Wednesday, 30 July 2014

Losing a Step?



There is a common expression one hears about professional athletes as they age - "he's lost a step."  The meaning typically indicates that a player, due to advancing age, is just a bit slower than he used to be in his prime, and thus can no longer make a play he was once able to convert in his younger days.  The only sport with which I would say I have a degree of fluency with is baseball, and the most frequent occurrence in this context is about a fielder who fails to catch a ball - a centre fielder who charges back after a fly over his head that just eludes his glove.  "Devon White has lost a step; a couple of years ago, he would have had that double."  I presume the same sort of phenomenon exists in basketball or football.

A couple of things have collided these past few days that have made the idea a bit more personal.

The first is, this morning, as I was preparing for work, it took three attempts for me to properly tie my necktie.  Some days, I wear a bow tie, which ties more or less as a shoelace, so it's pretty much an auto-pilot sort of deal.  Most days, I wear a standard tie, and use a Windsor knot; it's basic, and simple mechanically to execute.

For some reason, this morning, I could not seem to get the knot done.  It wasn't a problem that one end of the tie was too long or too short, or that the knot was sloppy.  The basic mechanics momentarily escaped me, and I had to pause, think for a few seconds, and after the third failure, concentrate on the mechanics ("the rabbit goes round the tree, finds the rabbit hole....") 

It seems like just one of those little things that happen when we are distracted.  You miss the freeway exit, or add sugar to your coffee twice (or not at all).  No big deal.  And I am reasonably assured this incident doesn't really signify any calamity.

But it did give me pause.  

Have I lost a step?

My son, nearly nine years old, at times likes to joke about dad's "Alzheimer's disease." He is parrotting the comments of his mom, who will tease me when I forget where I've left my glasses, or a book, or ask the same question twice.

I am closing in on 45 years old, and it's extremely unlikely of course, that I actually am exhibiting Alzheimer's symptoms.  

Still.  

I am a reasearcher working in pharmaceutical development, and have spent significant time over the past few years researching Alzheimer's disease.  I am familiar with the current state of the science with respect to the aetiology, treatment options (more to the point, the lack of them), the struggles to diagnose patients - particularly early patients.

One of the challenges in AD research, one that has bedevilled efforts to effectively treat patients, is the ability to identify who is an AD patient at the early stages of the disease, prior to significant brain loss.  AD is much more than the familiar symptoms of memory loss - it is marked by atrophy of regions of the brain, often beginning, it is thought, with the hippocampus.  This loss accelerates, resulting in loss of memory, executive function, physical function, personality, and ultimately death.  Currently, treatment can only begin when mild to moderate AD has set in - patients begin to exhibit significant cognitive impairment.  It is widely believed that treatment thus cannot restore lost brain tissue, and thus attempts to inhibit the disease at this stage are doomed before they start.

There is a staggering battlefield of failed clinical trials to back this up.

AD exists within a constellation of dementias - Lewy Body, atypical, AD among them - and each is marked by different aetiologies, trajectories, and potential treatment.  All are marked early on by what is called "mild cognitive impairment" (MCI).  The question though is, how to differentiate among the types, and what MCI is true pathology versus just memory loss associated with advancing age.

I've worked with Bruno DuBois and Howard Feldman, two researchers who have been central at setting up criteria for defining AD and MCI.  My world is non-clinical, so among the items I bring to the discussion is evaluating the performance of diagnostic criteria.  There are questions of "sensitivity" (are we able to identify correctly all patients who may have the disease - the false negatives), "specificity" (are we able to differentiate those who have the disease from those who do not - the false positives), positive and negative predictive value, and ROC analysis.

The task is not trivial.  But the early indications of MCI that correlate with risk of eventual progression to AD (they are "sensitive") are early loss of executive function - can the person adapt behaviour to potentially changing stimuli - and word finding, using cues if necessary.  One of the best tests among these is the MoCA (Montreal Cognitive Assessement), which has demonstrated good sensitivity, but mediocre specificity.

Executive function can heuristically be thought of as the ability to complete a series of tasks when the expected sequence is disrupted.  I ride the train to and from work every day.  It's one of those "autopilot" things - I do not even think about it.  Get on the train; wait two stops.  Get off the train and on another...  But what if the train, due to construction, traffic, an incident avec un voyageur malade skips over my station?  What if I miss my stop?  With impaired executive function, it becomes difficult for someone to think: "get off at the next station, cross the platform.  Get on a train going back.

Tying a neck tie is not exactly executive function, but it is a relatively complex set of progressive tasks, and it is a bit irritating that I had to focus on the steps.  There are items on the MoCA more or less parallel to a mechanical sequence like this, and today, I failed them.

I've felt recently an increase in incidents where I just can't quite find the exact word I want.  It has always happened of course, but I find it happening more frequently at 45 than it did at 40.  Just yesterday, I wanted to use the word "ostensibly," but could not for the life of me remember it until several minutes later.  I ussed a different word in the discussion - not the precise word I wanted, but close enough.  As an aside, one of the tests for MCI is the Free-Cued Selective Reminding Test, pieces of which are also incorporated in the MoCA.  

Part of the problem of course could be that I now live in a Francophone world, where English does not predominate, and thus it's just the case that certain fringe words (is 'ostensible' a fringe word?) are just not going to be exercised as often.

Still, I plainly have lost a step.

I'm sure that at 45, I do not actually have symptoms of Alzheimer's disease, but it does give me pause.  
Devon White ultimately lost enough steps that he could no longer play centre field, and was moved to a far less-demanding position.  In left, he remained an outstanding fielder - far better than the typical left fielder, who often is a lumbering huld with a poor arm (think: Pete Incaviglia) whose bat is needed in the lineup.




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