Monday, December 13, 2004

It’s Still Ticking (Part III)

Just when I thought that I was out…they pull me back in!
Not that I consider myself a movie aficionado like a lot of people, but I definitely enjoy ‘em. And there are a few movies — and movie quotes — that I dwell upon and allow to spin around in my mind from time to time. While the persona might be a bit of a stretch, one character whose life I can’t help but identify with to some degree is The Godfather’s Michael Corleone.

No, I’m not a gangstah…work with me, people.

If you’re familiar with Godfather trilogy, you know that it revolves around a primary character whose essence is a mixture of a man who is a victim of his circumstances and a one who sells his soul to power. In the beginning he is innocent and idealistic; unwilling to become a party to “the family business.” However as the story builds he is overcome by a destiny that he did not choose and becomes the very thing he despised.

Then later in his later years, when he is able to finally reevaluate his life, he decides to walk away from his past and embrace a new, positive future. Yet his destiny again steps in and reminds him of who he really is.
“Just when I thought that I was out…they pull me back in!”
— Michael Corleone, The GodFather, Part III

I feel like that sometimes with regards to the family curse. I’m sure that my brother Alex does right now. Not to say that we ever did anything to deserve what has befallen our family. With all due respect to my brother TK, I don’t think that this is an issue of karma. Sometimes things just are what they are. We will never know why, so there’s no reason to be angry or bitter. Things “is what they is.” In that regard, I know that Alex is at peace. However there continues to be one thing that haunts me, not only for the obviousness of it, but most importantly, for its potential consequences toward Alex.

So who goofed? Dr. Farlow? Nope. The Lancet Report? Negatory. My 3rd grade Elementary School teacher? Maybe. Me? Most definitely.

Me? You’ve gotta be joking! What could I have done that would have any effect on whether or not Alex has Alzheimer’s disease?

It was nothing anyone in the family or I did, but rather what we didn’t do.


That’s all we would have had to do in order to know, all the way back in 1993, that at least three more of my family members could potentially be carriers of the genetic mutation that leads to Early Onset Alzheimer’s disease (EOAD) in my family. It was right there in black and white in the Lancet report; not lying hidden amongst sentences of fifteen-dollar words, but plainly visible — not just once, but twice. There were just so many trees…I just couldn’t see that there was a forest there staring me in the face.

What was it? See if you can figure it out from the highlighted Lancet excerpt below.

Did you see it? It’s one word. One word that I never cognitively added into the equation from the first read in August 1992, until just a few weeks ago as I began to prepare for this story.

Six — as in “CSF was collected from six members of the family (aged 31-45 years) by sterile lumbar puncture.” Why is the number six so important? Because there were TEN of us, that’s why! Six out of ten genetic samples were used in the study, when all the while we thought that ALL of us were included, thereby leaving no one to chance. The upshot, of course, is while we thought that we were all accounted for in the study, we were in fact not. And that left the possibility that one or more of us still retained the possibility of bearing the AD gene in addition to the three that were included and so indicated in the Lancet report testing.

There are a few points of minutiae (sorry Todd…) that I need to mete out at this point which I hope will not serve to muddy the waters any further, but need to be noted, so please stay with me.
  • I’m just lookin at some tush…(Say WHAT, Doc?)
    While there were ten members of Generation III who were involved in the testing, only nine were actually eligible for inclusion in the final test study. One was removed for consideration at the last minute. This is something that we did not learn until a couple years afterward. It is just another clue that went unnoticed, but one that was clearly visible in the Lancet report. However the clue itself is also one of the primary elements that masked the truth from me. Whether the same could be said for the others in my family who believed the same as I did, I cannot say.

    It involves my cousin Kay, who at age 48 was by three years the eldest of the ten Gen3 family members in 1992. Yet the Lancet report says that the age range of the family members was 31-45. My Eldest brother Jack was 45 years old at the time of the testing, so clearly he was the end of that spectrum. Why wasn’t Kay included in the group? It’s actually a rather funny story.

    When Dr. Farlow called us all up to Indianapolis for the testing in April, 1992, it was somewhat of a staggered rotation. For example, all of my immediate family was there at the same time, but none of my cousins were. The two other extended family groups either preceded or came in after us. That’s why I still haven’t seen my cousin Cheryl since the 60s. She and Denise tested at a different time than my brothers and me. Likewise, the children of my Uncle Matt, of whom Kay was the eldest of his three children.

