This article soars from hope to hype to skepticism. I guess that's a consequence of reporting on the fringes of science.

In particular, I wish there was more detail on the 100-cohort study where patients experienced "modest improvements" and how that's calculated. Is that average increase of X points on an MMSE, etc.

In my experience in my family, dementia is not a linear slide. My 85yo mother with Alzheimer's will sometimes present very well and you have to really get into conversational details to notice the dementia. On other days, she'll pick up a paperback and try to use it as a phone. Some days she's steady on her feet, some days coordinating all of those muscles is just too much.

Over the course of a couple years, you can track the decline, but it's not a straight line. "Modest improvements" makes me concerned that they measured a valley to a peak. It's only 6 months since the 100-cohort study.

You can click through the reference in the article, the full text of the paper is free:

> The mean MMSE score change were 1.6 at 48 hours (95% CI: 1.079 to 2.158; p < 0.001), 1.25 at 1 month (95% CI: 0.603 to 1.888; p < 0.001), 1.17 at 3 months (95% CI: 0.343 to 2.01; p = 0.004), 1.28 at 6 months (95% CI: 0.311 to 2.344; p = 0.016) after surgery

As an ML engineer, I improve models through trial and error. Sometimes a change improves my metrics, and other times it makes them worse, and I just revert it and try something else. It's scary to think about neurological surgery making progress in a similar way. We may not have a good theoretical understanding of why a procedure works, but we observe positive outcomes in a small number of patients and then start looking into expanding its use. It reminds me of procedures where doctors sever connections between the two hemispheres of the brain to reduce seizures. I've heard they can reduce symptoms, but disrupting connections in the brain can also have unexpected consequences. I hope we can do better than essentially throwing spaghetti at the wall.

to prevent this "scary" feeling the government should simply mandate that all treatment be done according to set practices never to be deviated from

As another MLE who has seen family members go through the disease, I will say the baseline is already pretty bad. So while it would be great to have a complete theory before administering treatments, if it works I’ll take it.

The theory always falls short anyway, that would be Plato's charge against Aristotle, if he could have one, that the purpose of philosophy is primarily critique, but understanding material processes involves actually working at it, so there is no need to have a formal notion of things so long as you have the capacity to interrogate them.

We still don't have much of a theoretical understanding of many things in medicine and healthcare, or have since learned that what we thought was a theoretical understanding is grossly wrong. Usually, the only way we can get any closer to such an understanding is by performing what are essentially experiments on people and seeing what happens, particularly people already suffering from horrific diseases and injuries. It may be disturbing and scary in some ways, but that's how things work.

I wish medicine were more like theoretical physics. I understand that it’d be difficult to come up with theories that could fully explain complex brain functions and diseases like Alzheimer’s. It’s also difficult to test those theories safely without crossing ethical boundaries. Being either overly cautious or overly optimistic could lead to bad outcomes. It seems like we need a reasonable balance.

Derek Lowe's post on this: https://www.science.org/content/blog-post/new-alzheimer-s-th...

I like Lowe but his post doesn't add anything to the discussion unfortunately.

The problem with this stuff is (as the article mentions) is that it’s going to take a while to figure out whether any benefit is just temporary.

I would guess that there are a lot of variables to eliminate too - eg is it possible that just having a surgery and recovering from anaesthesia can yield some of these benefits in some circumstances? Given that we don’t really understand how most inhaled anaesthetics fully work

Yes, indeed.

I've witnessed dementia patients take a fall, and then be dramatically more confused the next couple days. I've also seen them get some kind of social exposure, sunshine, exercise, etc. and present better for several days afterwards. Measuring "how well is the mind working" isn't like reading a digital meter.

re. sunlight, pharmacological immunomodulation via UV isomerization of a substance found on skin is… interesting imo: https://www.pnas.org/doi/10.1073/pnas.0603119103

If anesthetics cured Alzheimer's temporarily then any surgery would get the same effect and we would already know about it.

