Launch HN: Darmiyan (YC S17) – Early Detection of Alzheimer's Disease

[kvejdani]

Hi HN, I'm Padideh Kamali-Zare, co-founder and CEO at Darmiyan in the current YC batch (https://www.darmiyan.com/). We work on early detection of Alzheimer's disease.

I'm told that launching on HN should come with the backstory of how we came to work on this, so I need to tell you about my grandmother, the most precious gift in my life. She was a poet who raised me, and was always full of life and stories to keep me amazed and excited. As the first female bank executive in a conservative society in the middle east, she was also socially progressive and outstanding. A brilliant brain. A beautiful mind. A few months before she died, on a sunny day, she told me: “Do you know what I want the most from my life?” I stared at her in silence. She continued: “To die decently while I still remember myself, my memories and my loved ones. It feels like as I’m getting older, I’m somehow losing my brain. As if my brain was lemon juice before and now it’s becoming lemonade.” That statement has been stuck in my brain ever since. Her wish never came true. She died not remembering even basic things of her amazing life.

Now, 14 years later, it’s been exactly 14 years that I’m researching human brain structure and function, and modeling how they degrade with age and by diseases such as Alzheimer’s disease. Believe it or not, it has been 110 years since the initial description of this devastating disease by Dr. Alois Alzheimer. Yet there hasn’t been much progress in pre-symptomatic diagnosis of the disease and no progress in finding a cure for it despite all advances in science and technology. One in every five Medicare dollars is spent on Alzheimer’s disease and the entire health care system will go bankrupt if no revolution happens in the field. “So, what is missing?”, I always asked. And what can be done to find the missing piece? I always tried to answer. Driven by these questions, I spent several years in biological physics master’s and PhD programs and neuroscience postdoctoral research.

Now I’m the founding CEO of Darmiyan. At Darmiyan we detect Alzheimer’s disease up to 15 years before symptoms, meaning exactly when treatments are feasible and brain damage could be slowed down just by simple life style changes such as regular exercise, eating well, and sleeping well. We do this early detection non-invasively, using only standard brain MRI. We have spent the last three years in Darmiyan developing and validating a software platform that models the human brain and simulates the tissue architecture underlying every individual voxel (3D pixel) of the brain MRI. Our proprietary methodology and results have been officially reviewed and approved by clinical Alzheimer’s experts at Stanford and the world leading Alzheimer’s expert and Nobel prize winner Paul Greengard. The most challenging part of our journey so far has been to get access to the largest MRI databases for Alzheimer’s disease and clinically validate the software. Now we have analyzed more than 3000 brain scans and our software’s predictions are 90% accurate.

My co-founders are Thomas Liebmann, PhD, a top-notch experimental neuroscientist who has managed to visualize the most hidden parts of the human brain through the eyes of the most advanced microscopes; and Kaveh Vejdani, MD, an extraordinary physician who always seeks complex problems at the interface of physics, biology and medicine and solves them with high level of knowledge, creativity and innovation. Thomas was my first office-mate in Stockholm 12 years ago. We met when I had just started my PhD at the Royal Institute of Technology (KTH) in Sweden and we became friends on the first day. Kaveh and I met at a classical music event in New York 7 years ago and have been close friends ever since.

Our vision in Darmiyan is to help all those people in the world who suffer from complex brain diseases such as Alzheimer’s disease. We want them to be diagnosed early and get cured. We want to save those millions of precious brains who are unfairly stolen by Alzheimer’s disease and bring them back to their family members.

Thanks for reading to the end! We look forward to hearing your feedback and questions.

[clfougner]

"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

[manmal]

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)".

[RoboTeddy]

> 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!)

[kvejdani]

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

[brooklyntribe]

> 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.

:-)

[ScottBurson]

It's great to see people working on this problem, and I wish you the greatest success.

I'm curious what you're comparing your results against to determine their accuracy. I thought there was no way to get a confirmed diagnosis of Alzheimer's short of an autopsy. (Obviously I'm no expert -- just going by what I've read.)

[Padideh]

You are absolutely right. The definitive test to confirm Alzheimer's pathology in the brain is by autopsy, however there are pretty extensive clinical tests available that get very close to the diagnosis. The accuracy of our software is determined by testing a population of people with clinical Alzheimer's disease, against their age-matched normal controls.

[sova]

You can also have a conversation with the afflicted human being and find out. Some days are more lucid than others, but on the whole there can be a 70-90% "fog" of dementia/alzheimer's that is apparent even without a brainslice.

