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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.

[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.

Can you provide the source for the 95% figure?

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...

> 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.

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

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

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.

> 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.

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?

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.

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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.

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)

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.

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?"

>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.

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

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

In the US or in countries with working healthcare?

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?

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.

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?

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.