regions,
with sparing of the occipital lobe and motor cortices until later in
"This finding has broad implications for our
understanding of the relationship between cognitive decline and
resistance and amyloid plaque location, as well as the use of amyloid
imaging as a biomarker in research and the clinic," said Dr Davatzikos.
"The next step is to investigate more individuals with mild cognitive
impairment, and to further investigate the follow-up scans of these
individuals via the BLSA study, which might shed further light on its
relevance for early detection of Alzheimer's."
Co-authors of the study include Jimit Doshi, MS,
and Vanessa Clark, PhD, of Penn Medicine, Jitka Sojkova MD of Johns
Hopkins School of Medicine and NIA, Yun Zhou, PhD, and Dean F. Wong, MD,
of Johns Hopkins School of Medicine, Luigi Ferrucci, MD, PhD, and Susan
M. Resnick, PhD, of the NIA.
This research was supported in part by NIH grant
NIA-R01-14971, by the Intramural Research Program of the NIH, National
Institute on Aging and by NIA Research and Development Contract
Neurodegenerative Disease Research
of Medicine at the University of Pennsylvania
Pennsylvania Health System
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