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Why has there been so little progress on Alzheimer's disease?

freakonomics.com

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Re: Why has there been so little progress on Alzheimer's disease?

#21

Post by ki4jgt »

Type-3 diabetes? It's degraded endocrine and cardiovascular functionality. Basically, your enzymes stop producing -- things like testosterone and insulin. Your lungs stop working as efficiently, and your brain just gives out.

If you're looking to beat type-3 diabetes, you need to have a daily routine of exercise while you're young to keep these systems in shape when you're old.

You also don't need to belong to any marginalized groups, as ACEs tend to wear your body out over time -- breathing, kidneys, and heart in particular. People with traumatic childhoods (bullying, abusive parents, etc) have a huge risk of dying of dementia -- if their kidneys don't give out first.

Re: Why has there been so little progress on Alzheimer's disease?

#23

Post by hcknwscommenter »

sublinear wrote: post #11

I'm not saying I'm the best informed on this topic, but I thought the root cause has been known for a long time now as degraded endocrine and cardiovascular function. That's also why Alzheimer's can take so long to develop. It's just one aspect that we've chosen to focus on because it's more clearly noticeable, but it cannot easily be treated in isolation from everything else. If it was, it would regress quickly with…

We truly do not know the root cause. There are plenty of folks with "degraded" endocrine, cardiovascular, and both systems. Most of them do not develop Alzheimer's.

Re: Why has there been so little progress on Alzheimer's disease?

#24

Post by levocardia »

hx8 wrote: post #16
readthenotes1 wrote: post #3

"One possibility: a leading hypothesis pursued by researchers (and funders) was built on science that now appears to be fraudulent." Possibly the most likely possibility?

There are multiple factors, but the one that contributes the most is that it's actually a very challenging disease to study and improve on. 1. It acts on the brain, one of the organs we understand the least. 2. It's relatively slow acting, and easy to miss in the early stages. 3. It impacts the older population which will have confounding health factors. 4. It doesn't fit neatly into a big category we already know a…

Elaborating a bit - brain is hard to study since you can't easily take a biopsy of it (from a living person at least), and various brain scans are not great at identifying the stuff we care about.

The slow acting nature of it means also you have to wait a long time to see results of clinical trials; also because early stages are easy to miss that also means you are stuck studying people who are already pretty senile and thus might be beyond the point where you can make a big difference.

Ruxandra has a nice piece, focused on cancer, but the reasoning is basically the same here: biology is just really hard. Sometimes we get lucky but in general it's a long, slow slog.

[1] https://www.writingruxandrabio.com/p/why-havent-biologists-c...

Re: Why has there been so little progress on Alzheimer's disease?

#26

Post by hcknwscommenter »

hx8 wrote: post #16
readthenotes1 wrote: post #3

"One possibility: a leading hypothesis pursued by researchers (and funders) was built on science that now appears to be fraudulent." Possibly the most likely possibility?

There are multiple factors, but the one that contributes the most is that it's actually a very challenging disease to study and improve on. 1. It acts on the brain, one of the organs we understand the least. 2. It's relatively slow acting, and easy to miss in the early stages. 3. It impacts the older population which will have confounding health factors. 4. It doesn't fit neatly into a big category we already know a…

You can't definitively diagnose it without an autopsy of the brain.

Re: Why has there been so little progress on Alzheimer's disease?

#27

Post by darth_avocado »

panabee wrote: post #13

TLDR: gatekeepers stifled exploration and innovation. When a topic only has a limited number of experts, those experts become gatekeepers. Those gatekeepers directly or indirectly control research funding. Gatekeepers necessarily harbor biases, some right and some wrong, about how the field should progress. For Alzheimer's, some gatekeepers were conflicted and potentially directed the field in the wrong direction. On…

[dead]

Re: Why has there been so little progress on Alzheimer's disease?

#28

Post by panabee »

manquer wrote: post #20
panabee wrote: post #13

TLDR: gatekeepers stifled exploration and innovation. When a topic only has a limited number of experts, those experts become gatekeepers. Those gatekeepers directly or indirectly control research funding. Gatekeepers necessarily harbor biases, some right and some wrong, about how the field should progress. For Alzheimer's, some gatekeepers were conflicted and potentially directed the field in the wrong direction. On…

> gatekeepers directly or indirectly control research funding. Perhaps funding like public grants could be controlled by few? Should not the case for private money? Relatively common health issues older people tend to get fair amount of private funding after all. Rich people tend to be older and they are lot more likely to see amongst their friends and family Alzheimer's and Parkison's or even cancer and so forth and…

If you're a wealthy person lacking a neurobiology background, how do you decide which research efforts are the most promising? Which labs do you back?

Generally, you rely on experts.

Who typically became experts by adhering to the conventional wisdom set by gatekeepers.

"Science advances one funeral at a time" feels apt.

Sadly, the problem isn't confined to Alzheimer's.

Whenever only a few people decide what is "right," the same pattern of stifled innovation will generally manifest itself not by design or from malice, but because it's hard for a small group to be 100% right on what works and what doesn't -- especially on matters as inscrutable as neuroimmune diseases.

Re: Why has there been so little progress on Alzheimer's disease?

#30

Post by jleyank »

They had a biological model. They had multiple drugs that were showed activity against that model, and effectiveness in humans. Problem was, the model was wrong. Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable.

Whether it was fraudulent or just incorrect is a different question. We don’t know all of the details of human biology. We don’t even know what all we don’t know. Most guesses work to some degree to keep pharma alive - otherwise nobody would fund the business.

Edit: Google the in the pipeline blog. This and other have discussed this at length.

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