
Launch HN: Darmiyan (YC S17) – Early Detection of Alzheimer's Disease - kvejdani
Hi HN, I&#x27;m Padideh Kamali-Zare, co-founder and CEO at Darmiyan in the current YC batch (<a href="https:&#x2F;&#x2F;www.darmiyan.com&#x2F;" rel="nofollow">https:&#x2F;&#x2F;www.darmiyan.com&#x2F;</a>). We work on early detection of Alzheimer&#x27;s disease.<p>I&#x27;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.<p>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.<p>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.<p>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.<p>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.<p>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

~~~
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.

:-)

~~~
aerosmile
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/](https://www.kindlycare.com/dementia-vs-alzheimers/) [2]
[http://www.psychiatryadvisor.com/neurocognitive-
disorders/al...](http://www.psychiatryadvisor.com/neurocognitive-
disorders/alzheimers-patients-more-sensitive-to-pain/article/417651/) [3]
[https://www.kindlycare.com/still-alice-portrait-of-a-
disease...](https://www.kindlycare.com/still-alice-portrait-of-a-disease/) [4]
[http://www.aarp.org/health/brain-
health/info-2015/alzheimers...](http://www.aarp.org/health/brain-
health/info-2015/alzheimers-research.html)

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

------
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.)

~~~
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.

~~~
hprotagonist
In general, you can't discriminate between dementia and alzheimers with a
patient interview.

~~~
Padideh
Correct. Alzheimer's disease is the most common cause of dementia (~80%).
There are other dementia's such as FTD (frontotemporal dementia), DLB
(dementia with Lewy body), vascular dementia, etc.

------
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/](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)?

~~~
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.

~~~
manmal
Sure, but why not defer the test until a viable treatment is invented?

~~~
Beltiras
You might need to know about progression in the early stages to come up with a
treatment plan.

~~~
pfarnsworth
A treatment plan for a currently incurable disease? The only treatments
currently available (exercise, better lifestyle, etc) has minimal effects,
there is nothing that deterministically makes a material difference in the
progress of the disease.

~~~
Beltiras
If disease progression can be observed then a treatment plan can be devised.
Till now there has been a big problem making a hypothesis since early
detection has been hard.

~~~
pfarnsworth
A treatment plan that consists of what exactly? None of the treatments make
very much difference at all. A treatment plan filled with basically useless
treatments isn't much of a treatment plan.

~~~
Beltiras
Based on anything discovered with the patients found with the test. I imagine
a 15 year followup will reveal something.

------
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...](https://www.statnews.com/2017/08/18/beyond-amyloid-alzheimers-
research/)

------
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...](http://www.thelancet.com/journals/lancet/article/PIIS0140-6736\(15\)60461-5/abstract)

------
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.

------
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.

~~~
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.

~~~
dragonwriter
> 1/10 false positives doesn't sound too bad to me.

If the 15-year risk for the population taking the test is 10%, an unbiased 10%
error rate would mean:

81% true negatives, 9% false positives, 9% true positives, 1% true negatives.

> Even with a false positive, the changes you would make (lifestyle changes,
> brain stimulation, continuous monitoring) would only be beneficial

Not if prioritizing them crowded out things you could be doing to address a
real risk that is deprioritized because of the false result.

And, also, of course, an error rate doesn't have to be unbiased. With the same
population, a test with these results would also be 90% accurate:

90% true negatives, 10% false negatives.

------
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!

------
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!

