The Corpus Callosum

Early Diagnosis of Alzheimer Disease?

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
the
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 href="http://www.medscape.com/viewarticle/549894">Medscape
(free registration required).

href="http://content.nejm.org/cgi/content/abstract/355/25/2652">PET
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
2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile
(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
the brain.  

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
practice.

Comments

  1. #1 stewart
    December 27, 2006

    What’s the cost of the test? What are the alternatives?
    I ask because, as a neuropsychologist, I see a number of reports of imaging studies that claim a 80-90% diagnosis rate. The predictive rate for targeted neuropsychological assessment (DAT or MCI?) is as high or higher than those studies (I haven’t gone through all the detail on this NEJM paper yet) at considerably less cost. That’s the tool that is likely to be most useful for clinical diagnositics. The other is interesting for research, but too expensive for general use.

  2. #2 Joseph j7uy5
    December 27, 2006

    I don’t know how much they cost. Since it is done in a research setting, there is no literal price tag.

    I think the main value of the PET scan is to be able to quantify the extent of the changes that are occurring on a cellular level. I can’t think of any other way to do that.

    General information about PET costs can be found here:
    http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat6.section.2250

  3. #3 Roy
    December 28, 2006

    GMTA, Joe. I’ve got a pic from the article over on Shrink Rap.

    PET scans generally go for about $US2000, though I’m sure the FDDNP will add to it. I agree that it won’t be a clinical tool for some time, but it can aid in early diagnosis, thus prompting additional drug studies looking for drugs with further delay the development of cognitive signs of degeneration. They could market this to pharmco’s to use as a research tool. Medicare and insurance companies will not be quick to approve this for general use (not at 2 grand a pop), but the drug companies might spring for it.

  4. #4 Organic Chemistry
    March 15, 2007

    It does look promising to a layman (with a chemistry degree)….I would ask the researchers if they had a problem getting the tag across the blood-brain-barrier and how it is removed from the brain.