Firstly it’s not curing anything, it’s yielding some improvement. But secondly: what surgeries are performed on people with Alzheimer’s disease, let alone ones where cognitive improvement is even going to be monitored or noticed afterwards? (and even if it were noticed: periods of lucidity are not rare. It would probably be ignored)

It seems like you're arguing with this guy for the sake of argument. If anesthetics "yielded some improvement" in Alzheimer's temporarily then any surgery would get the same effect and we would already know about it. And what is the second point you are trying to make here - that zero surgeries are ever performed annually on Alzheimer's patients for any reason? And of the ones that are, the family wouldn't notice the dramatic cognitive improvement shown in this article, but they noticed it here?

I was not trying to say anaesthetics are actually the cure, it’s an example of the kind of elimination that has to be done to prove something is actually effective.

Look up how double blind tests are done on things that involve surgeries (eg implants)

> And of the ones that are, the family wouldn't notice the dramatic cognitive improvement shown in this article, but they noticed it here?

Because they’re primed to look for that improvement because they’re told that is the expected outcome

> Firstly it’s not curing anything, it’s yielding some improvement

It did cure some people, it yielded some improvements on average but it did yield extreme improvements in some people. That part isn't controversial.

> (and even if it were noticed: periods of lucidity are not rare. It would probably be ignored)

A year of being able to walk and talk normally when a patient could barely function at all would be noticed for sure.

> It did cure some people

Cure has a very specific definition. I don't think it applies here.

It would indicate that there is a circulatory issue in general that causes this. If so, there may be other blockages as well, at various other lymph nodes that connect to the brain, which would explain why it works better for some and not others. If you have multiple blockages this may only offer partial relief. As for what causes the blockages, my suspicion would be microplastics.

Cure means permanent. If the extreme improvements are temporary (yet to be seen) its not a cure.

I agree. Very likely to be brushed off as "you're having a good day today" unless you are looking for it.

If you have the money for the surgery, an extra year of cognition is huge. Short-term quality of life improvements are totally worth it if you can afford it.

(Disclaimer: the non-paywalled part of the article did not mention side-effects or complications of the treatment so I don’t know what they are.)

All benefits are temporary, my online friend.

Even if it is temporary, so what? Can't you just repeat it? And wouldn't clearing these drainage channels be harmless (modulo risks of any surgery) even if the theory didn't pan out? If I had early-stage Alzheimer's I'd go to the ends of the Earth and do everything I could to slow it down.

Repeat it? It's not removing a tumor. It's adding a path between lymph nodes and blood vessels. You can't just repeat that. After the surgery that path exists. It's a permanent functional change.

If some drainage good, maybe more drainage better?

Sounds like a good topic for research!

> Can't you just repeat it?

I wouldn't assume you could. I guess that's why people study these things.

Does it matter if it's just temporary? If it works, it is the smoking gun of what alzheimers is and why it happens. If it is not a permanent fix, the next question is what is happening in the body that is causing these blockages. It also means that microplastics may be a leading cause.

Most likely the build up of those beta amyloid is faster than what the brain can clear by itself. The drainage likely just reduced the amyloid significant enough for the brain to recover. This is likely more of physics explanation than biological. It is similar cleaning the wound by itself has spectacular effect for recovery than you leave it cluttered with dirt and pus.

It would be great if it works out, but I believe this treatment has been suspended in China as there are mixed results (ie people have ended up worse).

Being from Scotland I'd trust an NHS evaluation more than random news reports.

But that would suggest that this cures some form of Alzheimer's but not all forms.

If your Alzheimer's is caused by poor drainage due to a one off blockage this would solve it completely, but if its due to something else this would probably just be temporary as the article notes.

> I believe this treatment has been suspended in China

And the surgeon is in prison according to the article.

For reasons that may have nothing to do with the topic at hand.

Alzheimer's is so devastating that I can't blame people for being willing to give it a go even if it's an experimental treatment.

The government shouldn't be in the business of telling people what they can do, or have done, to their own bodies.

Alzheimer's is tricky. The person who is consenting to the procedure may not be the person in the OR. And both parties are vulnerable to scams and snake oil. This procedure needs studies, so there's a clear rate of success we can understand and communicate.

Government absolutely should tell people what they could do to some degree - vulnerable people are very prone to being scammed.

The parent author probably works for big pharma and stands to lose from this surgery, so he's resorting to lies and suppression.

