A blood test accurately diagnosed Alzheimer's 90% of the time, study finds | Hacker News Reader

A blood test accurately diagnosed Alzheimer's 90% of the time, study finds

nytimes.com

46 pointsm46321 comments

This is fantastic and a great step in the right direction, especially with the new treatments (mentioned in the article also). Unfortunately we still have doctors that either do not care enough or are not skilled enough to order simple blood tests.

Me, my wife, and my father all have various auto-immune issues. It's been a frustrating fight on all three fronts to get any sort of testing done. For myself this has spanned over a decade now. My dad's journey is just starting, but we've had to switch specialists numerous times to get one that would actually DO something.

For my wife, we begged two previous PCPs for years to get an ANA and rheumatoid factor panel done because I suspected she had rheumatoid arthritis. Those tests are simple and more importantly, they're cheap. No reason to not do them in the context of patient's complaints about chronic pain, especially if they provide peace of mind and rule out serious causes. PCPs consistently brushed it off as anxiety and stress. We finally found a new PCP to take it seriously, so lo and behold: positive blood tests for both ANA and Rheumatoid Factor!

It's absurd that we have all these tools available to us, but they're not being utilized in many valid cases where they'd be useful. So while the article mentions this would be a way to start treatment early by detecting the disease earlier, I have low confidence in the health system to take that initial step.

For context Rheumatoid Factor is present in 4% of the healthy population, an even upto 30% in certain populations like native Americans [1]

ANA is positive in 15% of the population [2]

The idea that the tests rule out serious causes is not really correct, people can have seronegative inflammatory arthritis in which case these tests are negative. Peace of mind is dubious as well given that even with a positive test you are still more likely to not have an inflammatory arthritis.

It’s a common misconception that blood tests are binary and provide concrete answers. Sometimes they do. But most blood tests, like many measurements, are far from binary and have a distribution across the normal population, once it passes an arbitrary threshold it does not necessarily mean you have disease X, context (clinical history and examination) are often far more important in making a diagnosis.

Unfortunately some of the population tend to overweight blood tests vs a physicians assessment, I guess they see the former as an objective measure and the latter as subjective. Especially because if you shop around enough clinicians you’ll eventually find one who will say what you want to hear and that one will inevitably be ‘right’.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3845430/ 2. https://rheumatology.org/patients/antinuclear-antibodies-ana...

Thanks for the information. I've been diagnosed with seronegative inflammatory arthritis myself, so I understand that the blood tests are not perfect; and "rule out" was used loosely to mean "unlikely to have". All of which is not really relevant to my point. My point was that health practitioners have become too comfortable with using anxiety (without evidence) to brush off patient concerns instead of utilizing cheap diagnostic tests to aide in the exploratory process of diagnosing a patient accurately.

In the case of my wife, once both blood tests came back positive, she was properly referred to a rheumatologist to continue monitoring her symptoms and their progression. That is how the healthcare system is supposed to work. Run tests, if it comes back positive, keep investigating with the right specialists that are more experienced in the area, then continue to look for signals that a diagnosis is accurate. Not this hand-wavy speculation with lack of evidence we experienced early on. Now that she has started to develop rheumatoid nodules, it's becoming more accepted by her healthcare team that this is rheumatoid arthritis.

Study: https://jamanetwork.com/journals/jama/fullarticle/2821669

Gift link: https://www.nytimes.com/2024/07/28/health/alzheimers-blood-t... (courtesy u/bookofjoe)

https://news.ycombinator.com/item?id=41117254

https://news.ycombinator.com/item?id=41099517

https://news.ycombinator.com/item?id=41094443

https://www.cnn.com/2024/07/28/health/alzheimer-blood-test-p...

https://news.ycombinator.com/item?id=41094571

To summarize the paper more technically:

In a large cohort of patients with cognitive decline symptoms, it predicted with 90% accuracy which patients are determined by specialists to have Alzheimer's.

This is in contrast to a 60% correct diagnosis rate by general practitioners.

The test has both 90%+ specificity and sensitivity.

The proposal is that this could improve the overall diagnostic rate by GPs by giving them a blood test to use when they are suspicious of Alzheimer's.

