NEJM has a very interesting article about the use of PET
scans to differentiate between persons with normal cognitive function,
those with mild cognitive dysfunction, and those with Alzheimer
Disease (AD). Unfortunately, you need a subscription to view
full article, but you can read the abstract for free, so I’ve taken the
liberty of copying it here, then providing some plain-language
commentary. You also can read a more extensive review on Medscape
(free registration required).
of Brain Amyloid and Tau in Mild Cognitive Impairment
Volume 355:2652-2663; December 21, 2006; Number 25
Background Amyloid senile plaques
and tau neurofibrillary tangles are neuropathological hallmarks of
Alzheimer’s disease that accumulate in the cortical regions of the
brain in persons with mild cognitive impairment who are at risk for
Alzheimer’s disease. Noninvasive methods to detect these abnormal
proteins are potentially useful in developing surrogate markers for
drug discovery and diagnostics.
Methods We enrolled 83 volunteers with
self-reported memory problems who had undergone neurologic and
psychiatric evaluation and positron-emission tomography (PET). On the
basis of cognitive testing, 25 volunteers were classified as having
Alzheimer’s disease, 28 as having mild cognitive impairment, and 30 as
having no cognitive impairment (healthy controls). PET was performed
after injection of
(FDDNP), a molecule that binds to plaques and tangles in vitro. All
subjects also underwent 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, and
72 underwent magnetic resonance imaging (MRI).
Results Global values for FDDNP-PET binding
(average of the values for the temporal, parietal, posterior cingulate,
and frontal regions) were lower in the control group than in the group
with mild cognitive impairment (P<0.001), and the values for
binding in the group with mild cognitive impairment were lower than in
the group with Alzheimer’s disease (P<0.001). FDDNP-PET binding
differentiated among the diagnostic groups better than did metabolism
on FDG-PET or volume on MRI.
Conclusions FDDNP-PET scanning can differentiate
persons with mild cognitive impairment from those with Alzheimer’s
disease and those with no cognitive impairment. This technique is
potentially useful as a noninvasive method to determine regional
cerebral patterns of amyloid plaques and tau neurofibrillary tangles.
Basically, what they’ve done, is to develop a marker that selectively
binds to the abnormal materials that are found in the brains of persons
with AD. This marker can be detected very accurately with a
special device: a PET scanner. The accuracy is important,
because it is not enough to merely detect the marker; you have to be
able to tell exactly how much of the marker sticks in various parts of
Even though there were only 83 subjects in the study, the results seem
promising. If it turns out to be as good as it looks, this
will help solve a number of problems.
One of the difficulties in doing research on any disease is the problem
of getting a pure sample of people who actually have the disease, and
not some other disease that happens to resemble the disease you are
studying. AD is only one of many kinds of dementia.
Previously, the only way you could be absolutely certain of
the diagnosis was to get a sample of the patient’s brain tissue, and
look at it with a microscope. Obviously, this is something
that generally is not done on persons who are still alive.
This kind of PET scan will help solve that problem.
Another problem in doing research on potential cures or treatments, is
that you need some way to accurately and precisely measure how much
benefit the treatment provides. The sooner you can see a
benefit, the more quickly the research can progress. If, say,
you are studying something that you hope will delay the onset of AD, it
could take ten years of observation to know if you are on the right
track. Anything that speeds that up will be welcome.
The conclusion: for now, I see this as being important primarily as a
research tool, not as something that will be done routinely in clinical