Unfortunately those devastating conditions are exactly where the grifters prey upon people. Some of the people pushing the treatments aren’t grifters in the traditional sense, but they are so invested in the idea of becoming famous for having cured a difficult disease that they lose objectivity and can’t admit when their treatment isn’t working.

There is a lot of history in this. Cancer and autism communities have fallen victim to these schemes as far back as those conditions have been recognized. Every year there is a new batch of researchers who claim they’ve found a cure but the government meanies are preventing them from curing the whole world. They generate a lot of false hope, take a lot of money from desperate patients, and then fade into obscurity after the communities realize nobody is actually getting cured by these treatments.

This happens in every condition where there is not yet a good medical treatment. Long COVID is a good example of a recent condition where hundreds of doctors have claimed to have invented new treatments. They generate a lot of headlines, collect a lot of money from desperate patients before everyone realizes the cure isn’t working, and then they abandon their cure like it never existed.

This is why governments regulate these things. If you assume all of the treatments might work, it seems cruel for governments to get in the way. If you look at the history of how this plays out, they almost never actually have any substance behind them. It’s almost 100% grift or researchers who can’t admit when they’re wrong.

The counterargument I heard recently is that what if doing something with your body ends up causing harm to others. E.g. you suddenly lose the ability to drive coherently. I agree everyone should do whatever they want, but if you drive drunk you're guilty because you should've known better, it's impossible to get a driver's license and not know you're not allowed to drive drunk. But if you do something experimental and are not aware you are no longer capable of driving, are you really at fault? And even if yes, is it that satisfying someone goes to jail considering maybe it would be better if a family of four in the other car is still alive.

Real life is more complicated.

We're not talking about a world that only has one law "you can do what you like with your own body".

Other laws still exist too.

Owning pillows is legal. Killing people is not legal. Just because owning a pillow is legal doesn't mean you can smother someone to death with it.

I would hope that someone diagnosed with a mental disorder such as Alzheimers would lose their drivers license (not sure if this is the case), but if they were subsequently cured and passed a new driving test, then would you have a problem with that?

I don't know why you're giving me the pillow example, when it's the exact thing I discuss. You know you are not supposed to drive drunk. You know a drug you get from the doctor has side effects, the doctor will warn you. Those things are enough for most people not to take their chances, for people stupid enough to drive drunk, throw the book at them.

You can throw the book at people taking any experimental drug that can have a gazillion side effects they have no clue about, but this doesn't help the people that might get killed because someone experimented with a cure, did not want to harm anyone but still did. People are not numbers, but real parts of the world and someone else's lives. Laws are there to keep people safe, but are just the last line of defense.

You can take both positions, but your argument is overly simplistic.

I've have no idea what point you are trying to make. You appear to be attacking some strawman position of your own making, but the lack of logic and connection to what is being discussed is so vague that it is honestly hard to tell.

I gave the pillow example because it clearly shows how ridiculous it is to link things like this together. Your arguing that people should be denied experimental Alzheimers surgery because (paraphrasing) "maybe they'll feel cured, but won't be, and will kill someone in a car accident" (WTF?!), is no different to arguing that people should not be allowed to buy pillows because they might use them to smother someone.

Making laws against killing or endangering others (driving impaired, etc) is fine and desirable. Using the need for such laws to apparently try to make a case for banning experimental surgery is absurd.

No, I specifically referenced side effects of taking medication. In this case experimental medication which means we don't even know what all the side effects are.

> The government shouldn't be in the business of telling people what they can do, or have done, to their own bodies.

But they absolutely should be in the business of licensing and controlling claims you make as a professional.

If you're someone who is performing this procedure and not making claims of medical benefits based on your license, I can see the arguments for allowing it. The flip side is you lose some of the legal protections you get as this is not a medically sanctioned procedure. Let the family sue you for the harm you may have caused and the department of justice arrest you for any lives that may be lost.

> as there are mixed results

Huh. You completely made that up. Where in the article does it say that? Here's the truth from the article:

> Last year, they restricted the procedure to more-formalized clinical research settings,

It is the hallmark of a lowlife to suppress research.

I didn't make it up, I found it in the articles explaining why the treatment had been suspended in China.

You need to think more.

