Tuesday, December 07, 2004

It’s Still Ticking (Part I)

Why the hell didn’t anyone bother to read the fine print?
Y’know, it’s one thing to make an honest mistake and feel silly about it. However that feeling is something altogether different when it follows an egregious, boneheaded error — especially when in so doing, its consequences place your own wellbeing or that of your family in danger. That feeling is a little bit harder to take.

Now I’m probably not too far off base in assuming that most of us don’t spend a goodly amount of time with our noses buried in scientific/medical journals (with the Burner notably excepted). To say that they’re a tedious read for the layperson would be an understatement. But I’m still trying to figure out how we all could have so completely missed what I have now discovered to be a somewhat obvious caveat to the assumption that we were all ‘out of the woods.’ It’s as puzzling as it is exasperating. The only thing I find more amazing than the error I made in assessing the final published AD study results is that we all apparently made the same glaring oversight.

I am now convinced that no one in my family really read the report when the test results were first published in 1992. Perhaps we only saw what we wanted to see. And though we eventually would assume that the report cleared our immediate family from danger, there was indeed reason for concern initially — about me in particular.

Forest?…What forest?
I guess I need to clarify something. I have to this point indited my entire immediate family for misunderstanding the test results, but I really need only to personalize it, because I really can’t say for sure what anyone else’s thoughts and understandings were. I can only go by the reaction everyone had to the nightmarish realization that Alex was showing signs of AD. No one except my older brother TK thought that it was possible, and that opinion was only one of hindsight. He recently related to me that he noticed Alex’s behavior beginning to change, in his opinion, as early as 2000, the year Alex turned 40. Alex was doing some legal work for an entrepreneurial project TK was engaged in and he reportedly displayed a measure of confusion and outright lack of competence that was totally unlike him. TK said he was surprised, but that he never put two-and-two together until recently.

Whether or not Alex has actually been affected by AD for that long is debatable; his wife insists she didn’t see any signs until just over a year ago (around August of 2003). However anytime within the past four years would be consistent with the onset pattern displayed by most of the affected members in my family. The point is, no one saw it coming — not even remotely. It was the quintessential example of ‘not seeing the forest for the trees.’

In fact, back in 1992 when the report was first published, there was much more of a concern that it would be me, not Alex at whom fate would point its bony finger.

The study, published in the international medical journal, The Lancet, gave a fairly detailed and concise breakdown of the control subjects whose DNA were used in the test. It detailed the correlation between each participant’s level of Amyloid Precursor Protein (APP) found in the cerebrospinal fluid (CSF) that each of us had given via spinal tap when we all converged on Indiana University Medical Center in April 1992, under the auspices of Dr. Martin Farlow.

The study involved four generations of my family. Its range includes my Grandfather (Generation I), who was the carrier of the AD gene from yet other previous generations of his family line in Rumania, to my brother David’s three children (Generation IV), who now must also deal with the specter of possibly developing AD later in their lives. And now Alex’s three children must also be added to that dubious roster.

Born of my Mother and her two other AD-affected siblings (Generation II) were the ten members of “Generation III,” comprised of my four brothers, five cousins, and me. We Gen3’ers were the focal point the study, as we, with the exception of David, were yet unaffected and represented a wide cross-section of age, ranging from pre-to-near typical onset age (31-45 years old). We each participated in the same battery of neuropsychological tests, blood sampling and the most fun of all, spinal taps for gathering cerebrospinal fluid (CSF). As uncomfortable as they were, the spinal taps were the key to the test.

From the Science Magazine article, the above chart is the “pedigree” of AD in my family. Note that the filled-in (black) symbols indicate gene-carriers. “Generation III” (the third level of the pedigree) is the group featuring my immediate family and cousins to whom the genetic testing was directed.

There were actually two major research write-ups on Dr. Farlow’s work, spaced about a year apart. The first one, in October 1991, detailed the discovery of the genetic mutation on Chromosome 21 and was published in Science magazine in August of that year. That article made the initial observation that unusually low levels of APP appeared to be a common link among those who carried the point mutation associated with Early Onset AD.

In late 1991, a researcher in California, Dr. Stephen Wagner of Salk Institute of Biotechnology in La Jolla, CA (that’s pronounced La-HOY-AH for all you non habla espanol or non Left-Coasters) read the Science article and contacted Dr. Farlow immediately. Coincidentally, he had independently been working on a way to measure levels of APP in spinal fluid. It was this convergence of research between Drs., Farlow’s and Wagner that made the test possible, paving the way for the Lancet article in August of 1992.