    According to the story I would hear two years later, from her younger sister, Janice, she and Kay were in the unenviable position of having their CSF and blood samples taken. The cerebrospinal fluid was drawn via a spinal tap, which if you’ve never had one done, is one of the more unpleasant experiences in life in my opinion. They ask you to remove your clothes and don a hospital gown — you know, the ones that open all the way up the back? You then lie down completely motionless on an exam table while they stick a syringe needle into your spine down around the tailbone to draw out the spinal fluid. It’s a painful and nauseating experience to be sure.

    But as Kay was lying on the table, her backside exposed from head to toe, the attendant who was conducting the CSF extraction, assumedly to lighten the mood and place her at ease, made a quite unfortunate — and uncalled for statement.

    “Has anyone ever told you that you have a nice tush?” He said. Receiving it in the spirit it was received, Kay deadpanned, “Sure, my husband tells me that all the time” or something to that effect. I’m sure the two of them laughed and thought that was the end of it, but no. Kay mentioned the comment to her husband, and all hell broke loose. He was furious. He forbade Dr, Farlow from using Kay in the study and spirited her off, back home to California. Of course no one knew until later that Kay had been removed from the study, but the fact that this incident occurred played a large role in obscuring the focus that we should have had — that I should have had — when we examined the data.

    As fate would have it, it turned out that in fact Kay did carry the gene. She began showing signs in the mid–to-late 90s and passed away just five weeks after Maxine, in July of 2000, at the relatively advanced age (for our family’s onset-to-death history) of 56. I believe that had she been included in the IU study and shown to test positive in the report, perhaps we would have paid a little more attention; perhaps we would have looked a bit more closely into what the Lancet report was actually saying. I don’t know for sure what the difference it would have made, but I can’t help but believe that her exclusion was just one more invisible distraction to our seeing the truth.

  • Semantics?
    The following may be the most convoluted of all, but in my understanding of myself I find it to be the most likely of all explanations for my gloss-over of the study participants number. I know how my mind works. I’ll be the first to admit that I have no qualms about asking for directions when I’m lost. If the teacher explained something in school that everyone else seemed to understand, but I didn’t, my butt was up at her desk as soon as class was over, asking questions. So when the Lancet report came out, written in a manner pointedly intended for those of the scholarly persuasion to understand, I was more than happy when cousin Samantha sent me the Associated Press article, which capsulized the study in terms a non-geneticist could digest.

    Who needs the scientific mumbo-jumbo when you have the explanation in plain English? Consequently, I may have skimmed through the Lancet report a few times, but I don't recall ever really reading it until just a few months ago — and I still didn't get it until just recently.

    The AP article pretty much explained the whole thing, I thought, in a clear and concise way. And I still think that, with one notable exception. But after now having the advantage of time and analysis, and most importantly the reality of knowing that Alex has AD, that one notable exception is significant. I believe that there was a misunderstanding on the part of either the article’s author or his editor in a key paragraph of the story. It’s extremely subtle, but sufficient to further obscure the otherwise obvious concept of there being of six — not ten family participants in the study.

    Again, below is the detail excerpt from the Lancet report:

    Look again at the first highlighted sentence. “CSF was collected from six members of the family (aged 31-45 years) by sterile lumbar puncture.” Now does the location of the parentheses indicate that the six selected members are aged 31-45 years, or is it saying that the entire family group was aged 31-45 years? Semantics, yes, but it is an extremely important point. You see, 31-45 was the exact span of ages for my family alone. The remaining four cousins just happened to fall within that same span, except for Kay, whom we didn’t know wasn’t included until well after the report came out.

    Never bothering to reconcile the fact that the math didn’t work, I always assumed that because all of our ages were included, all of my brothers and I were a part of the final test group — just because of the casual wording of that sentence.

    It appears the author and/or editor of the AP article must have thought the age range was referring to the final test group as well. The article's paraphrase of the age-range statement further inferred that understanding by eliminating the parenthesis altogether.

    And since I spent little time trying to decipher the difficult-to-read Lancet report in favor of the more layman-friendly AP version, this idea became cemented into my understanding of our entire circumstance.

    I don’t believe there to have been any irresponsibility on the part of either Dr. Farlow’s group or the writer of the AP article. The irresponsibility falls squarely upon my family and myself, who wanted to fudge a diagnosis out of that which was never ever intended to be a diagnostic vehicle. The IU study and published reports were intended only for their research value. If Dr. Farlow’s group is at fault at all it’s that they made it too easy to connect the dots. I learned in discussing this with some of the IU personnel on my recent trip there with Alex that it is not uncommon for researchers to deliberately switch around potentially identifying data such as age or sex for the purpose of obscuring identities in the publishing of a research white paper.