You lie. Quote the evidence for your claim. I did for mine.

We are not naive. We know when there is a conflict of interest. The intent to suppress is obvious.

Some conspiracies are real. When money is involved, they are doubly so.

Even if you are right, you are using the tone of a conspiracist. You are this close to posting, "They don't want you to know!"

Maybe dial it back a bit? You can be firm in your opinions and have more success in convincing others if you avoid vaguely worded accusations and the like.

Some conspiracies are true. There are billions on the line. Why is it so hard to see?

You aren't helping your case. You type like someone who puts pictures up on their wall with red string between them.

I don't think a conspiracy is necessary here. Three factors are at play:

1) It needs research. That takes a long time. 2) If its successful and good, the effects need to be studied in patients for years to understand the long term impact 3) Capitalism is going to try and optimize for profit, not for welfare. Which is the point you are making, except... it's not conspiratorial. Capital absolutely is out in the open about this.

That is missing the point. The underlying biological mechanism is rock solid. Engineering is needed to make the procedure less invasive, and to do it well enough to produce results.

It won't help the underlying AD pathology, but it's a workaround to mitigate some of the harm. It should in principle work better if done early before large deposits form in the brain.

> Capitalism is going to try and optimize for profit

This in no way allows spreading falsities and FUD about competitive prospects. It is not excusable.

If the two points you've posted are true, point me to some replicated studies that say so.

No, you lie and provide nothing to this conversation.

Literally in the article which you clearly only skimmed and did not READ "Hong is now running his own trial in South Korea and says that he is finding the same spectacular gains in some individuals, although not in everyone."

That's very much mixed results.

Of course a filter is needed to determine the right candidates. It is so for any surgery. You have nothing original to add.

FTA: "anecdotally at least, several clinicians say they’ve heard from colleagues in China that the majority of individuals backslide within a year of surgery, echoing broader concerns that any gains might not last."

The surgery doesn't address the underlying Alzheimers pathology. It just buys time. It's like that with a cardiac bypass or coronary stent, yet no one questions their usefulness. It could be that the science of brain and neck stenting requires similar development. This only adds to the importance of developing experience with it.

I wonder what information we have on keeping this drainage system healthy before developing Alzheimer's.

It seems China is repeating similar mistakes the western world did in the 20th century (e.g. psychosurgery, very weak regulations). It's like watching a car seconds before crash and you can't do anything to stop it.

The article explicitly states:

> The rapid adoption, in the absence of hard evidence, prompted Chinese regulators to intervene. Last year, they restricted the procedure to more-formalized clinical research settings, rather than the ad hoc use that had proliferated previously. And Xie, the pioneer of the technique, has been in detention since September for undisclosed reasons.

There is probably also some benefit to being willing to let some harm come to patients in order to quickly determine if treatments are viable or not. Western medicine puts a premium on human life but development of treatments is certainly slowed by that ethos .

It puts a "premium" on life only because all those regulations were written with blood from those who can't defend themselves anymore as those same arguments were used back then as they are today.

Yes, obviously. Point still stands. There is benefit to the collective in sacrificing the few. It's abhorrent to western sensibilities but i bet the west would be happy to use the resulting research, just like previous times it has happened.

Western medicine has been lax on ethos and rigor in the past and we ended up exterminating and neutering large amounts of the population to 'keep the genetic heritage pure'. That is still a major traumatism that forces us to approach medicine with a very strong ethos.

> very weak regulations

Seems you missed out on 10-15 years of development. Regulation strictness these days rival western.

Lots of people look to be trying to cover up and unfairly suppress this treatment. I guess big pharma stands a lot to lose, and they work for them.

I favor trials, of course, but the ones suppressing it would rather just bury it.

Seems like this treatment is widely reported on and there's interest in running controlled trials to evaluate its actual success rate. It's shown up on HN a lot.

And honestly, caution is valuable here. People with Alzheimer's are extremely vulnerable. As are their loved ones. Ensuring it's got rigorous data so caregivers can understand the tradeoffs seems important. Surgery at an advanced age is risky, no matter what.