"The test has both 90%+ specificity and sensitivity." This by itself feels like a big deal, even if we strip away the Alzheimer's context. Do we have a lot of blood tests that are both sensitive and specific to this degree?

Seems important as a clinical substitute/adjunct for existing diagnostics (especially because they suck for other reasons), but the base rate for Alzheimers is just 10%, so like, you couldn't really run this on a whim, right?

I mean, part of the reason why I ask this question is that specificity and sensitivity tend to be inversely related: as a test becomes more sensitive, it tends to become less specific, say.

(While I'm here, in case folks are lacking the statistics background: specificity and sensitivity refer to the probabilities that a test will return with a negative test result in the absence of a condition or a positive test result in the presence of a condition respectively.)

Most of the "promising" tests I've seen tend to be something like 80% sensitive and 20% specific (testing for Lyme disease comes to mind), which makes them no better than flipping a weighted coin. The fact that this Alzheimer's test beats that feels like a big deal on the probability merits alone, and I can't think of basically any other tests that do that. (Serum cardiac troponins maybe?)

They don't offer any tests for "general population" situations, only "people we think might already have dementia". This is a really strong filter up-front.

I suspect the test would be high sensitivity very low specificity in the general population, but that is an intuition not backed by any data.

Aha, yeah, restricting your population could certainly have that effect on the specificity.

Thanks for clarifying.

For what it's worth, I'm not sure specificity/sensitivity is the limiting factor here (for doing broad population surveys with this test); it's the low base rate of Alzheimers relative to the specificity. At 90% true positive and 10% base rate, I think? (I suck at math) a positive test has like a coin flip chance of being right?

We're in the realm of probability, which is mysterious sometimes even to people who have a math background. I didn't fully grok it until I studied intensely for my first actuarial exams. (:

This kind of thing is almost always a weighted coin toss: with sensitivity or specificity alone, you only have two possible outcomes (present/relevant, absent/irrelevant), and the thing that changes is the probability distribution of those outcomes.

Combining the two gets you the full four: present and relevant; present and irrelevant; absent and relevant; and absent and irrelevant. Taking the uniform distribution, they're all 25% likely, but the idea is to find a probability distribution that makes the "present and relevant" and "absent and relevant" outcomes more likely.

Since I myself don't work in a clinical setting, I simply hadn't considered that the clinician would want to exercise discretion in pre-screening for specificity before ordering the test in order to get there. Oops.

I'm just saying, 90% true positive rate, 10% base rate, 1000 pts:

* 100 true positives

* 100 false positives (100-90=10% of 1000)

That's still just a 10% false positive rate across the population, but if you get a positive test, it's only 50/50 correct.

Did I do this wrong? I'm assuming I did this wrong.

I think you may be close but likely for the wrong reasons. I had to sit down with this for a moment to feel comfortable with it.

If we take your 10% base rate to be disease prevalence, that gives us 100 sick and 900 well.

Of the 100 sick, something with 90% sensitivity should get me 90 true positive tests and 10 false negative tests.

Of the 900 well, I should expect to see for a test with 90% specificity, what, 80 false positives and 810 true negatives? if I did my arithmetic right?

> you couldn't really run this on a whim, right?

yes, it is meant for the context of "a doctor thinks this patient may have Alzheimer's". They don't even test it in a "general population" situation.

Its not presented as a screening test.

There is a dead comment which is actually quite interesting:

> The specter of dementia frequently makes me want to not live all that long.

What’s the point of knowing you’re probability of Alzheimers if there is no cure or means to delay it. Its just a shadow constantly looming over you and can be used in the future to deny you opportunities.

We already know of many factors that delay Alzheimer's, there are likely new ones to be found as well.

Aplogies, i know very little about the subject. I just went by the article:

> Testing recommendations could change if scientists find drugs that can delay or halt Alzheimer’s pathology in people who have not yet developed cognitive problems. But for now, said Dr. Boxer, “most of us feel like it would not be ethical to use it in people who don’t yet have symptoms, unless it’s in the context of a research study.”

[dupe]

Some more discussion: https://news.ycombinator.com/item?id=41094571

https://archive.is/Hduyw

The specter of dementia frequently makes me want to not live all that long.

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