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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?

#231

Post by stanford_labrat »

hx8 wrote: post #18
robwwilliams wrote: post #8

Earlier quoted context omitted.

The focus is definitely on scientific fraud, but what makes the fraud so easy in this case is singing and selling the same song that the big teams are singing and selling. You can fly under the radar AND get funded, and if you are “lucky” become an ultra big shot like Masliah at NIA.

I don't buy the fraud explanation as the full explanation. Other areas of medicine (stem cell) has had bigger incidents of fraud on top of other major headwinds, and still has made more progress. Fraud is everywhere and we still move forward in most arenas.

The stem cell field is also quirky. IMO it is one of the most cutthroat, competitive, ruthless fields of life sciences that is new enough in history to still have a bunch of pioneers fighting to be the figurative Oppenheimer. One PI’s fraud is quickly detected and fought over.

Meanwhile the Alz and Neuro field as a whole are well established, and the amyloid hypothesis was a foundational theory taken as a fact. Any initial questioning of this and they would brand you as a lunatic.

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

#232

Post by deepsun »

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…

> We don’t know all of the details of human biology.

Tautology statement. "We don't know all the details of X" for any X.

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

#233

Post by jvanderbot »

deepsun wrote: post #232
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…

> We don’t know all of the details of human biology. Tautology statement. "We don't know all the details of X" for any X.

That is not a tautology. But you're right it's trivially true.

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

#234

Post by josh-wrale »

DANmode wrote: post #228
josh-wrale wrote: post #218

Earlier quoted context omitted.

Point stands.

So does the lack of a model for Alzheimer’s, and other chronic illnesses, that the consumer-facing medical industry prefers to dismiss.

I didn't argue a model beyond one cause.

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

#235

Post by [deleted] »

fn-mote wrote: post #167
Drupon wrote: post #108

Earlier quoted context omitted.

>I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer’s isn’t my field If anyone wants to know who wrote the article linked before wasting time reading it, there you go.

For you, simply listing the author of the post is enough to discard it. Not everyone is that well informed, so it would be helpful for you to add another sentence explaining why this author has no credibility with you.

[deleted]

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

#236

Post by slashdave »

One of the most important ingredients of a proposal for a drug development program is viability: is there a path to market. The issue with Alzheimer’s is that until recently there was no practical diagnostic test. Without a test, there is no way to run a clinical trial. No clinical trial means no drug approval. Research is halted before it even begins.

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

#237

Post by hn_throwaway_99 »

dannyw wrote: post #152
hn_throwaway_99 wrote: post #90

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), b…

I agree with your post and the well-studied safety of it in humans at appropriate doses :) but the study you linked is on rats; and so there’s probably another better study to link. I experiment and take a small number of less-commonly-known supplements and those kind of studies _in itself_ should never contribute to “it’s safe for humans”. Anecdata: my personal brain/body didn’t react too well to 1mg a day, I felt s…

To add some context on the study I linked - that particular study was only focused on understanding why, after decades of use by humans as a supplement, that lithium orotate has so rarely been reported in any cases of adverse effects (all the cases I could find were acute toxicity from taking way too much, like the 18 year old woman who took 18 capsules at once, and still only suffered nausea and some mild tremors). So that study found none of the effects on specific organ systems in rats that you often find in other substances that have higher rates of adverse effects.

My point being, if that was the only safety study done on a brand new substance, I'd agree with you, but the safety profile really boils down to the decades of human use as a supplement.

All that said, I totally agree that many more human studies are needed to determine the actual efficacy of lithium orotate in preventing or reversing dementia.

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

#238

Post by jvanderbot »

jhedwards wrote: post #193
bradley13 wrote: post #145

Earlier quoted context omitted.

Pretty clearly not. It would seem that beta amyloids correlate with Alzheimer's, but do not cause it. The problem us "consensus science". You could get funding to research beta amyloids, but not to research any competing hypotheses. It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic.

> It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic. I'm not sure I understand this. We've added hundreds of gigatons of carbon to the atmosphere. There's no mystery here, it's basic physics and chemistry that this will change things, and it's accepted that we don't know exactly _how_ things will change. The alternative:…

Yes I believe GP was focused on the catastrophe part. It's very likely correct that our CO2 emissions are warming the atmosphere ocean etc, but it's not clear that runaway warming is inevitable or that life or geology have feedback mechanisms that turn an exponential into an S curve. That is, after all, basically what natural selection tends to do. Turning the table again, even if there are corrective factors humans might have immense suffering before it stabilizes. So we don't know.

You didn't ask, but my opinion on it is that we'll probably stabilize on a cleaner energy source and find natural countermeasures when suffering ticks up. Any top down pressure to change things whole cloth seems doomed, no matter how benevolent. We're closed loop creatures.

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

#239

Post by CodeWriter23 »

rcxdude wrote: post #51
CodeWriter23 wrote: post #45

Earlier quoted context omitted.

Actual Scientists are calling it Type-3. But these are the same scientists that are actually reversing Type 2 diabetes without expensive drugs. Of course they exist outside the pharma narrative, and they don't have any uncurious attack dogs willing to defend their narrative-busting results.

>and they don't have any uncurious attack dogs willing to defend their narrative-busting results. Well, they seem to have some champions here...

¯\_(ツ)_/¯ Get curious

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

#240

Post by hn_throwaway_99 »

r0l1 wrote: post #148
hn_throwaway_99 wrote: post #90

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), b…

It’s actually quite simple: 1–5 mg lithium orotate, vitamin D, omega-3 from algae with high levels of polyphenols, a daily exercise routine, and good food—not the processed crap you often get in the US. My grandmother is 94 and still mentally so sharp that she amazes me every time. https://michael-nehls.de/

It's actually not "quite simple" at all, and I think there is a gulf of difference (often misunderstood) about taking supplements as a personal decision because there is low risk of harm, there is some preliminary evidence they may be helpful, and one can afford them, versus touting them with certainty as the cure to a whole host of ailments without sufficient evidence, which is usually what "wellness influencers" and people selling supplements and "health optimization" programs do.

My grandmother lived to 102 and was mentally sharp right up until she died. She also smoked daily into her 90s.

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