    The fact of the matter is that we should have all gone through the appropriate channels to learn of our own genetic disposition with regard to Alzheimer’s. And just because it wasn’t possible in the beginning, we should have followed through at such a time when our financial standing made it so. We shouldn’t have assumed that we weren’t at risk, regardless of the inference of a research paper which itself left wide open the fact that three of the possible nine in the test pool weren’t even included in the final results, if we’d bothered to open our eyes and see it.

    Like I’ve said before, I’m not a doctor or a scientist — and it’s probably a good thing. Based on my exhibition of thoroughness in thinking all of this through, I probably wouldn’t be a very good one. I suppose everyone else fell into the same trap. Not once did any of my family offer up a “but what if” scenario. We were all secure in the alleged knowledge that we had fought the dragon and all except our beloved David dodged the beast's fiery breath. They say “ignorance is bliss.” Well we were a pretty blissful bunch. It was a sober bliss, but bliss nonetheless.

    But what does it matter, really? After all it was inevitable. Why then such regret? Only that if Alex had known that there was a possibility of his developing EOAD, he might have been able to avail himself of treatment sooner. Our cousins Denise and Cheryl were pioneers in the testing of Alzheimer’s drugs, and the results were and still are significant in delaying the debilitating dementia that rapidly overtakes AD sufferers within a few years of onset. If treated early, Alex could have retained much more of what he has already lost for who knows how much longer. No AD drug will be effective forever, but the strides that have been made in the past few years are highly significant. And that is the basis of my regret and sorrow for my little brother; that he could have taken advantage of that and perhaps, kept more of himself, for longer.
A final note on the Lancet Report
I first posted hyperlinks to the Lancet and Associated Press articles in the previous blog entry of this series and some of you actually dove in and offered some legitimate questions as to what “the mistake” actually was. I hope you understand that there was no mistake with the APP-related test, which was the subject of this study. The test was not the method by which the final determination of genetic disposition was made, but rather an attempt to find an easily detectable “smoking gun” that would raise the red flag of indication that the subject indeed is a carrier of the genetic point mutation. Some of you have related to me the fact that parts of the study seem to admit to the test as being not entirely conclusive in its own assertion that the APP levels always indicate the presence of the mutation. And while that is true, it still does not invalidate the test as valid research. As I indicated previously, this research has successfully spring-boarded further research efforts in related areas, so it has indeed been both successful and fruitful.

So please believe me when I say that I harbor no ill will toward anyone at IU Medical Center. I no longer ask “how could they have allowed this to happen?” It was not their responsibility to tell Alex that he had the gene. When I asked Dr. Farlow in October to explain why we could have been so wrong to assume we all were in the clear when the ’92 research indicated just that, he seemed dumbfounded. “I’m sorry AJ, but I don’t know what you’re talking about.” I went on to explain how we had kind of used the research to connect the dots regarding our own disposition and he told me that research is research, and is never intended for use as diagnosis. He went on to say that when a person submits himself or herself for diagnosis of the AD gene, they triple-test to make absolutely sure.

We on the other hand, opted for the shortcut.

Therefore while I am saddened irrevocably for Alex, I’m also sobered by the reality that I too may be one of the three whose DNA was not part of the final test group, meaning that I might also carry the AD gene myself. I’m somewhat buoyed by the fact that at age 48 I have yet to experience any difficulties with my memory (well no moreso than I have all the rest of my life, at any rate) or show any other signs of onset. And even though this doesn’t necessarily clear me, it does make it a bit less likely. All in my family so far who were AD victims over the three generations have shown some sort of onset by age 45 with the notable exception of my grandfather and cousin Kay. They were both of somewhat indeterminable onset age, but didn’t die until their late 50s. So I can’t take too much comfort in the fact that I’m still symptom-free. I may simply be looking at a later onset than the majority of my affected family members.

However, sometime within the next few weeks I will know for sure. While at IU in November, in addition to acting as a “control” counterpart for my brother’s tests, I submitted my request to find out definitively if the family time bomb ticks for yours truly.

Michelle knows me so well. When I spoke to her on the phone from Indy about my decision to go ahead and find out, she completely agreed. I don’t know whether or not she was trying to lighten the mood, but she wasn’t laughing when she added, “You really do need to find out, because if you do have it, you’ve got a helluva lot of writing to do.”

Next: Not quite the “Road Trippin'” I had in mind
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