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.
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.)
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.
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.
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.
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)
> 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.
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.
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.
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.
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.
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.
> 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.
“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.
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.
PSA to those with family affected by dementia/Alzheimer's at a relatively early age (say <70yo): Get them tested for STDs, specifically Syphilis.
Left untreated for a very long time (decade+), it spreads to the brain and causes dementia among other things. Older generations with stigmas, taboos, or from lower educational backgrounds seem (to me) less likely to get tested, so it seems plausible.
Source: Have recently discovered this myself with a family member from their neurologist.
> Source: Have recently discovered this myself with a family member from their neurologist.
The reason this was detected is that such testing is a standard practice with new dementia patients—among many other tests that identify etiologies of dementia.
For a disease which (to my knowledge) can’t be slowed down or reversed, I think it’s a fair question why we would want to detect Alzheimer’s. Maybe there are other reasons, but my suspicion is that we will be able to, and an easy detection method significantly widens the pool of subjects to study later on.
If it turns out that driving a Prius on Tuesdays slows down Alzheimer’s, a larger pool of subjects would allow us to figure that out.
I would personally want to know as early as possible, so I could get my affairs in order and register my wishes around end of life care and euthanasia while I am still recognised as having full mental capacity.
It's also better for people around the Alzheimer's patient, as it will let them understand why someone's personality and behaviours may be changing, and possibly let them be bit more forgiving of such changes. It will also give family more time to plan and understand the health and community services and support are offered wherever they live.
I know two people who have been taking the new monoclonal antibody treatment for it. One who was a bit further along when she started, and did not show any significant improvement. The one who started while she was still in the early stages has completely arrested her descent. She hasn't recovered much of what she already lost, but she's still able to live independently and enjoy life, and her mental acuity scores are (slightly) better than they were last year. That's a hell of a thing.
I also know someone who's significantly better now than they were a few years ago thanks to alzheimer's medication. And Trontinemab, which is currently in phase III trials I believe, seems even better than what is publicly available as it crosses the blood-brain barrier more readily. We're entering a brighter future for alzheimer's patients.
Completely arrested? I don't. But it appears to be arrested in ways that matter for mental acuity, for now. I've taken care of a parent with Alzheimer's, and helped several other caregivers over the years with their own family's journeys, and one thing I can tell you is that I have never, ever seen an actual halting of the progression for this long. The descent is usually a stairstep pattern, but the steps are on the matter of weeks to a month or two. My friend has been stable for a year.
This is all new. There is research hinting at Alzheimer's subtypes, some of which are more likely to respond than others. Even halting the decline is a huge potential breakthrough.
The way I’ve watched Alzheimer’s work in a family member is that it’s a step down function rather than gradual. And once something is lost, it doesn’t come back. So anything that can delay the next step even just for months is a win right now.
That's 4–6 months in the 18 months the trials lasted for, i.e. about a 30% slowdown of progression. The open-label extensions suggest this relative slowdown seems to continue at least to the 4-year mark (at which point it would have bought you over a year of time): https://www.alzforum.org/news/conference-coverage/signs-last...
Time will tell if the 30% slowdown continues beyond four years, and/or if earlier treatment with more effective amyloid clearance from newer drugs has greater effects. The science suggests it should.
It's very useful to understand what you're struggling from even if it's not curable. It explains your symptoms, your experience and help you understand what you're going through. Understanding that you're suffering from something incurable is also helpful in not looking for other ineffective methods to cure a mysterious illness.
Most people get a dementia (or related) diagnosis after they are deep enough in it so that they cant do much about it or get their affairs in order.
My grandfather had a "fall" at work, he then left that job, and held down 2 more engineering jobs before he was diagnosed with a stroking condition and subsequent dementia. I got the distinct impression he thought he had more time, but rapidly declined.
If he knew he was short of time before his rapid decline he probably would have done things differently. Like not buying a house he would later have to sell to pay for aged care.
If he knew he was at risk of a workplace accident he probably wouldn't have worked as an after hours safety engineer at a major treatment plant, where if the worst had happened he could have endangered others.
At a personal level, I've been through this with my grandfather.
I want to know. My family wants to know. I want to prepare because there are things I want to do today that I know I won't be able to do in the future.
In many ways, it's just like many terminal cancer diagnoses. You're going to lose that person, but you have some time.
