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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?

#81

Post by DANmode »

xattt wrote: post #38
ki4jgt wrote: post #21

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 ma…

Are recurrent childhood neglect and abuse events not an antecedent to mental health morbidity in adulthood, which then creates missed opportunities for growth and necessitates and the need for the use of medications? I think you’re making a giant leap from A to Z and missing a whole bunch in between.

Are those things not linked to cPTSD,

which is linked to nervous and endocrine dysfunction,

which is linked to Alzheimer’s/Dementia?

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

#82

Post by DANmode »

ki4jgt wrote: post #21

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 ma…

> your brain just gives out.

Meaning, failing of the glymphatic (and possibly lymphatic!) systems.

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

#83

Post by wonnage »

iwalton3 wrote: post #48

I have a kind of outlandish hypothesis that needs more research before it can be taken seriously, but it basically says that the cause and effect are backwards. Mental atrophy due to less learning/thinking, isolation, loss of meaning and purpose happens first. The sleep down regulation and decay of mental circuitry comes after. Would explain why treating the physical symptoms doesn't work. Protective against the prob…

This isn’t a hypothesis, it’s a wild unsubstantiated guess

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

#84

Post by stackghost »

ramraj07 wrote: post #77
bsder wrote: post #65

Earlier quoted context omitted.

There is a LOT of causal data. Autopsies of brains of Alzheimer's patients were rife with amyloid. People with mutations that caused amyloid got Alzheimer's earlier than others. The hypothesis didn't come from nowhere. To contrast, look at how much trouble medicine has had treating brain tumors. It has taken a long time to get effective treatments for various reasons. And Alzheimer's is way less direct in cause/effec…

> Autopsies of brains of Alzheimer's patients were rife with amyloid Do you want think carefully about how this can possibly suggest this is a causal link? > People with mutations that caused amyloid got Alzheimer's earlier than others. People with mutations in those genes got a particular type of inherited alzheimers early, this says nothing about the cause of general Alzheimers.

This comment is so needlessly aggressive and argumentative. I hate this about HN

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

#85

Post by verisimi »

jleyank wrote: post #30

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 gues…

> Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable.

To be clearer, Pharma is chasing a nice long treatment plan, that will require expensive drugs till the end. Pharma does not heal - this is not good for business. So there are criteria around what they are searching for.

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

#86

Post by DANmode »

hcknwscommenter wrote: post #23
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.

How many of them have their lymphatic and glymphatic systems effectively halted by parking their bodies in a chair or being bedridden?

Even the most unwell person (in the US) is still dragging themselves to the store and work, on average.

Simple, brief movement that we often relieve the elderly of is the pump that actions the lymphatic system.

Being older brings its own additions to the table.

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

#87

Post by uecker »

t-3 wrote: post #78
UberFly wrote: post #73

Earlier quoted context omitted.

The peer review process was repeatedly cheated by self-serving fraud. The medical field requires honest results and reporting. Why are you defending the fraud?

Science is no longer a hobby for the idle rich, it's an occupation. Peer review cannot function in a hostile environment governed by self interest (results == resume). Science practice needs to adapt to modern conditions rather than to pretend the idealized system that worked for an exclusive and elite group would work for a competetive worldwide industry.

This is exaggerating and generalizing too much. Science still works extremely well in general.

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

#88

Post by [deleted] »

stackghost wrote: post #84
ramraj07 wrote: post #77

Earlier quoted context omitted.

> Autopsies of brains of Alzheimer's patients were rife with amyloid Do you want think carefully about how this can possibly suggest this is a causal link? > People with mutations that caused amyloid got Alzheimer's earlier than others. People with mutations in those genes got a particular type of inherited alzheimers early, this says nothing about the cause of general Alzheimers.

This comment is so needlessly aggressive and argumentative. I hate this about HN

[deleted]

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

#89

Post by bsder »

ramraj07 wrote: post #77
bsder wrote: post #65

Earlier quoted context omitted.

There is a LOT of causal data. Autopsies of brains of Alzheimer's patients were rife with amyloid. People with mutations that caused amyloid got Alzheimer's earlier than others. The hypothesis didn't come from nowhere. To contrast, look at how much trouble medicine has had treating brain tumors. It has taken a long time to get effective treatments for various reasons. And Alzheimer's is way less direct in cause/effec…

> Autopsies of brains of Alzheimer's patients were rife with amyloid Do you want think carefully about how this can possibly suggest this is a causal link? > People with mutations that caused amyloid got Alzheimer's earlier than others. People with mutations in those genes got a particular type of inherited alzheimers early, this says nothing about the cause of general Alzheimers.

> People with mutations in those genes got a particular type of inherited alzheimers early, this says nothing about the cause of general Alzheimers.

This is completely analogous to claiming that people with mutations in BRCA (which causes a lot of early breast cancers) says nothing about general "cancer".

That's simply flat-out wrong. Genetic mutations like BRCA affect certain subsystems and many of those subsystems are common and relevant to many different cancers outside of breast cancer or breast cancers that appear later. Lots and lots of cancer research proceeded by studying the common systems that BRCA affects. Sure, those subsystems aren't involved in every cancer, but they're involved in a solid chunk of them.

And, even better, when you find one that isn't affected by one of those subsystems that BRCA touches, that's an interesting result, too. Now you can look at what the differences are, figure out what the new subsystems are and categorize your cancer more specifically which makes successful treatment more likely.

There is absolutely no reason to believe that Alzheimer's is any different on that front.

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

#90

Post by hn_throwaway_99 »

I'm surprised there was no mention (at least none that I found when searching) of the relatively recent research coming out of Harvard regarding the hypothesis that low levels of lithium in the brain are responsible for a lot of Alzheimer's cases.

The research is still in the very early stages (largely mouse models, though they did develop the hypothesis by looking at differences in human brain tissue post mortem), but to me my biggest fear is that little research will be done because the "cure" is a commonly available, non-patentable supplement, lithium orotate.

As someone in middle age with a family history of dementia, I've decided to start taking lithium orotate because the risk/reward profile looks so good from my perspective. Lithium orotate has been sold as a supplement for decades, and at those levels it is very safe with extremely-small-to-no chance of adverse effects (e.g. https://www.sciencedirect.com/science/article/pii/S027323002...), so I figure the worst that can happen is I'm wasting my money, but I'd take that for even the small chance that it helps ward off dementia.

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