The plot continues to thicken...

Chronic Traumatic Encephalopathy (CTE) is the name researchers have given to the pathological changes associated with repeated blows to the head, e.g. those from playing in the National Football League.  In the news today are the results of a post-mortem analysis of 26 year-old Chris Henry's brain.  Henry, who died in what was deemed an accident -- falling out of a moving pick-up truck during a domestic dispute, was said to have the tangles and plaques deemed pathognomonic for CTE.  At some point, the NFL will properly explore this and more fully fund research into it.  Until then, the Super Bowls and Sunday NFL marathons will continue.  You know, the band kept playing on the Titanic too.

[Also, I'd be curious as to what the brains of other football (a.k.a. "soccer") players look like.  "Headers" don't seem like benign meetings of the cranium and ball to me...something my mother worried mightily about when my sisters and I used to play organized soccer in our youth.]

Alzheimer’s and the NYTimes revisited

Chuck C highlighted a NYTimes article about familial Alzheimer’s Disease (AD). Today I read a NYTimes article about the use of PET probes to identify AD.

Familial AD has guided current thinking re. the pathophysiology of AD: i.e. the role of amyloid plaques. The three genes implicated are amyloid precursor protein (APP) and presenilin 1 and 2. It is hypothesized that amyloid beta proteins (in particular aβ42) aggregate – and to make a long and complicated and continuously changing story short – cause inflammation and havoc that results in neuron loss. The cortical and subcortical neuron loss manifests as cognitive impairment and dementia, which are the basis for the clinical diagnosis.

Clinical diagnoses are imperfect. The push for markers is strong and lucrative. The NYTimes article that I mentioned earlier highlights the work of Daniel Skovronsky (who is an MD, PhD in industry) and the development of a F18 PET probe targeted against amyloid plaques. In short, the probe identified amyloid plaques that were confirmed in post-mortem autopsies. The work is a technical advancement over the prior C11 amyloid probe. I don’t know the probe’s sensitivity or specificity. And remember that the gold standard is a post-mortem autopsy staining for amyloid plaques.

Amyloid plaques may not be the whole story, though. Transgenic mice that express “abundant” amyloid plaques did not show a strong correlation with neuron loss, in particular the hippocampus. Individuals vaccinated against aβ42 cleared amyloid plaques, but the effects did not protect against neurodegeneration. Other hypothesized processes include i) hyper-phosphorylated tau mediating the formation of neurofibrillary tangles, ii) a decrease in acetylcholine synthesis, and iii) the loss of locus ceruleus neurons that synthesize norepinephrine. The complicated picture correlates with the current understanding of most AD cases, which are sporadic. Out of the many genes screened for associations with sporadic AD, APOE4 is the strongest risk factor. There are probably many more unknown protective and risk factors.

Skovronsky’s probe and other probes (including the ones tested here at UCLA) are baby steps in the right direction. Non-invasive, laboratory diagnostic tests are the holy grail of neurological and psychiatric diseases. And besides their diagnostic applications, in-vivo imagining has the potential to delineate amyloid and tau’s contributions toward the pathology and progression of AD. The NYTimes article states that “20 percent of people over 60 with normal memories had plaque”; these patients “were still statistically in the normal range,” and they “did worse on every memory test than the control group.” What does this mean? I smell longer studies.

But even more lucrative than diagnostic tests are pharmacological treatments. Acetylcholine esterase inhibitors (e.g. donepezil) and NMDA agonists (e.g. memantine) are symptomatic treatments only. I imagine pharmaceuticals have been salivating for some time… Meanwhile, the basic science must continue! Here is some bed-time reading.

Why Medicine?

It is personal statement season, and 2011 med school applicants are faced with the daunting task of answering the question, "Why do you want to go to medical school?"

Tough question to answer in 5300 characters or fewer.  Not sure I ever wrote a good personal statement, or that I could in the future.  Two years from now I will have to, for residency.

Something to look forward to.

And then there's always the wisdom of this guy, talking to graduates at Stanford recently.  If you acknowledge that the practice of medicine needs to, and is, changing, maybe the field is for you.  Or maybe it is not.

Paper writing...

...tires me out.  So does thinking about this.  And this.

A health plan, 2 bucks a year

I'm not passing judgment one way or another about Rwanda's national health plan, but it strikes me as a positive start and model for health care in developing African nations.  It's interesting how some basic and dirt cheap measures are apparently  improving outcomes for Rwandans...

When the “Step One Adventure” (SOA) began...

... I considered posting updates, which sounded like a good idea, i.e. until I realized that most of my writing would be filled with angst and more angst. A little time has provided an emotional buffer, and I feel a somewhat comfortable providing commentary.

If you’ve taken SO, you know what I am talking about. If you plan on taking SO, you will soon. For everyone else, don’t worry: you aren’t missing out. Here are the cliff notes.

In a tiny little carrel on the eight floor of a building called “the Stacks,” I spent most of my day reading through “First Aid,” “BRS Pathology,” and “Rapid Review Pathology,” while doing USMLE World questions. Midway through my studying, I fled the stacks for my parent’s home. I drank better coffee, ate home-cooked meals, finished a first pass of the material, and started to make some headway on the Q-bank. When I returned to West LA, I avoided the stacks. My room became my cave. The days were spent hunched-over in front my computer, doing questions, questions, and more questions until I developed UWorld-burnout to go along with First-Aid-burnout. I tweak my back from poor posture; I developed a mild fungal infection on my left elbow. At this point my body hated me and I was ready to get the SOA over with.

There were times during the process when evil little thoughts tempted me to postpone my test date. “Anthony, you could do better if you had an extra week.” “Anthony, there is so much more high yield material to go over.” Now that I’ve taken the exam, I could not imagine the unnecessary suffering I would have put myself through. I accepted the gaps in my knowledge. And as Chuck C told me, I had to “trust the preparation.”

The preparation was both hellish and useful. The experience forced me to work really hard for a substantial amount of time. And while I worked hard, I tried harder to keep sight of the bigger picture: life will go on after the test. The SOA wasn’t fun, but there people out there who are having much less fun all the time. Let’s count our blessings, folks.

Alzheimer Disease - "earlyonset" and new therapies

NYTimes has a popular piece about an extended family, ravaged by early-onset (earlyonset) Alzheimer Disease and how a study using vaccines and anti-amyloidogenic medications is attempting to see whether early interventions might affect disease course.  Given how difficult the disease has been to treat thus far, I'm not terribly optimistic about the current studies.  But in order to get to the promised land of developing treatments that dramatically affect outcomes, sometimes the best researchers can do is continue to soldier on.  At the very least, new insights are sure to emerge...