> Surgery at an advanced age is risky

For all we know, it might in the future be possible to do it less invasively, like how a cardiac stent is installed. For us to get there, we have to pursue it aggressively. Dwelling too much on the current paradigm seems more constricting than helpful. We need an engineering-focused wartime approach to accelerate it.

I know it sucks to wait. But it's irresponsible to open up everyone to surgery for an unproven technique.

Hanlon’s razor much?

Just how naive are you?

Flowers for Algernon

I believe it was a mistake to approve anti-amyloid drugs like Aducanumab. Big Pharma threatened to stop research on Alzheimer if they couldn't sell this drug and make bumper profits from it. The FDA should never allow itself to be blackmailed in this manner. If drugs don't show a clear improvement, not just the "slowing of the progression" of the disease (which is infinitely debatable and subject to manipulation), they should be rejected.

The amyloid theory is a dead end, a wild goose chase which has led to tunnel vision and wasted three decades of research into Alzheimer. We're essentially back to square one save for some interesting data that viruses may be involved.

This had led to desperate patients seeking help from charlatans and quacks like the one described in this article.

The ongoing charlatan is the FDA and big pharma for peddling drugs that don't work and even do damage like cause brain bleeds. As for the surgery, everyone knows it is experimental.

I wonder if there are multiple causes of Alzheimer’s, and the variability in outcome is due to the fact that the treatment only is fixing one root cause.

That said, if it turns out that a treatment for some Alzheimer’s is some kind of “brain fluid” dialysis, it would be an amazing breakthrough.

Probably

Most conditions are like that, particularly ones where the underlying cause is poorly understood. We see symptoms that lookalike and assume they all point to the same thing

My understanding is that Alzheimer’s was only truly diagnosable with an autopsy into the early 2000’s.

> some kind of “brain fluid” dialysis

i think fixing the plumbing there may be a treatment for a bunch of issues given that for example the whole volume of the cerebrospinal fluid is normally refreshed 3-4 times a day (imagine changing oil in your car engine 3-4 times a day :) - i.e. any hiccup in the plumbing (even a temporarily one and even in the healthy people like a bad sleeping position) and you already may get headache, etc. One can imagine that any chronic performance degradation of the plumbing may lead to a bunch of issues (similar to say what happens in any other organ/limb when blood or lymphatic flow is degraded)

Specifically for Alzheimer's - we do know about direct importance of that plumbing system here - poor sleep is well correlated with Alzheimer's as during deep slow-wave sleep, the brain's glymphatic system actively washes away metabolic waste and toxic proteins, including Alzheimer-related plaques while chronic sleep deprivation increases the buildup of toxic brain proteins like amyloid-beta and tau.

That Alzheimer's surgery brings up another very important and pretty fascinating aspect - not only the Alzheier's may be not permanently damaging the brain, we may speculate that various things we observe as age related brain degradation may be not actual brain cells/core degradation and instead similarly fixable issues of just some utilitarian subsystems.

Alzheimer's isn't one disease, it's a degenerative disease process.

If this works it will be buried so that the pharmaceutical industries can find a pill intervention, no doubt.

Have you seen how many users on this very forum have tried hard to bury it, presumably for the same reason you noted?

> Have you seen how many users on this very forum have tried hard to bury it

They aren't trying very hard, it's still on the front page and being discussed and read about.

It would explain problems with treating Alzheimers. Everybody is trying to stop the brain from generating trash that destroys it, which is probably impossible, instead of fixing the trash collection system, existence of we are barely aware of.

I remember hearing the doctor who (I think) discovered these drainage channels being interviewed, it’s super interesting:

https://youtu.be/yAqwXoUS7sE?si=Gs-EGJ_Xtkh9TG7R

If this is correct, it’s a new discovery that these channels exist at all

Here's a short video explaining the procedure: https://youtu.be/eRAyu7FWK-E

It would be funny if after looking for more complicated causes if much of the Alzheimer's problems were down to bad plumbing. Still I guess a lot of complicated machinery malfunctions if pipes are blocked or the cables are iffy.

Chinese authorities already debunked the theory and banned the procedure.

There was the Italian Dr. Paolo Zamboni that in 2008 promised a multiple sclerosis treatment with a surgery on the neck based on falsified data. European Neurological society uncovered the scandal.

It seems the neck attracts charlatans.