
Why I’m Digging Deep Into Alzheimer’s - tuxguy
https://www.gatesnotes.com/Health/Digging-Deep-Into-Alzheimers?WT.mc_id=11_13_2017_00_Alzheimers_BG-EM_&WT.tsrc=BGEM
======
bflesch
It's great to see more investment into this disease.

When my grandma fought Alzheimer's over the span of a decade it was very
striking to see that the effect of a lack of hydration and the disease itself
kind of overlapped. When she had a particularly bad day we used to give her a
saline IV and you could immediately notice how she cleared up and regained her
brain powers after each IV.

I'm not up to date on current research into that direction, but I think
hydration plays a very big role in Alzeimer's symptoms on the elderly.

I know it sounds ridiculous, but once I'm rich enough I want to build an
elderly care center/hospital with urine-based hydration monitoring for each
participant so family members can be sure that their loved ones have a healthy
water intake each and every day.

~~~
taf2
I think the toilet in general could use an upgrade... for how many years have
they been built exactly the same way? Has anyone ever done a study of the flow
as urine impacts the toilet and bounces back? Or as we learn more about the
importance of stomach bacteria, can our toilet start to do more monitoring of
the bacteria in our stomach? Love your idea of hydration monitoring and think
the application is probably more far reaching than just Alzheimer’s

~~~
bflesch
Yes, I think it makes more sense to monitor and gather data on what comes out
of your body instead of monitoring what goes into it(e.g. all
smartwatches/diets).

I'd like to one day have a room-sized analysis unit which screens feces/urine
of all attached toilets and performs various tests on it. Analysis results
could be assigned to individuals based on the DNA footprint.

It could immediately tell you that your sugar intake is too high or that you
should drink more water. With this kind of immediate feedback people will be
able to live healthier because they can correlate food <-> result on their
body.

Also we could do so many interesting studies..

~~~
StudentStuff
It'd be great to be able to pull glucose, hydration and more out of urine
samples real time, so long as we stay away from say live telemetry to insurers
or something like SmartPipe[1] it'd be enormously beneficial.

1 -
[https://www.youtube.com/watch?v=DJklHwoYgBQ](https://www.youtube.com/watch?v=DJklHwoYgBQ)

~~~
bflesch
In health this would be massively beneficial. Imagine a digital hospital where
you monitor excrements for every patient during their stay. When my father was
in the stroke unit recently they had him drink a shitload of water and they
monitored water intake by making him write down how much he drank and when.

Stupid thing is I need a 100M exit first to sponsor this kind of thing.

~~~
zafka
I do not think you need an exit to sponsor this. How about starting a web site
that outlines all your ideas? Start building interest in the idea. Invite
discussion.....

------
_Marak_
It's interesting to note that tetrahydrocannabinol and other compounds found
in marijuana may reduce the amount of beta amyloid in the brain. Beta amyloid
is commonly thought to cause Alzheimer's disease.

see:
[https://www.nature.com/articles/npjamd201612](https://www.nature.com/articles/npjamd201612)

Last I heard in the US, the Federal government was still making it difficult
to run clinical trials for Alzheimer's using marijuana. I think any federally
funded medical trial using marijuana needs to be approved by the DEA.

~~~
Beltiras
It's more complex than just that. At CTAD just a couple of weeks ago there was
a presentation on drugs that managed to reduce AB (biomarker was inferred by a
PET scan) and it did not result in increased cognition.

~~~
eganist
A simple hypothesis which could explain this might be that the plaques cause
effectivelt permanent brain damage. The question is whether degenerative
patterns ceased or slowed after substantial clearing of plaques from the
brain.

I would expect this test (and therefore the hypothesis) to fail if the plaques
themselves are a byproduct rather than the cause of degradation in brain
function. That said, I'm surprised I haven't read much in Gates' Notes or
other funding sources on potential ties to HSV1 considering all the
increasingly supportive research between the two.

~~~
JamesBarney
They used several techniques that clear beta amyloid from the
brain.(antibodies and ultrasound). And they've have little if any effect on
cognition. I'm starting to think beta amyloid is a red herring, or maybe just
important in the prodromal stages of the disease.

