Thought Science Was Working Hard on a Cure For Alzheimer's?

Guess again...

The issue of Alzheimer's Disease is a bit personal for me. It runs in the family. In addition to the dismay of watching relatives decline with it, this also means that I’m at somewhat elevated risk of developing the disease myself. So, like many, I’d like to think that smart, objective scientists are working hard to develop rigorous treatments for the disease.

Apparently: nope. I’ve just finished reading Doctored: Fraud, Arrogance and Tragedy in the Quest to Cure Alzheimer's by Charles Piller. As one might guess from the title, it’s as depressing a read as you might want. Essentially, decades of research on Alzheimer's is down the drain and the outright perfidy of a surprisingly high number of scientists in this area has undoubtedly cost many people their cognition and lives.

According to the Alzheimer's Association, is the 6^th leading cause of death in the US, and about 1 in 9 elderly Americans will experience it. So, it’s kind of a big deal. About 3-4 billion dollars has been spent on Alzheimer’s research each year in recent years.

Despite all that effort one might notice the complete absence of effective preventative or treatment solutions for the disease. “Keep your brain busy and hope for luck,” seems to be the best advice the medical community has to offer.

Piller has uncovered why: Most of those billions of dollars spent on research were frittered away on a flawed theory of Alzheimer’s, specifically that it was caused by amyloid proteins and that removing those proteins might lead to a cure. To be fair, the theory wasn’t unreasonable: the development of amyloid plaques in the brain are characteristic of Alzheimer’s.

Of course, as they say, correlation doesn’t mean causation. We all say this, but do we ever really mean it? Not Alzheimer’s researchers apparently: they stuck to the theory despite treatment study after treatment study showing little evidence for effective amyloid-based interventions. The current standard of care (which isn’t super impressive in effectiveness) is a drug called Aricept…which was introduced in 1996, 30 years ago. Aricept can somewhat improve cognitive performance for people with mild to moderate dementia, but doesn’t otherwise slow or stop the disease¹. Since 1996…there’s been little other advance.

Part of the problem was that too much of the research was simply rubbish. Piller, in his investigations, uncovers a vast network of scholars publishing crap research, much of it fraudulent. There were numerous conflicts of interest: scholars fabricating research to push poor-quality, often dangerous medications that they stood to profit from.

Even scholars who weren’t directly involved in fraud apparently had blinkers on when it came to the amyloid hypothesis. This meant that the field refused to consider other theories of what might cause Alzheimer’s Disease and how to treat or even cure it.

There are few heroes in the story…even some of the whistleblowers have their own conflicts of interest (some of them short-stocking pharmaceutical companies with bad medicines). A few whistleblowers seemed more intent on the sheer joy of humiliating other human beings than on righting the science record, per se². Nonetheless, I don’t think there’s much doubt about the complete garbage field this area of research descended into. Even if we’re skeptical of some whistleblower motives, we need only look at the completely stalled Alzheimer’s treatment options to guess the book is basically correct.

What’s more depressing is I suspect this situation is true for much of medical science. After some significant advances in the 20^th century, medical (and social) science has largely stalled out. I’m not saying there aren’t some important advances, but the overall outlook for life isn’t a ton different than when I was a teen growing up in the 80s.

This makes me wonder just how much of medical science, like Alzheimer’s research, has descended into conflicts-of-interest, poor-quality studies, the tendency to report miniscule effects as clinically significant when they weren’t (something Piller explicitly notes, and something I’ve been shouting into the hurricane about for years³), and outright fraud. How many decades have been wasted; how many lives have been lost?

This current state of affairs also gives credence to Republican efforts to cut government funding for research. Why should taxpayers pay for fraud, after all? Even if Alzheimer’s research is an outlier in terms of fraud, so much of medical and social science is entirely lacking in even a hint of rigor. So, sure, Republicans have a point here…why are we paying top dollar for a dirty house its occupants refuse to clean?

I saw this literal bit of snark from academics more than once: “Republican cuts to science funding? Hope you didn’t want an Alzheimer’s cure!” What Alzheimer’s cure? That is the worst possible example you could give to counter Republican funding cuts. You’d be better off arguing for science funding to prove Pluto is a real planet after all, which I’d be all for. Or just take a wad of taxpayer dollars and set it on fire. Just don’t insult voters by pretending that social and medical science, as it devolved into the 21^st century, is capable of delivering on much of importance⁴.

I do hope medical researchers make some kind of concerted effort to clean that house⁵. I think we should fund medical science which is rigorous and robust, and we should fund that generously. Right now that’s not what’s on offer, mostly. Researchers can fix this by serious efforts to improve rigor and change the perverse incentive structures for academics that lead to p-hacking, overinterpretation of weak effect sizes, and outright fraud. But mostly what I’m hearing is defensiveness and empty promises of miracle cures somewhere around the corner if only we don’t turn the gravy train taps off.

1. Aricept is, weirdly, the hero of this story, product of a bigone era in science. It’s weird to say that as pretty much everyone acknowledges Aricept’s effectiveness is modest.

2. Some of this was enough to make me get nervous about false positives on the fraud detection side. Once people get overconfident and aggressive in their sense of righteousness, recklessness inevitably ensues.

3. I honestly don’t know what it’s going to take for scientists to realize just how much damage they have done both to the reputation of science but also in actual cost in human lives by their obsessive adherence to “every effect size is precious” arguments. Piller raises the example of one failed Alzheimer’s drug that was promoted as helpful, despite very weak effect sizes for utility coupled with potentially fatal side effects involving brain bleeding. But, sure, let’s just keep portraying those r = .06 effect sizes as meaningful.

4. Lest I paint with an irritated but too-broad brush, there do seem to be exceptions. Off the top of my head, vaccines for Ebola and Covid19 (albeit it’s effectivness was probably initially oversold to some degree), as well as new treatments for prostate cancer that limit the horrible side effects come to mind. But notice, it does take more thought than thinking of the remarkable advances of the 20th century.

To be clear too…I’m not making an anti-science argument. We need good science and should fund that generously. My concern is that the culture of academia has, itself, become anti-science and desperately needs reform.

5. Requiring preregistration for clinical trials has been one advance, but clearly not enough.