But it is a wildly variated, almost meaningless diagnosis. 3 of my 4 grandparents got Alzheimer's diagnosis as well as my mom and mother-in-law. The variation of progression and symptoms is so wide that it really seems like a catch-all. One grandmother was fine until about 72 and in 2 years forgot who people were and 4 years had lost all executive function and passed away. The other one was diagnosed in her early 80s and lived to be 96 with no major progression, like slightly more repeating, but never forgetting people or not knowing how to talk etc. Similar dichotomy between my mother and mother-in-law but with considerably different presentations of symptoms.
It's a weird disease and IMO not even really a disease it's a bunch of different causes of cognitive impairment under one umbrella but shouldn't be separated out much further to find actual causes and treatments.
The accuracy of this test is nowhere nearly good enough to do population-wide screening. The clinical setting for this test is memory clinics in which Alzheimers is already relatively highly likely differentially, and even there you're going to get a surprising number of false positives.
(There's enough info in the supplemental link on this page to have an LLM do the Bayes math for you.)
> doctors correctly diagnosed Alzheimer's in 75.5% of cases, but when incorporating blood test results, diagnostic accuracy increased to 94.5%
These patients are already seeing doctors. Would you rather your doctor to hide the diagnosis just because your disease isn't curable (for now)? It's not like we're testing the whole population in masse.
Being able to know someone's risk factor would be important for how we treat elderly people. I know someone who is 85 and super sharp (previously worked as a corporate accountant and banker), they still have a better memory than a lot of 40-50 year olds, and yet they are constantly harassed by eldercare "agents" for the state because whenever they make a investment decision that is even slightly questionable they get reported to the state by the bank. Sometimes the bank refuses to authorize transactions. If they could conclusively prove they aren't at risk I think they would be left alone much more often.
If the patient still has periods of lucidity but the disease is suspected to be advancing, knowing they have it could prompt them to get their legal affairs in order.
I assume this is hugely beneficial for research on intervention methods, not for treatment. I think everyone is focusing on "I'd rather know" but imagine if you could get larger populations with a diagnosis earlier on, how impactful that would be for testing an intervention?
Not saying anything about the article at-hand, but assuming we were able to detect it with such certainty, I think it would greatly increase the funding, rigor, and breadth or research devoted to finding a cure or treatment that actually worked.
Having struggled with hard to diagnose health issues before, I can’t emphasize enough how much of a relief it is to put a name on the disease that is causing you so much harm.
It is frankly shocking to think disease diagnosis would be a useless thing
For 20-ish% of Alzheimer's patients, the Shingles vaccine may be a treatment. This has been suspected for a few years now but has received recent confirmation studies.
While the study was about the shingles vaccine, I wonder if having passed normally through shingles influences positively or negatively the chances of later developing Alzheimer's.
Trontinemab is in trials right now and has 92% of patients achieving low amyloid levels. And more people should be able to take it as it causes less brain swelling (ARIA-E). I'm unaffiliated, I just follow medical research in my free time. But I'm quite hopeful about this medication
Nobody is ever going to do that with this test, because the overwhelming majority of positive test results in a population-wide sample will be false, and the proposed diagnosis is devastating. This is a test for people who already have symptomatic dementia that helps confirm the diagnosis.
Well this test isn't for whether you will get Alzheimer's, so that disqualifies it before we even consider the accuracy.
But apparently your odds go above 30% if you live long enough, so if you could test for being in that cohort I think that result would be too common to actually be devastating.
> Tell 50 million people they’re likely to have Alzheimer’s then tell them where to donate towards a cure, or treatments to slow it by a decade.
Pharmaceutical companies have spent something like $50 billion on developing Alzheimer's drugs with, well, the most furtive of straw-grasping to show for it. It's probably the most expensive single disease target (especially as things like cancer are families of diseases)... the failure to have good results isn't for lack of money, and merely throwing more money at it is unlikely to actually make progress towards meaningful treatments.
It just seems really obvious to me that it's not one disease. One problem with the research is that there is SO much money. It's corrupting. There's a whole thing about the plaque cartel and if you aren't testing around a possibly flawed concept the availability of funds is much lower.
I just feel the thinking is off, it's like we are trying to treat cuts by removing scabs and scar tissue. We really need deep investigation on the sources, which I feel in many cases are industrial chemicals and how some people's body / immune system respond to them.
One of the most compelling studies I saw was how distance from a Golf Course predicted neurodegenerative diseases, based on their use of certain pesticides.
