Washington DC
Last week, Marja and I went to our first interview at
the Georgetown Hospital Clinical Research Center. I want to enter a study of an experimental
drug that is being tested to see if it actually alters the physical
degeneration of Alzheimer disease.
Virtually everything medical science knows about the
disease is uncertain, including the diagnosis, which can’t be made with
certainty until autopsy of the brain.
But (for the more medically inclined) it may help for me to explain the
most commonly accepted hypotheses about how Alzheimer’s develops and what this
particular research study is about.
A definitive diagnosis of Alzheimer’s can only be made
after death by autopsy evidence of neuron destruction and shrinkage of parts of
the brain. Microscopic examination of
the neurons and the spaces between neurons (synapses) reveals “neuro-fibrillary
tangles,” which are threads of intracellular proteins that have been snarled by
another protein called tau. These tangles
impair the communication between neurons that is essential for all brain
functions. There is also an “amyloid
plaque” that is involved—sort of a protein goop that builds up around the
synapses—that also interferes with communication among nerve cells. Presumably the neuro-fibrillary tangles and
the amyloid build up over many years causing progressive impairment of brain
function.
(For the non-medically inclined, the cause of
Alzheimer disease seems to be the destruction of neurons by two proteins [amyloid
and tau], both manufactured by the body itself.
Only an autopsy of the brain can definitively identify this kind of
brain destruction.)
In practice, however, the diagnosis is usually made first
by testing for impairment of memory and other cognitive abilities and then
excluding the possibility of other causes of dementia, such as strokes,
Parkinson’s disease, or vitamin B deficiency.
Such a diagnosis by exclusion, however, tends to seem vague and
uncertain to non-medical people, which can cause stress, not only for the
patient but also for friends and family.
Recently there have been new developments to help in
diagnosis. Positive Emission Tomography
(PET), a brain scan somewhat similar to an MRI, can show the build-up of
amyloid plaque in the brain. A spinal
tap (lumbar puncture) can show increased levels of the tau protein in the
spinal fluid. Neither test is definitive
but, when added to abnormal cognitive tests, each gives objective evidence to
buttress the diagnosis.
The drug being tested in this study has the potential to
actually change the underlying pathology of the disease. The only drug currently approved for treatment
of Alzheimer’s, Aricept (donepezil HCl), and the others waiting in the pipeline
for approval may lessen the symptoms of the disease, at least for a while, but
they don’t slow down the build-up of amyloid or neuro-fibrillary tangles, so
the brain continues to deteriorate even though symptoms may temporarily
improve. According to the Federal Drug
Administration, Aricept isn’t even terribly effective
at ameliorating symptoms; advertisements for its efficacy exaggerate what’s
been found in controlled studies.
Because my symptoms are not yet disruptive, I haven’t been taking
it. But both the study nurse and my
neurologist have recommended it, so I’ll begin now before the research study
gets underway.
The research I’m trying to sign up for, however, will
study whether an experimental drug (that doesn’t even have a name yet) could
halt or even reverse the build-up of amyloid in the brain. The research is very early; it’s only in
“Phase 2,” which it’s primarily being studied for safety and tolerance; a later
Phase 3 would test for effectiveness. It
would be an exciting breakthrough.
For me, what was most interesting about going in for the
study was all the information and attention we received. The study protocol require Marja to accompany
me throughout, so we biked over to Georgetown, and a nurse spent over an hour
with us, exhaustively explaining the study, answering our questions, taking
blood samples, and repeating a cognitive test.
During our interview Marja had mentioned that she, too, was concerned
about cognitive impairment, so she took the same test. But both of us received perfect scores,
which, the nurse said, was not unusual early in the disease with this basic screening
test. I found it all fascinating.
But the best thing about the research is that I will
be studied quite intensively and followed for two years. It means that I will get not only the PET
scan (very expensive and not covered by Medicare) but also the spinal tap. So, assuming those tests are positive, I’ll have
as definite a diagnosis of Alzheimer’s as is possible before autopsy.
That’s important to me because so far, honesty has
compelled me to inform people that I have mild, progressive cognitive
impairment and that the diagnosis of Alzheimer disease is not certain. That’s technically true, but—since neither my
neurologist, the nurse at Georgetown nor I doubt it’s Alzheimer’s—the tests will
allow me to feel more comfortable telling people I have Alzheimer disease and avoid
the equivocation that so often leads to annoying conversations about whether I
really have the disease. I get sick of
it.
I suppose in some small corner of my mind, I have some
doubts, too. I’m mostly participating in
this study because I believe that, ultimately, medical studies are the only way
to discover an effective treatment for Alzheimer’s. But I’m also happy I’ll be getting this PET
scan and the spinal tap (three times each no less), which will finally nail the
diagnosis down.
Didn't the last post report you don't have Alzheimer's? Now you're sure you have it? I'm missing something?
ReplyDeleteFeb 9, 2014 - Robert: For whatever reason this comment got posted from a blog entry a year ago. But if you're confused about whether I have it/don't have it, you're not alone. It's been a wild ride. You'll find the latest post Jan 29, 2014 "Letting go for the Third Time"
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