[janeway]

“We have no cure. I don’t want to know.”

If astronomers announced that a large asteroid might strike Earth in twenty years, and that we currently had no way to deflect it, nobody would respond by saying, “Come back when you already have the rocket.” We would immediately build better telescopes to track it precisely, refine its trajectory models, and begin developing propulsion systems capable of interception. You do not wait for the cure before improving the measurement. You improve the measurement so that a cure becomes possible, targeted, and effective.

Medicine is no different. Refusing to improve early, probabilistic diagnosis because today’s treatments are modest confuses sequence with outcome. Breakthroughs do not emerge from vague labels and mixed populations. They emerge from precise, quantitative stratification that allows real effects to be seen. The danger is not that we measure too early. It is that we continue making irreversible clinical and research decisions using imprecise, binary classifications while biological insight and therapeutic tools are advancing rapidly. Building the probabilistic layer now is not premature. It is how we make future intervention feasible.

[dataflow]

This analogy has a rather fatal flaw, which is that we already know people who've gotten Alzheimer's, and we also know for a fact people will continue to fall victim to it, at a pretty predictable rate. i.e. the detection has already happened! Anyone who was waiting for a potential victim to appear before researching the cure already has all the reasons they need to research it. Detecting whom exactly the next victim is going to be isn't really going to change anything as far as researching a treatment or cure goes. (Unless the person is super important or popular or rich, I guess?)

This is absolutely nothing like the asteroid example, where knowing that anybody is going to fall victim to it would itself be news of astronomical proportions. Previously there was a high chance the event wouldn't happen, and now it seems likely it will, so that entirely change the calculus of your priorities.

This just completely destroys the analogy. (There are other reasons it doesn't fit too, but one is enough.)

[TechnicalVault]

The reason the test and actually knowing who is likely to develop the disease is useful is that we don't know enough about the early pre-symptomatic stages of Alzheimer's. A lot of research has been focused on purging the plaques which form in the late stages of the disease and thus failed because these seem to be symptomatic rather than causative. The false positives are also very interesting from a research point of view because if someone is testing positive for the disease but it's not progressing this may give us a clue about how to control it.

The other slightly sad fact is that is also quite likely that any curative treatment will need to be started before you start to show symptoms, because the brain has already lost a lot of it's resilience by then.

[ahazred8ta]

[testing positive for the disease but it's not progressing] -- Yes, exactly this. There are people with two copies of the bad APOE4 gene. 95% of them develop early-onset Alzheimer's in their 50s. The medical community is now very intensely studying the remaining 5% to find out what's causing them to NOT get sick.

[RiverStone]

Can you provide the source for the 95% figure?

[ahazred8ta]

Sloppy wording. -- Fortea (2024) -- Over 95% of people with two copies have amyloid beta in their cerebrospinal fluid. (not full-blown Alzheimers symptoms, just early detection)

https://www.theguardian.com/society/article/2024/may/06/scie...

[friendzis]

> Detecting whom exactly the next victim is going to be isn't really going to change anything as far as researching a treatment or cure goes.

Your reasoning relies heavily on this statement, which is only true if occurrence is entirely random, which is in most cases not true. A condition can easily mask the cause of the condition and then you have a confounder(-s) that you have no way of controlling. If you can build multiple strata with high risk ratios, you can find baseline similarities and differences in those groups. Early detection is highly important in knowing these confounders in the first place and then controlling for; and as GP mentions allows for more targeted research in treatment. Without this we could easily spend all the research effort on the effect (symptom) of a condition without even approaching treatment of the cause, i.e. prevention.

A very similar thing has happened with the infamous atherosclerotic plaques. AFAIK (correct me if you are aware of any evidence) there is currently no mechanistic model of how these atherosclerotic plaques form. Yet we spend so much effort in lowering the symptomatic side of increased cholesterol/LDL (which has well-known positives) even if there are known metabolic pathways for LDL increase, based entirely on correlational studies, when LDL is not even close to being the best predictor of cardiovascular conditions. LDL just happens to be easy to measure in a blood test and easy to control with oral medication.