[manmal]

I think they are using those 3000 brain scans of people who progressed to Alzheimer's - questions arise: what part of that was the training data, what part was the test set, and did the sets overlap?

[helloworld]

This sounds awesome. How might it complement the "visual paired comparison" task of Zola et al. (2013) -- which has been commercialized by Neurotrack -- in helping to identify those at risk of dementia?

Zola, S.M., Manzanares, C.M, Clopton, P., Lah, J.J., and Levey, A.I. (2013). Am J Alzheimers Dis Other Demen. 28(2): 179–184. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670591/

[Padideh]

There are many tests to tell you the risk of developing dementia, which is only 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.

[dragonwriter]

> Now we have analyzed more than 3000 brain scans and our software’s predictions are 90% accurate.

This is really a case where the rate of false positives and negatives (and the ages of the study population) with comparison to incidence is needed, and not just a % accuracy. Just unconditionally saying “no” gives you a pretty high prediction accuracy (83% lifetime accuracy for women at 65, 91% for men at the same age, based on remaining lifetime risk of developing the disease.)

[kabowen]

Where is the mention of scientific peer-review? Where is there mention of FDA interaction? Uploading brain scans for "diagnosis" sounds an awful lot like practicing medicine to me! >> We want them to be diagnosed early and get cured This statement does not match up with the reality that there are NO validated "cures" for Alzheimer's (or any other dementia). I would stay far away from this.

[kvejdani]

There is only so much that can go into a short essay about the story and aspirations of a disruptive startup company. This story was not meant to be a scientific publication. We are working with FDA and expecting to receive approval within a year.

You can think of Darmiyan's product as a quantitative virtual microscope that, among other things, can help pharmaceutical companies come up with a disease-modifying treatment by testing the test drug on "cognitively healthy" volunteers who could potentially benefit from the drug, if it's really effective, before it's too late. Right now there is no other tool in the market to identify and monitor microscopic abnormality in cognitively healthy brains.

[nolite]

I don't think I've ever really appreciated one of these YC posts, and haven't found many of these startup missions inspiring in many years

You all, are truly inspiring and dedicating your life to making a difference. It has truly been a pleasure to read about what you're doing, and I can't wait to see how you change the world. Thank you and your team, sincerely. and all the best!

[Padideh]

Thank so much for your kind sentiments. Much appreciated. Darmiyan team is definitely committed to making a positive impact by mitigating the burden of neurodegenerative diseases on millions of families.

[gramakri]

Thanks for the touching story and it's great to see medical startups like this.

Can you clarify how you reached the 90% number given that the detection is 15 years before the disease and your startup is only 3 years old. How were these numbers measured?

If I may throw in another question, what is the biggest challenge your company faces? It looks like there is no reason not to choose your product.

[Padideh]

We got access to MRI scans from numerous people with Alzheimer's disease or MCI (mild cognitive impairment) who happened to have an MRI scan up to 15 years ago, when they were still cognitively healthy, and our software detects abnormality in those older scans with a very high accuracy.

Regarding your second question/comment, we have just launched, and you are absolutely right, there is no reason not to choose our product. The biggest challenge is the huge skepticism in the medical community towards any novel technology related to Alzheimer's disease, given all prior failed big claims by others.

[Koshkin]

What does early detection of Alzheimer's give you, given that it's untreatable? And, isn't ignorance bliss in this case (i.e. the less time you spend knowing about the problem, the better)?

[pfarnsworth]

I agree. After seeing how my mother has been ravaged by dementia, I would prefer to not know 15 years in advance. She was in relatively good health and exercised, etc, and took medication to help slow down the disease but it didn't help. I would rather just not know and commit suicide once I am in the moderate stage of dementia. It really is that bad.

That combined with the relatively high false positives makes this a pretty bad investment so far, in my opinion.

[Padideh]

Lifestyle changes such as regular exercise, better sleep and better nutrition are shown to reduce the risk of developing Alzheimer's dementia later in life. Also, when a disease-modifying treatment is found, the person who knows the status of their brain health will be the one to benefit most from the treatment before developing symptoms. Once symptoms of cognitive decline show up, it may be too late to intervene.

[alakin]

There are a really large number of companies working on eliminating up stream causes of Alzheimer's, many with promising results. So early detection gives you time to find out if there is something you can do about it, to prepare for the eventuality, and to save a bit of money for treatment.

[sova]

Hello and thanks for your excellent and noble endeavor in healing the world of Alzheimer's.

What is the current state-of-the-art in treatment (2017, Aug)? As an interested person, I have recently heard on Radiolab that MIT has done research with using 40Hz light to trigger brain-cleansing circuits that pulsate through the plaque buildups. Is this the most promising form of treatment at this time?