I understand the "detect deadly progression but no cure" problem; this was the same rationale people used when Huntington disease could be verified in diagnostics. Many people don't want to know, but some want to know, in particular as you can manage some things here or there - diet affects many things, for instance, even aside from metaboic genetic defects. And for any (molecular) therapy at a later time you need to understand the molecular basis to some extent. Some things can be found out via trial and error (vaccination and before) but for some disease that can not work. Alzheimer is quite complex.
If a loved one is suffering from this, this diagnostic would allow for interventions such as guardianship to assume financial and logistical responsibility for them with less subjective decisioning based on observations alone.
Even though it cannot be reversed or eradicated (yet, let's hope) detection can allow individuals to adopt interventions that help either adjust their lives to better cope with its progression or help mitigate some of the detrimental behavioral consequences. In addition, if you have family to care for it may be impetus to get certain things in order for them before later stages of the disease, etc. It's horrible and bleak, but I could certainly see why one might want to know.
In the lucky case, it can also relieve anxiety. Even though false negatives may still be possible, receiving a negative detection might give people who have anxiety about certain symptoms relief, since they can rule out (rightly or wrongly) a pretty severe disease.
that doesn't bother me but what is actually suspicious is persistently only mentioning "accuracy" but not sensitivity / specificity / precision etc.
Basically, almost everybody doesn't have Alzheimers. Sampling from the general population you can get better than 94.5% accuracy just by returning negative on every test. You have to know sensitivity and specificity separately to make any informed judgement ... which they try extremely hard not to tell you.
> Compared with the final diagnosis, the pre-biomarker diagnosis was maintained in 71/200 cases (75.5%) (Kappa = 0.576), while the post-biomarker diagnosis was maintained in 189/200 cases (94.5%) (Kappa = 0.906).
Even without this method, the doctors have been able to give diagnosis with 75.5% accuracy (according to the paper's claim).
I.e. it needs the original 75% accuracy or so and boosts it another 20%.
The problem is that the assessment itself is slow, expensive and requires skill.
What we really want from a test is high specificity (a positive test means you have accuracy) and high sensitivity (if you get a negative test you don't have it).
Maybe I've misunderstood something, but how can they know the accuracy of the test? It is the best test out there, so if it misses a diagnosis, how do they reliably catch the false negative?
Besides being a bad joke, this is in terrible taste on a thread read by people with Alzheimer's patients in their lives, and it violates HN's rules that discussion should be valuable and inspire curiosity.
One of interesting checks in this study might be to check when (if) any of the participants had taken this vax and what the impact might be on an Alzimer's diagnosis.
Purely anecdotal, but I witnessed a person starting to experience a severe cognitive decline right after the two doses of the Shingles Vaccine. It can surely be a coincidence, but I was very surprised when I read about this study.
This needs to include life-changing false positive rates. Imagine being given a diagnosis like this - people around you who know and any corporations who can sniff it out by snooping on your communications can lead to much rejection early in life. What happens when the diagnosis is as positive when it shouldn’t have been?
https://doi.org/10.1038/s41591-025-03622-w this is the paper they're basing the research on. So in primary care, the accuracy rates are in the 80s. So that's something like a 17% false positive rate. That's still like 5 to 1 odds of getting a correct result though. It's much better than nothing.
I got bad news about the specificity for most things this serious. Think the only one we absolutely nail is infectious disease detection.
Spoilers: It's anywhere between 1-15 and 5-30% for false positives and 1-15/5-40 for false negatives. That's imaging, biomarkers, cancer screenings, etc
Like, where do you think the concept of "second opinions" came from? Whimsy? Lets go ask a second doctor if I actually have cancer, it'll be fun!
This statement is quite broad and misses several important factors.
First of all, a test's sensitivity and specificity. The math in your example assumes a balanced test, but on what basis? The math comes out quite different for high-sensitivity or high-specificity tests. (Unfortunately, I could not find the numbers for the test in the linked article.)
Secondly, whom are we testing? The prevalence rate in your example (1%) is unrealistically low even for the general population. But would we screen the general population? No, we'd screen high-risk groups: the elderly, those with certain APOE genotypes etc. Predictive values of a test depend hugely on the prevalence rate.
Lastly, it depends on how the results are used. If it's a high-sensitivity test used to decide whom to send to the next tier in a multi-tier diagnostic system, it could actually be quite effective at that (very rarely missing the disease while greatly reducing the need for more expensive or more invasive testing).
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.
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