Arguing About Alzheimer's 
(July 13, 2021)

The most engrossing medical story of the last couple of weeks has to be the FDA approval of Aduhelm, the little medicine with the big price tag and even bigger questions about whether it works or not. An event like this one brings up a zillion possible topics for discussion, among them:

- Why is a medication that may or may not work being approved at all?

- Seeing that this medication will potentially cost Medicare up to $30 billion per year, which areas of patient care will the Medicare administration throw onto the chopping block in order to pay for it?

- Why is so much focus (in other words, money) being put into treatments for Alzheimer's disease ($5-$6 billion PER MEDICATION) when the only things that we know of to date that slow the onset and progression of dementia are lifestyle changes?

- We've spent over twenty years and umpteen billion dollars in the quest for a cure (not even a cure, really; simply an effective treatment) for Alzheimer's disease and come up with exactly zip. Maybe everyone is barking up the wrong research tree altogether? Should we examine the basic assumptions that we are making about it?

And finally

- In light of all this, maybe the way to go for an individual is simply to make some extra efforts to avoid getting Alzheimer's in the first place? (Ya think? Ha!)

Here's the controversy over Aduhelm in a nutshell. Even though only one of the studies done to test the efficacy of the drug found any improvement in the test patients, there WAS some measurable decrease in the size/number of lesions that you see in the brains of Alzheimer's patients (the neurofibrillary tangles, or amyloid plaques). So the FDA approved it anyway. Was this bold and insightful, or was it stupid?

It was stupid. And I will tell you why. It is stupid because in health and disease, structure does NOT automatically equal function. If anyone should know this by now, it's medical doctors, but somehow they just won't get it. Medicine continues to be obsessed with describing and then changing structure in the expectation that an improvement in function will follow. 

That last statement might sound a bit odd to you. After all, you shore up the foundations of buildings when they start to cave in (unless you live in Florida), don't you? And we set broken bones and stitch up open wounds. That's all fixing structure to fix function, right? Well, yes. So let me say this instead. When we're talking about the human body rather than an engineered structure, sometimes a change in that structure isn't especially meaningful. Unlike a bridge or a condominium complex, a person's body can function normally with some pretty abnormal structures. 

Something that looks odd when imaging someone's body MAY only reflect the measures that their body is taking to cope with a problem. That's what bone spurs are; a joint has become kind of wobbly, so your body is trying to fix it with a bit of extra bone. Scraping off that bit of bone rarely does a thing besides fatten the surgeon's wallet. A physical oddity may not appear normal but it's often there for a reason, whether or not we understand that reason, and taking it away is not necessarily going to fix the problem associated with it.

Here's another example. If you do spinal MRIs on a random bunch of people without back pain, you find out that very many of them have bulging and even ruptured spinal discs. Why don't they have any pain? Because structure does NOT equal function -- or in this case, a diseased disc doesn't mean that you are doomed to pain and nerve issues. 

Now if someone has back pain AND a bulging or ruptured disc, and you medicate them or chiropractic them or acupuncture them and their pain goes away -- their MRI will still look the same. That bulge will still be there. It's probably inflammation that was causing the pain. It certainly wasn't the compromised structure per se. If it was, they'd still have the original problem.

One more.  One of the most overused medical procedures out there is surgically "cleaning out" an arthritic knee. That single procedure has put more Buffys and Chads through college than you could shake a stick at. But it is essentially worthless clinically. Why, though? After all, you've made visible improvements in the appearance of a knee joint. But it still hurts and it will continue to deteriorate just as fast. Surgeons have been wondering about this little mystery for almost 20 years. They wonder about it every time they do one, because they're still doing them. Aspen doesn't give away free vacations, ya know.

In order to find candidates for new medications, pharmaceutical research like to find a "surrogate endpoint" for a disease and then fool around with that to see what they can come up with. The surrogate endpoint for Alzheimer's disease is the aforementioned neurofibrillary tangle. Logic tells us that a medication which reduces the number or size of those lesions may very well treat the symptoms of Alzheimer's disease as well. All well and good. The thing is, once you've tested that medication in real live Alzheimer's patients AND IT DOESN'T WORK, you bag it. You don't approve it and hope for the best. That's shameful.

So you see where I'm going with all this. Just because you see physical improvements in the brain does NOT necessarily mean that you'll see improvement in the disease they supposedly cause. You need clinical studies to establish THAT -- and so far, there really aren't any. And that is why there has been so much fuss over the approval of a very expensive medication which has, at best, minimal effect. Just, you know, in case you were wondering.

All of this brings me to the prize-winning question that I asked at the start of all this, which was, of course, "maybe the way to go for an individual is simply to avoid getting Alzheimer's in the first place".  Winner! Winner! Tofu Delight Dinner! For any individual at This Moment in Medicine, THIS is the most important question to be asking.

Ya worried about Alzheimer's? Follow good lifestyle advice and you'll delay its onset, possibly by a considerable amount of time, or maybe prevent it altogether. As well as doing a lot of other good things for yourself. That's what I'll go into next time.

--dr. diane holmes
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