Another question I have had for a long time but have had no strong-science-strong-medicine-strong-research friends to ask in this domain is: What is the plaque? What causes it, how do we uncause it / remove the root of it, and is it a natural part of the brain chemistry out of balance, or a foreign invader?

Thanks a lot, hope these questions are within what you are able to talk about at this time. Wishing you the best of luck and success in your endeavors, and I look forward to living in an Alzheimer's-free world one day!

[DanBC]

You might be interested in "Beyond Amyloid": https://www.statnews.com/2017/08/18/beyond-amyloid-alzheimer...

[cicero19]

What types of sequences does your algorithm run on (looks like DWI/ADC)? One could make the argument that if it is on standard sequences done for other diagnostic purposes, hence not requiring any additional time or money, this tool could be used to provide info to radiologists who are not typically going to look for these changes (nor can they do this as precise as machines).

I am working in a similar domain (www.16bit.ai) and am a radiologist. I think there is utility in this quantitative analysis despite there not being an intervention yet, despite what others are saying. The reason is because in order for others to measure the effectiveness of new treatments a gold standard and reproducible way of measuring the disease is necessary. I think drug companies working in this area would be quite excited about this if it can be shown to be a reliable predictor. As for direct to consumer marketing (ie. 23andme model) that some have suggested - its possible but it will be tough to educate patients to go and get their MRI images from their hospital for this purpose. I live and practice in Canada so my views and experiences of this may be a bit skewed. Best of luck!

[zitterbewegung]

Can you give a reference or paper of the exact lifestyle changes you need to perform to reduce the risk of Alzheimer's?

[helloworld]

Here's one approach that seems to have achieved some success:

A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial

http://www.thelancet.com/journals/lancet/article/PIIS0140-67...

[jmcgough]

How helpful is early detection when there's no effective treatment yet?

[Padideh]

There is no cure because there is no "early detection". By the time of current clinical diagnosis (when symptoms appear), the disease has progressed to advanced stages and it's too late for any effective treatment. Our goal is to help pharma companies develop novel drug candidates that can potentially cure the disease "if detected early using our technology". Also, life style modifications are known to delay the symptoms. So knowing is always the best.

[djohnston]

I think the general consensus is that by the time you're 75 and symptomatic things have already been going downhill for decades and it's unlikely that much can be done to stop or halt the disease. Thus, while there are no proven treatments at the moment, the candidates more likely to succeed are those that attack the disease process early. In that light, early detection is extremely helpful.

[jsniff]

aren't these stats horrible?

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?

[subroutine]

Prevalence is over 40% if you live into your 80s.

[swsieber]

What do you mean by 90% accurate? Do you mean for every 1/10 people analyzed, a result is wrong? That would be a lot of false positives.

[kvejdani]

Somewhat correct. If you test the software with a 1000 MRI scans from people with known diagnoses, the software will diagnose ~900 of them correctly. Roughly 97% sensitivity (3% false negative) and 85% specificity (15% false positive). False positive here is not real false positive, as the software is detecting abnormality in people who are still cognitively normal.

[got2surf]

1/10 false positives doesn't sound too bad to me. Having seen older family members impacted by the disease with little to no warning, a 90% chance at early detection would be incredible. Even with a false positive, the changes you would make (lifestyle changes, brain stimulation, continuous monitoring) would only be beneficial, IMO.

[redlollipop]

Interesting post! Curious about two statements made in your post:

"Our proprietary methodology and results have been officially reviewed and approved by clinical Alzheimer’s experts at Stanford..."

What is an "official review and approval" process?

"The most challenging part of our journey so far has been to get access to the largest MRI databases for Alzheimer’s disease..."

Which dataset is this?

[lquist]

Is this product in development right now? How can I submit my brain MRI for analysis by your company/software?

[kvejdani]

Great question. Web upload tool is in development, will launch in a few months. Stay tuned!

[sova]

HappyCat pocket CatScan! It's coming, just wait.

[anilgulecha]

Hi, when you say 90% accurate, that basically means you're able to detect 9/10 potential cases, and could save a lot of money for insurers/health providers. This is an incredible number!

What was the state of the alzheimer-detection-world prior to this?

[kvejdani]

There is currently no other early-detection technology to show (and measure) microstructural abnormality in the brain before symptoms of cognitive decline. State of art Amyloid PET is extremely non-specific, with a positive predictive value of 50% (coin toss).

[aamody]

Love the story and what you'll are working on, good luck!

[Padideh]

Thanks a lot!