[wongarsu]

And even if occurrence was random, there might be effects that can only be measured early on. By identifying patients before the onset of serious symptoms we can get a much more comprehensive medical history than by only looking once the symptoms are bad enough to make Alzheimer's obvious, or by monitoring large strata of the population in hopes of including enough future Alzheimer's patients in the sample

[dataflow]

Not to sound like an LLM, but what else can I say—you're absolutely right!

[sigmoid10]

Accurate detection in individuals is still important for testing any potential cure. Otherwise you can only do normal population studies over a very long time and pray that you didn't miss on any confounding variables. With this level of accuracy in diagnosing, you can do targeted testing.

[lopis]

While that is true, it doesn't change the sentiment behind “We have no cure. I don’t want to know.” if knowing the diagnosis doesn't help you personally. Sure you might have a sense of responsibility for mankind but you still know you can't do anything to save yourself.

With that said, lifestyle changes can slow down the onset of Alzheimer's, so knowing the diagnosis isn't totally useless.

[noduerme]

A lot of people have enough of a sense of responsibility to donate blood, or donate their organs.

I've long had the suspicion that much of what is called Alzheimers or dementia is some form of prion disease. This study doesn't show that, exactly, but it shows that abnormal proteins may be directly correlated.

So - and I'm not saying this is the case - but suppose that the abnormal proteins identified in this study could be transmitted by blood transfusions or organ transplants. Wouldn't that itself be enough for your diagnosis to help you personally not transmit those proteins to someone else?

If your attitude is that no one else in the world matters once you get a bad diagnosis, then nothing really mattered to you before. Other people are working day and night trying to cure you, so there's no cause for that level of nihilism. You may as well try to help from the vantage point you have.

[altruios]

> We have no cure. I don’t want to know.

This is an incredibly short sighted, fragile-ego protecting, selfish instinct.

Making plans while you are cognizant is valuable, and the sooner you know, the longer and better plans you can make. Making plans with friends and family should be done sooner than later with these kinds of things.

It absolutely helps to personally to know, but people avoid emotional pain like the plague. So they delay and delay and then the emotional pain is amplified anyway when things come to ahead. It really is better to rip that band-aid off sooner... I think.

[lopis]

Maybe it is, and I'm not saying that's how I think. I would prefer to know the diagnosis. But that's not necessarily how everyone, or even most people, would act. So what if this is fragile ego and selfish? Are people not allowed to be weak, selfish?

[mapt]

In a case like this, it is possible and even substantially likely that a "Cure" represents a treatment you can apply after an early, routine blood test but before clinically significant symptoms arise, to prevent damage from becoming significant enough to represent an illness.

Late-stage Alzheimers', if not every stage, is very likely going to involve microscopic-scale physical damage to brain tissue that is functionally irreversible.

Blowing up an asteroid after you can see it in the sky with your naked eye will not save you.

-------------

It is also possible that what we call "Alzheimers" is actually biochemically five different disorders with distinct etiologies that have the same endpoint, and that it turns out we can cure two of them. Differentiating conditions for a biomedical catch-all category would be essential; "How accurate you can get the tests" is inseparable from this process of definition.

[kozinc]

It may not change much as far as researching a treatment or cure goes, but it may help with other stuff, like being better prepared for the future, like organizing a health care worker or getting family members to help out or to look out for you, and other stuff, which you might not be able to do at a later stage of Alzheimers.

While there aren't any cures yet, certain treatments and lifestyle strategies may slow its progression, keep quality of life as long as possible and stuff like that for as long as possible. (And the sooner you start with that, the better)

[TaupeRanger]

More information is not always better for the patient. If you could detect the disease 5 years before symptoms began, there are certain psychological harms that come with that knowledge. These must be balanced against the things you mention about "slowing" the disease (unclear if any treatments do much for a given individual) and planning your future. You talk about quality of life, but quality of life declines the MOMENT you learn that you have a progressive, incurable, disease that will slowly rob you of your mind. It's not clear at all that knowing about your disease earlier is actually better for anyone.

