Comment by clfougner | Hacker News Reader

Comment by clfougner | Hacker News Reader

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"At Darmiyan we detect Alzheimer’s disease up to 15 years before symptoms" (original post)

"At present, there is no definitive evidence to support that any particular measure is effective in preventing AD"[1].

"Now we have analyzed more than 3000 brain scans and our software’s predictions are 90% accurate." (original post)

"In the United States, Alzheimer prevalence was estimated to be 1.6% in 2000 both overall and in the 65–74 age group"[2]

I'm assuming the 3000 brain scans you're referring to is from individuals which progressed to Alzheimers, or at least a dataset with such individuals highly represented (if this were 3000 random individuals, at a 1.6% prevalence, that amounts to 48 individuals who eventually got Alzheimers).

So according to my calculation of Bayesian probability, with a 90% sensitivity (as I'm interpreting your comment), and a 1.6% prevalence in the population, a randomly screened individual with a positive test will only actually have a 12.8% chance of getting Alzheimers. So you'll be diagnosing lots of people so that they can have an impending Alzheimer's diagnosis hanging over their head for the remainder of their life without actually being able to do anything about it, and of this cohort just over 1 in 10 people will actually end up getting Alzheimers.

Please tell me you're only planning on offering this for researchers, and not actually going to try to get individuals screened? Or am i missing something about your value proposition?

    [1]https://en.wikipedia.org/wiki/Alzheimer%27s_disease#Prevention
    [2]https://en.wikipedia.org/wiki/Alzheimer%27s_disease#Epidemiology

Edit: fixed sensitivity vs. specificity error

They could market it as an exclusion test - "Congrats, you will not have Alzheimer's in the next 15 years" vs "Sorry, we can't say for sure that you don't have Alzheimer's. Why not upload your 23andme data here, and we combine your high risk alleles with our confidence of you having the disease, to produce a higher confidence result. Also, here is a list of lifestyle changes that reduce your risk of Alzheimer's (and also stroke, heart attack etc)".

We understand the level of rightful skepticism from the community given all previous failed big claims by others. There are many tests to tell you the risk of developing dementia, which is merely a "probability" number. Darmiyan's brain maps show (and measure) the actual pathology (neurodegeneration) in the brain, at microscopic resolution.

There is currently no other method to detect and quantify micro-structural abnormality in the brain at presymptomatic stages of dementia, which is one of the main reasons why all clinical trials of Alzheimer's test drugs keep failing one after another.

When a disease-modifying treatment is found using our technology (and practically impossible without it), the person who knows the status of their brain health will be the one to benefit most from the treatment before developing symptoms.

Why do you think a lack of ability to detect/quantify these micro-structural abnormalities is hindering clinical trials? Is it a problem of detection lag?

How will your tech enable a disease-modifying treatment? Is the hypothesis your tech is the first way we can even measure?

Are you using standard MRIs and just a layer of software, or do you require some sort of special physical device?

This is all curiosity btw; I love the idea. I used to work on software for confocal microscopy and protein melting curves (to be clear, two different labs) before selling out and working on ads.

> a randomly screened individual with a positive test will only actually have a 12.8% chance of getting Alzheimers

Darmiyan folks, is this correct? If so, what are the implications for the utility of the test?

(No matter the answer it feels like this research is important -- thank you!)

Darmyian founders wrote the following in another post[1]:

> Roughly 97% sensitivity (3% false negative) and 85% specificity (15% false positive)

So with this information, the calcuation of Bayesian probability is as follows:

    (0.97*0.016)/(0.97*0.016+0.15*0.984) = 0.095

So a 9.5% chance of actually getting Alzheimers within the following 15 years if Darmiyan's test is positive. I don't have much formal statistical training, so I'm all ears if I'm making a mistake in the calculation here.

They also write the following:

> False positive here is not real false positive, as the software is detecting abnormality in people who are still cognitively normal.

Which is a terrible excuse - abnormality is only clinically relevant if it leads to disease. By this logic I can create the world's greatest test for cancer simply by saying that every given individual has cancer (100% sensitivity), and if they don't have it yet, they do carry the genetic abnormalities that will lead to cancer eventually - no "real false positives", right? Simply saying that "sooner or later, our test will prove correct" is not good enough here.

Founders of Darmyian: I commend your efforts in this space as a tool for research, and can potentially be very valuable for clinical trials. However, offering it to consumers as a screening tool when there are no proven preventative measures is - in my opinion - completely unethical and comes across as an attempt at trying to profit off fear mongering.

