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If you're new to this blog and want some context for it, read this post from the day I announced my Alzheimer's disease and this post about the day I announced I had lost it. For more info, visit my website with my autobiography and all blog entries in chronological order for easier reading to catch up. There's also a sermon on the spiritual lessons I've learned through this journey through my damaged mind.

Sunday, February 17, 2013

Research (2)

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.


  1. Didn't the last post report you don't have Alzheimer's? Now you're sure you have it? I'm missing something?

    1. Feb 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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