There were additional newspaper articles, even an episode of PBS’s Nova that proclaimed the importance of the research’s inroads. And while all of the scientific acclaim was a nice thing to be a part of, there was no one in my family who really understood it, no matter how much we wanted to pretend we did — certainly not me, anyway, and most likely, not Alex either. All we really knew before the report was published was that Dr. Farlow had discovered the genetic mutation, which causes the family time bomb to tick. All we really wanted to know after report was published was, for whom?

Is it “C” or is it me?
You may have noticed that twice I have made reference to the notion that we all surmised that with the obvious exception of David, the rest of out immediate family was ‘out of the woods.’ However initially there was some concern that I was not.

The reason I’ve yet to explain why is because it has to do with detailing the actual findings of the Lancet report, and I didn’t want to be all over the map with my references to it. This story is hard enough to tell even without all the technical details, and I’m bound and determined to make it understandable to everyone if at all possible. So I’m trying to keep the details in a steady, logical progression.

From this point forward, however, it may be difficult to follow the game without a scorecard, but I’ll try to keep the tedium to a minimum.

Ironically, it was Alex, the family’s self-appointed secretary of State, and being an attorney, most logically, the executor of my Father’s will, who distributed copies of the Lancet report to each family member via mail in late August, 1992. He was the one who kept in contact with Dr. Farlow and advised us of new developments following our group research encounter that previous April.

When I first read the two-page article, I remember the tingling sensation in my gut. What was I looking at, really? Would I be able to divine my future from this morass of fifteen-dollar words? From the outset, the actual number of participants in the study was just sort of a foggy detail that I don’t ever remember really addressing, let alone establishing in my mind. The first time I read it, only one thing jumped out at me. It would continue to tattoo a deadening pulse of dread in the back of my neck for the next nine months.

There on the first page, the report detailed the disposition of the test subjects who had been determined to carry the genetic mutation. “One of the two symptom-free gene-carriers (M1; aged 35 years) had good intellectual abilities with no deficits in memory or cognition…

It just so happened, that’s how old I was at the time. But it was also the age of one of my cousins (who we’ll call “Cheryl”), who along with her older sister (who we’ll call “Denise”) was also a part of the study. So, in a circumstance in which I knew that I already had a 50/50 chance of acquiring the disease, I was now faced with another 50/50 proposition. Was the report indicating that it was my cousin or me who tested positive for the AD gene?

I can’t say for sure how much, but I’m sure it was the distraction of the cloud’s return to its previous overhead position of uncertainty in my life that threw me off initially. The details of how many family members were involved in the test results (a fact that doubtless played the biggest role of all in our self-deception) was something that I don’t ever remember directly reading or questioning. I just assumed that it was all ten of us. The actual number was the least of my worries. I was scared shitless. Here I was, 4-7 years away from the typical age of onset, having just moved my family halfway across country, living in a small apartment, self-employed with two young children and no health insurance. I could no more afford private disability insurance than the man in the moon; yet I needed to do something to plan for the future of my family. I was paralyzed and despondent. I wanted to go off, find a nice big rock and crawl under it.

But it is now obvious that we were my own worst enemies. I’m now certain that we in our own minds blurred the distinction between research and diagnosis. Not to say that the research was flawed in any way, but from the outset, we were repeatedly discouraged from reading too much into the test results or trying to guess ‘who was who.’ Again we were told by Dr. Farlow that if we really wanted to know, we would have to go through the established channels to learn what our individual results were.

We were reminded of IU’s legal policies, requiring the signing of a number of legal liability release forms before he could give out any definitive information. And of course, the signing of the release forms was only the tip of the iceberg, that in the grand scheme of potential knowledge, if you don’t have insurance already in place and test positive, you would be uninsurable from that point forward. It was a vicious cycle. I didn’t have the insurance and didn’t know when I would have. I was helpless to do anything but hope, pray, and twist in the wind.

But somehow we worked through it. Michelle was incredibly supportive. This was something she knew she was possibly signing up for when she married me. We clung to each other and to God for strength. I did my best to establish my business in my new home, and things began to develop well. I had steady work, Michelle found a good part-time job, and we began to seriously consider looking for a house to buy. The cloud was again barely noticeable, but it still never disappeared completely. There was always the pressure to ‘get my act together’ financially, so that I could in good faith learn once and for all whether or not I had the family’s genetic predisposition for Alzheimer’s.

But then in April I would receive a phone call that would change my plans — not to mention the weather.

Next: Loose Lips…
blog comments powered by Disqus