[stvltvs]

I understand the concern about anxiety about their impending condition, but medical providers must not paternalistically decide to withhold a diagnosis from patients, at least not in all cases.

If I got an early diagnosis, it would motivate me to get my affairs in order to lessen the burden on my family and check off some bucket list items before it's too late. Don't rob me of that opportunity.

Before ordering the test, ask patients "If you were going to get Alzheimer's, would you want to know?"

[tim333]

>Detecting whom exactly the next victim is going to be isn't really going to change anything

What if you found for example all the diagnoses happened shortly after an HSV-1 infection? The more information as to what's going on the better, for research at any rate.

[KurSix]

It's less like discovering the asteroid exists, and more like refining its trajectory enough to know where and when to intercept it

[ransom1538]

Off topic: Would insurance companies carry patients after being detected for Alzheimers?

[soco]

In the US or in countries with working healthcare?

[MagicMoonlight]

If you know they’re going to have it twenty years early, then you can try out preventative treatments. You can look at causes. You can get them to put power of attorney in place and prepare for their future.

Why are you so furious about the idea of people knowing?

[TaupeRanger]

No one is furious, but it is well established in epidemiology that more knowledge is not necessarily better for the patient. There are psychological harms that occur from the moment you learn that you have a disease that will slowly rob you of your mind. In general, you want fewer harms in your life.

[AnimalMuppet]

You don't see any harm in a disease slowly robbing your mind, while you are not warned, and so you waste the time you have left?

[Spooky23]

Not really. Alzheimer's is about 60% of dementia, and is frequently misdiagnosed without a full workup. As primary care shifts to more poorly trained providers and doc in the box delivery models, you'll get less workups and more misdiagnoses.

A more objective blood test will make for more accurate diagnoses and and better treatment.

[jader201]

> “We have no cure. I don’t want to know.”

> If astronomers announced that a large asteroid might strike Earth in twenty years, and that we currently had no way to deflect it, nobody would respond by saying, “Come back when you already have the rocket.”

I don’t think the analogy fits, for a couple reasons.

1. People not wanting to know whether they have Alzheimer’s is because of the fear of a fate worse than death — living with Alzheimer’s.

2. People not wanting to know whether they have Alzheimer’s is not the same was not wanting a way to detect it. As you said, being able to measure it may help lead to a cure/treatment. I doubt people are against improving detection — they may just not want the detection to be applied personally.

[r0ze-at-hn]

Cure is the wrong word. Alzheimer’s can be best described as a failure of a system and "debris" accumulates faster than it can be "cleared". There are many moving parts and everyone is unique about the cause of their system failure.

Wrote up my current systems understanding here https://metamagic.substack.com/p/the-alzheimers-equation, but it makes clear why treatments that target only one variable are mathematically doomed to fail to work on everyone and why there will never be a single "cure". It explains without needing to read 10,000 papers why we keep getting research talking about treatment X helps in some, but not all cases or symptom Y is associated in some, but not all, etc.

[tsimionescu]

This is some personal opinion that I would bet the vast majority of Alzheimer's researchers would not actually agree with. The current consensus is that Alzheimer's is a particular disease, or a cluster of similar diseases.

I'm not saying your wrong, just that the level of confidence in your assertions is not warranted.

[r0ze-at-hn]

After spending years tracking through the genetics, conditions, lab work, research papers and seeing individuals years into the condition, this model is the best I have and explains everything I currently know. Why the cluster of conditions result in the same outcome, why some treatments help some folks, but not others.

But that is sort of the point of science, you take all the evidence you have and create a hypothesis and iterate as you get more evidence. If I find evidence that suggests something else then I will be happy to tweak or abandon this. My level of confidence comes from the existing evidence and lack of evidence otherwise.

