What's Going On?

Washington DC

Now I’m confused!  In the past few months, I’ve been part of two separate research studies in which Positron Emission Tomography (PET) scans to look for amyloid plaques (one of the presumed causes of Alzheimer's) were normal, even though the two scans used different methods of measuring the amyloid. 

I also had a PET-glucose scan which ought to document damaged areas in the brain where the cells are not fully functioning.  That, too, was normal.  In other words, I’ve had three different brain scans, none of which indicated that I had Alzheimer's.  I’ve just reviewed the results with my doctor.

What is going on?

One possibility is that I needn’t take the results too seriously.  Medical tests are never perfect, and these particular tests have only recently been used to diagnose Alzheimer's.  We still don’t know enough about their accuracy to know anything with certainty.  But three different tests, using different methods and looking for different mechanisms, are unlikely to be wrong simultaneously.  My very rough statistical calculations is that, if I have Alzheimer's, the likelihood that at least one of scans would show something is in the neighborhood of 99.75%

A second possibility is that my symptoms are due to something else.  Although Alzheimer's is by far the most usual cause of dementia, there are two other fairly common causes, temporal-frontal dementia (TFD), where the damaged cells are in a specific area of the brain, and Lewy Body dementia (LBD where a protein different from amyloid gums up brain functioning.  But I would think that the PET-glucose scan should show problems in each of these diseases, too.  Vascular dementia (a series of small strokes) is also fairly common, but the scans, including the CT and MRI, should have ruled that out.  Further, according to the doctors, the specific combination of my symptoms doesn’t fit any of the three dementias.  And—given the other examinations, blood tests, and CT scans that I’ve had—there are no other reasonable possibilities causing dementia.

My doctor said that he still believes I have Alzheimer's.  But he’s certainly puzzled by the negative results.  The other possibility, he said, was that I was so early in the disease that both scans were negative.  If that’s the case, of course, it’s very good news.  But it seems to me highly unlikely.  I’ve had symptoms for perhaps five years and serious symptoms for three years.  In addition, plaque deposition in Alzheimer's begins at least fifteen years before symptoms appear.  Being too early in the disease doesn’t seem to me a reasonable explanation for all the normal tests.

Another (unspoken) possibility is that my symptoms are due to normal aging and that I’m among the “worried well,” a polite way of saying that my more severe symptoms are imaginary.  I have a difficult time believing this (although, of course, no one who’s just imagining symptoms is going believe it).  The neurologist hasn’t mentioned this possibility, but it has to be on his mind.  If it’s all in my imagination, then I’m not sure I’m relieved.  I’ve blanked out an entire day, lost my ability to do more complex calculations on a spreadsheet, gotten lost three times, have had to give up my usual writing and teaching, and had other major episodes.

As a part of the NIH study, I’ve been scheduled for a full (4 – 6 hour) neuropsychological exam at the end of the month.  When I asked the doctor at NIH to give me the results of the scans before the neuropsych exam, he hesitated.  Doctors don’t like to give patients partial results because people can worry or jump to weird conclusions.  I reassured him that as a physician I understood the problem.  So he gave me the results of the scans, and here I am worrying and jumping to weird conclusions. 

I’ll wait for the results of the neuropsych tests.

The specifics of my situation feel unique, but many people with mild cognitive impairment (MCI) find themselves confused and anxious because of the uncertainty involved.  I’ve written about some of the issues with MCI in early Alzheimer's before.  As I read more deeply, however, it seems that medical thinking about MCI is changing.  I’ve assumed that if a mild cognitive impairment is progressing, then it’s really just an early phase on its inevitable way to one of the dementias.  And this is certainly true much of the time.  But some doctors believe that MCI may be more complicated.  In some cases, they believe, it may be a specific diagnosis with its own cause that may stay stable or even improve over time.  But details are sketchy.

People now come to medical attention much earlier in the disease process.  Unfortunately, the appropriate tests, diagnostic criteria and medical understanding have not kept up.  When a person is diagnosed early in the disease, uncertainty is inevitable.  This isn’t a question of ignorance or incompetence: It’s just the nature of the disease.

No wonder I’m confused.