Cognitive Impairment: Improved PET Scans Show Plaques and Tangles

Cognitive Impairment: Improved PET Scans Show Plaques and Tangles

Positron emission tomography
(PET) of the brain using an enhanced
chemical marker has the
ability to differentiate among normal
aging, mild cognitive impairment, and
Alzheimer disease (AD). Researchers
writing in the New England Journal of
Medicine said the technique is "potentially
useful as a noninvasive method to
determine regional cerebral patterns of
plaques and tangles associated with
Alzheimer's disease."1

Eighty-three volunteers with selfreported
memory problems participated
in the study. On the basis of cognitive
testing, they were divided according to
their degree of cognitive impairment.
Twenty-five volunteers were classified
as having AD and 28 as having mild
cognitive impairment, while the remaining
30 were healthy controls with
no impairment.

Previous studies have found that α-
amyloid (in senile plaques) and tau (in
neurofibrillary tangles) "accumulate abnormally
in a predictable spatial pattern
during aging and Alzheimer's disease,"
the researchers wrote. The investigators
used a tracing agent known as FDDNP,
a molecule they developed that binds to
the amyloid senile plaques and tau neurofibrillary
tangles. They compared the
results to outcomes with a different tracer
known as FDG and to MRI studies of
the same patient group.

"Global values for FDDNP-PET
binding . . . were [significantly] lower in
the control group than in the group with
mild cognitive impairment . . . and the
values for binding in the group with
mild cognitive impairment were [significantly]
lower than in the group with
Alzheimer's disease," they wrote.
"FDDNP-PET binding differentiated
among the diagnostic groups better than
did metabolism on FDG-PET or volume
on MRI."

In comparing the 3 diagnostic methods,
the researchers wrote: "We found
that the values of global FDDNP were
more accurate than previously established
sensitive measures for FDG-PET
or volumetric MRI measures for diagnostic
classification of subjects, suggesting
that FDDNP may be useful in
differentiating among Alzheimer's disease,
mild cognitive impairment, and
normal aging."

One of the 83 subjects died 14
months after the baseline studies were
completed. A neuropathological examination
following an autopsy "showed
that regions of the brain with high values
of FDDNP binding are characterized
by high concentrations of plaques
and tangles. These findings support the
potential usefulness of FDDNP-PET in
the development of surrogate markers
for drug discovery aimed at blocking
amyloid buildup and as a diagnostic
tool, although the study does not provide
definitive evidence of a basis for
such uses."

The researchers concluded that,
"FDDNP-PET scans differentiate persons
with mild cognitive impairment
from those with Alzheimer's disease
and those without cognitive impairment.
Equally important, in vivo distributions
of FDDNP in the brain follow
patterns of pathological distribution
seen at autopsy. . . . These observations
suggest that FDDNP-PET may be useful
in the development of surrogate
markers for monitoring the accumulation of these abnormal protein aggregates
in the brain that are characteristic
of Alzheimer's disease."


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