[david-gpu]

You forming a personal opinion after years of interest in the subject is fine. You asserting that opinion as a fact is the problem.

It is a tale as old as time. See the story behind the term. ultracrepidarian: https://en.wiktionary.org/wiki/ultracrepidarian#English

[MarkusQ]

Versus https://en.wikipedia.org/wiki/Argument_from_authority

See also: https://www.science.org/content/article/potential-fabricatio...

Amateur's asserting their opinions as facts isn't great, but epistemologically it's no worse (and systemically, like less harmful) than when the experts do it.

[foobiekr]

I want to know so that I can make plans. Including end of life plans, in all senses.

[iamflimflam1]

Exactly - there are things that I would change now to make sure I make thing easier for myself and - more importantly - easier for the people around me.

[fletchowns]

Those plans should be in place regardless of the results of a blood test

[n4r9]

I think there are many people (myself included) whose plans would change dramatically upon discovery of Alzheimer's, dementia, or some other degenerative disease. I might consider moving to somewhere with more liberal assisted suicide laws for example.

[renewiltord]

No, they shouldn’t. Makes no sense to plan for living with a mental disability if you’re not close to needing it.

I am absolutely not going to plan on a care facility right now. That sounds absolutely bogus.

[adrianN]

Notarizing any wishes against some medical procedures in case a sudden accident ruins your ability to dissent prevents doctors from being forced to keep your body alive as long as possible.

[tsimionescu]

That doesn't apply to Alzheimer's disease directly though. If you don't want to live when your conscious life is limited to short flashes of awareness among a deeply terrifying melange of visions of the past and hallucinations, DNR laws don't in any way force or even allow doctors to euthanize you. You can persist in this state for many years without ever triggering a DNR check.

[Spooky23]

My genetics are such I'm more likely to drop dead of a heart attack too young.

If I were likely to develop alzheimer's, I'd make more and more expensive accommodation for power of attorney and trusts to shield assets while I was competent to do so.

[fletchowns]

I was more referring to an advance directive / living will sort of thing

[junon]

That is one very, very tiny aspect of EOL planning.

[idiotsecant]

Yes, like walking out into the woods before it gets too bad.

[TaupeRanger]

Like what? You should already have a will, life insurance, etc. even without the disease. All you're doing by knowing earlier is causing psychological harms to yourself and the people you tell, adding more years of anxiety, grief, and sadness for no gain. Think about the bigger picture.

[lr4444lr]

Downsizing your house? Picking your long term care location? Changing your asset balance? Recording more photos, audio, and video?

Knowing an early, painful fate allows you to approach it with dignity.

[mejutoco]

That is more or less the plot of the movie "don't look up".

https://www.imdb.com/title/tt11286314/

[sandworm101]

These are 50yos, not elderly retirees. What if knowing caused your employer to deny you a promotion? Im in the military. This sort of diagnosis on one's file could have real impact on future prospects. People already fear ADHD tests for the same reason. I know a guy who is leaving the military after 20+ years flying transports. He is applying to airlines. If you were an airline, would you higher an experienced pilot with a positive alzheimer's diagnois in thier medical data?

[stvltvs]

An argument for a robust social safety net for when a diagnosis threatens your career in a safety-critical field.

[cafebeen]

While not a cure, there are many known modifiable risk factors for Alzheimer’s, so to some extent we know enough to deflect / mitigate dementia: https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

[ABCLAW]

>Refusing to improve early, probabilistic diagnosis because today’s treatments are modest confuses sequence with outcome.

While you're right from the perspective of humanity taking the steps of gathering data then tackling the disease, most developed countries have single payer healthcare systems that require some level of cost-benefit analysis to approve covering new diagnostic systems.

Alzheimer's disease progression doesn't seem to have any notable preventative indications other than 'eat well, exercise and stay mentally active', all of which are standard recommendations.