    [1] https://news.ycombinator.com/item?id=15083617

Darmiyan's product is NOT a probabilistic risk assessment test, and is NOT intended for use by the general public. There are already too many tests in the market for risk assessment, which are just probability numbers. Darmiyan's product is a software for quantitative assessment of micro-structural abnormality (neurodegeneration) in every voxel of brain MRI. You can think of it as a quantitative virtual microscope. Our maps and reports are not intended for use by the general public. Once we receive FDA approval in about a year or so, the Darmiyan test (software analysis of brain MRI) has to be ordered by a physician and interpreted by a physician to assist in clinical diagnosis and intervention recommendations, if any. The guidelines on Darmiyan test indications and interpretations will be determined by the medical community.

I used an online Bayesian calculator, and can confirm that the math checks out

There's currently no method to screen brain tissue health at the microscopic level. Darmiyan aims to provide that tool.

> 1 in 10 people will actually end up getting Alzheimer's.?

I have never seen anyone over 75 that does not have some kind of dementia. Zero. Alzheimers and Dementia will soon be one of the same classification. It's happening.

Nature is just telling us, you have to go. It will be incurable, it's painless. She's being nice to us. Yes treat it, of course, but we have to let go sometimes.

PS, I work with seniors. People have NO CLUE to what these people go through. Zero.

And NO one can face this question, eventually, we die. Know the millennials don't believe that. They can't even comprehend it death. But it's true. Really. And it's OK.

So live life as it should be. For ALL our days are numbered. Don't worry, be happy.

:-)

I am assuming you're making a larger point about life and death, and on that level I agree with you. But as someone who also works with seniors full-time, I have to point out that Alzheimer's is:

- not the same as dementia, and never will be [1]. Dementia is an umbrella term that includes many diseases (e.g.: Parkinson's, etc), whereas Alzheimer's is just one of the many specific diseases with its own causes, symptoms, and chances of developing a cure.

- not painless. Apart from increased physical pain sensitivity [2], there's endless emotional pain that impacts the patient and their loved ones [3].

The point you're making about the inevitability of death is valid, but it shouldn't lead to the conclusion that we should just accept Alzheimer's as an incurable disease - of all the ways that a loved one can pass away, many families I work with would agree that this may be one of the worst.

Having worked with thousands of end-of-life clients, I am surprised that the research funding for Alzheimer's is far lower than that for cancer, heart disease, and HIV/Aids. My assumption is that people's view of Alzheimer's is rooted in the old and incorrect perception that it's an inevitable and natural part of aging, sometimes referred to as "senility."

Today we know a lot more about Alzheimer's, and I would challenge anyone to point out why Alzheimer's is fundamentally incurable - it's just a matter of when, and I certainly hope we'll find a cure sooner than later.

[1] https://www.kindlycare.com/dementia-vs-alzheimers/ [2] http://www.psychiatryadvisor.com/neurocognitive-disorders/al... [3] https://www.kindlycare.com/still-alice-portrait-of-a-disease... [4] http://www.aarp.org/health/brain-health/info-2015/alzheimers...

You should disclose that you work for kindly care if you are going to link them as a resource to your argumentations IMHO...

Sorry but you are ignorant if you think that dementia is painless. My mother has dementia, and it's a horrible, horrible disease. She is going to a tremendous amount of pain, because she is confused and scared and angry. She knows something is terribly wrong all the time, but she doesn't know. She has written notes to herself that she wants to die. She can't control her bodily functions anymore and has to endure the humiliation of being bathed by strangers that scare her. It's a horrible horrible disease, and it is not painless or peaceful. I wish she would get cancer so that she could die quicker, that's how terrible this disease is.

While it is true that many of us will experience some kind of brain failure (if we don't die of something else first) making claims about absolutes like "zero" and "none" are not perhaps constructive to the conversation. My experience with my 90-year-old father in law is that he can recite far more stories about being 10 in rural Kansas in the '30s than I can of being 10 in Colorado's suburbs. He'll also demolish any who care to challenge him at Scrabble or contract bridge. Also, he happens to be the nicest, most unassuming guy ever. Dementia may eventually come for him, but today is not that day. YMMV

Using anecdotal evidence and giving empty platitudes isn't really scientific nor does it make people feel better. I am a millennial that believes that I can die. I also think that diseases like Alzhemiers are the result of increasing our life expectancy. But, since we have pushed our life expectancy higher now our task would be to improve our quality of life.

> I have never seen anyone over 75 that does not have some kind of dementia.

> PS, I work with seniors.

My fiancee says something similar, but she's a resident in a hospital, so she tends to tag "... in the hospital" or "... in the ICU" on the end of that statement because she's not seeing a random sample of all >75-year-olds.

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