Recall that this isn't an issue deciding between funding and non-funding. It's an issue deciding between funding Alzheimer's diagnostics, new GMP agonists, new screening options for highly preventable cancers, etc. Building out a dataset is nice but unless that's surplus money redirected from other programs it's going to come at a real flesh and blood cost.

[vasco]

Alzheimer isn't new. You should compare it with a situation like:

Imagine you're born and you eventually learn that there's an asteroid on a collision course with earth, from way before you were born. It's going to take many years to get here and you may die before it hits and so far no scientists have been able to come up with a way to deflect it. Do you care?

Adding newness to the situation makes it wildly different.

[lr4444lr]

Okay but even that analogy is limited. Incurable progressive diseases almost invariably have lifestyle factors, supplements, or medications that can at least slow the rate of progression for many people. Those are also often more effective when started during early stage detection. There is literally nothing the average person can do about the asteroid.

[MadxX79]

Absolutely, the belief in scientific circles is that the way forward to develop cures (or at least treatment that slows down the progression) is to treat it early. When you get to the point where you start showing clear symptoms, your brain is already mush. If you have a potential treatment that attacks the root cause, you would have to catch the very early, pre-clinical, stages of the disease, but without good diagnostics there is no way to do that (short of giving the disease to a wide swath of the population, like a vaccine... but that gets expensive very quickly, and side effects become a bigger worry.

[mseepgood]

> We would immediately build better telescopes to track it precisely, refine its trajectory models, and begin developing propulsion systems capable of interception

That's not what would happen. We wouldn't mobilize. We'd fragment. Within days, the prediction would be declared partisan. One bloc would call it settled science; another would call it statistical hysteria. Billionaires would quietly commission private shelters while publicly funding studies questioning whether the asteroid even qualified as "large." News panels would debate whether the projected impact zone was being unfairly politicized. Conspiracy channels would insist the asteroid was fabricated to justify global governance. Others would insist the real asteroid was being hidden. Amateur analysts would flood the internet with homemade trajectory charts proving the professionals wrong. Death threats would arrive in astronomers' inboxes faster than research grants.

[n4r9]

The film "Don't Look Up" is very similar to what you describe.

[KurSix]

I get the logic, but I think the emotional side is a lot harder than the asteroid analogy makes it sound

[chaostheory]

Maybe if you can keep the results a secret from health insurance companies you’d have a point. However, not everyone has coverage under a large organization’s umbrella, and these people might be denied coverage.

[Someone]

“We have no cure. I don’t want to know.” isn’t the same as “We have no cure. We as a society don’t want to know.”

People can be fine with being tested so that epidemiologists can work on growing our knowledge and, at the same time, not wanting to know their own diagnosis.

[rossant]

I agree. I feel that many medical doctors do not share this mindset.

[_alternator_]

>”We have no cure. I don’t want to know.”

Is this a response to another comment or did I miss the quote in the article? Otherwise it’s just a straw man.

[FrustratedMonky]

When can we get it?

I do want to know.

If it is positive, that is still helping you accurately deal with whatever is happening to you.

[wordglyph]

Your gut bacteria is the prevention and the cure.

[wizzwizz4]

That's a hypothesis. If we knew that for certain, it would be really big news; and we could investigate to learn why, and then we could isolate the causative factors and perhaps find other ways of deploying them… If you know something the rest of us don't, prove it: show us the evidence, show us the specific hypotheses, describe a repeatable experiment, show us the results if such an experiment has been performed.

If you don't know something the rest of us don't, don't be so arrogant about your pet theories. Such arrogance costs lives.

[wordglyph]

You do realize they already are investigating, right? Even looking into MS and parkinson. ALZHEIMER’S DISEASE (AD) and AD DEMENTIA Umbrella review (systematic reviews of SRs): https://www.nature.com/articles/s44400-025-00048-6

Systematic review + meta-analysis (basal microbiota; AD): https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002... https://pmc.ncbi.nlm.nih.gov/articles/PMC11672027/

Replicated case-control + functional metagenomics (AD dementia): https://alz-journals.onlinelibrary.wiley.com/doi/full/10.100...

Large-cohort metagenomics (stage-specific / early pathology signals): https://pubmed.ncbi.nlm.nih.gov/40164697

Mendelian randomization (AD): https://pubmed.ncbi.nlm.nih.gov/38788075/ https://www.sciencedirect.com/science/article/pii/S227458072... https://pubmed.ncbi.nlm.nih.gov/40665707/ https://journals.sagepub.com/doi/10.1177/25424823261422629 https://www.medrxiv.org/content/10.1101/2025.08.20.25333769v...

Narrative / mechanisms (useful synthesis, not primary causal proof): https://www.sciencedirect.com/science/article/abs/pii/S15681...

MILD COGNITIVE IMPAIRMENT (MCI) / DEMENTIA (cognition-focused evidence) Systematic review (MCI or Alzheimer’s dementia; PRISMA, PROSPERO): https://www.mdpi.com/2035-8377/17/10/155 https://pubmed.ncbi.nlm.nih.gov/41149776/

Scoping review (MCI and AD gut microbiomes + interventions, through Feb 2023): https://pmc.ncbi.nlm.nih.gov/articles/PMC12825029/

Systematic review of microbiota-targeted interventions for cognition/dementia risk: https://www.sciencedirect.com/science/article/pii/S027153172...

RCT-focused systematic review/meta-analysis of probiotics for cognitive impairment risk/AD/MCI: https://pmc.ncbi.nlm.nih.gov/articles/PMC12645680/

FMT in dementia/MCI context (review of effects across neuro cohorts): https://www.sciencedirect.com/science/article/pii/S266635462...

MULTIPLE SCLEROSIS (MS) Microbiome signatures via global data integration / ML: https://pmc.ncbi.nlm.nih.gov/articles/PMC12383397/

Systematic review/meta-analysis of probiotics in MS (preclinical + clinical): https://journals.plos.org/plosone/article?id=10.1371/journal...

Systematic review + meta-analysis (antimicrobial exposure and MS risk; microbiome-disruption relevant): https://www.sciencedirect.com/science/article/abs/pii/S22110...

Mendelian randomization (gut microbiota causally linked to MS): https://pubmed.ncbi.nlm.nih.gov/39065244/ https://www.mdpi.com/2076-2607/12/7/1476

Broad MS gut dysbiosis and therapeutic modulation review: https://pmc.ncbi.nlm.nih.gov/articles/PMC12668904/

MS gut-brain-barrier and intestinal barrier review: https://www.frontiersin.org/journals/immunology/articles/10....

Example MS cohort biomarker/signature work: https://www.nature.com/articles/s41598-024-64369-x https://www.nature.com/articles/s41598-025-19998-1

PARKINSON’S DISEASE (PD) Multi-cohort metagenomic meta-analysis (Nat Commun, 2025): https://www.nature.com/articles/s41467-025-56829-3 https://pubmed.ncbi.nlm.nih.gov/40335465/

Large metagenomics cohort (Nat Commun, 2022): https://www.nature.com/articles/s41467-022-34667-x

Integrated multi-cohort gut metagenome (Movement Disorders, 2023): https://pubmed.ncbi.nlm.nih.gov/36691982/ https://movementdisorders.onlinelibrary.wiley.com/doi/10.100...

Metagenomic analysis (Movement Disorders, 2024): https://pubmed.ncbi.nlm.nih.gov/39192744/

PD causal-inference and MR discussion (review-type synthesis): https://pmc.ncbi.nlm.nih.gov/articles/PMC12512240/

MR study example (PD gut microbiota): https://journals.lww.com/md-journal/fulltext/2025/10310/caus...

[wizzwizz4]

> You do realize they already are investigating, right?

Yes. I also realise they have not reached the conclusion of this investigation. (Imagine this attitude towards a police investigation: "They're investigating Roger Rabbit, therefore he must have dunnit!")