------
judah
Michael Fossel and his biopharmaceutical company Telocyte claim[0] to have a
novel, effective treatment for Alzheimers, one that does not simply target the
amyloid and tau pathways. Telocyte's treatment is based on telomerase gene
therapy, and is currently undergoing FDA safety trials.

According to Fossel, their telomerase gene therapy reverses cognitive decline
in animal models, and they're confident the same will apply to humans. Human
trials begin in 2018.

I wonder whether Gates has seen Telocyte's work.

[0]:
[http://www.michaelfossel.com/blog/?p=249](http://www.michaelfossel.com/blog/?p=249)

------
leekyle333
The Buck Institute has been doing a lot of great research on alzheimers. They
are taking a very different approach though. Tinkering with everything from
diet, to infections, to heavy metals, to hormone optimization. Here is a good
podcast with one of the main researchers from the Buck Institute.
[https://www.youtube.com/watch?v=HS7VZydS8HI](https://www.youtube.com/watch?v=HS7VZydS8HI)

It's crazy how much focus has been on clearing amyloid without much luck at
all. 224 clinical trials and only 2 drugs going through.

------
Beltiras
I work for a company[1] in this space. We make software that analyses EEG
recordings and predicts if the subject will develop Alzheimer's. We are
currently working on Class 2 CE mark for our AD product.

[1]: [http://www.mentiscura.com/](http://www.mentiscura.com/)

~~~
docere
Is this promising tech? EEG may be sensitive but not very specific.

~~~
Beltiras
Wouldn't be working on it if it weren't. I can't go into specifics.

------
Nomentatus
Funny, I remember contacting the Gates foundation many years ago now about
chronic illnesses and the then-new discovery of ipRGCs/pRGCs (which we will
find have a critical role in Alzheimer's) and hitting a total brick wall.
Paraphrasing them, "this wouldn't help the third world" \- we know better now.

~~~
reasonattlm
The burden of aging falls most heavily on the poor, though it has to be said
that the differences between rich and poor are small in comparison to the
absolute degree of harm done by aging.

It has been a disappointment to see the Gates Foundation near entirely bypass
this area of research up to fairly recently, presumably because they do hold
this strange view of aging being either a non-issue, or a problem of wealthy
regions.

From a utilitarian perspective, nothing that goes on in the poorest parts of
the world rises to the level of harm done by age-related disease. Not even
close.

~~~
vidarh
The point, though, is that there is a whole lot of wealthy older people who
can or do put money into research on aging related problems, exactly because
it affects rich people too.

There is no danger that aging will be overlooked.

------
reasonattlm
The slow pace of progress towards clearance of amyloid, in that only in the
past year has one of the immunotherapy trials actually looked promising, has
provoked a lot of alternative theorizing these past five years. Some it is
clearly not so great, such as the fellow who argues that it is caused by
rising use of paracetamol (see
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921468/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921468/)
), but some lines of theory are much more compelling. A more encompassing
synthesis is emerging in which microbial infection by spirochetes and gum
disease bacteria (e.g. see
[https://doi.org/10.3389/fnagi.2017.00336](https://doi.org/10.3389/fnagi.2017.00336)
) that can provoke amyloid formation as well as failing drainage of
cerebrospinal fluid (e.g. see
[https://doi.org/10.1002/ana.24271](https://doi.org/10.1002/ana.24271),
[https://www.ethz.ch/en/news-and-events/eth-
news/news/2017/11...](https://www.ethz.ch/en/news-and-events/eth-
news/news/2017/11/exit-through-the-lymphatic-system.html), etc) that stops
removal of amyloid, tau, etc are as important as purely cell focused
considerations of the biochemistry of amyloid beta.

For an example of the new type of venture emerging now as a result of all of
this you might look at Leucadia Therapeutics, working on a way to restore
drainage through the cribiform plate, but there will be more in the years
ahead to complement the immunotherapy for amyloid and tau mainstream.

~~~
Mr30
>> A more encompassing synthesis is emerging in which microbial infection by
spirochetes and gum disease bacteria

Wow, I did "notice" a strong correlation between gum disease and dementia in
my own Family. This is obviously my own uneducated guess but it's humbling to
see serious people looking into it! There very well could be some sort of
dementia that is indeed related to gum disease!

~~~
redcalx
I believe gum disease is also correlated with cardiovascular disease.

------
louprado
The documentary "Under our Skin" details Alan MacDonald's breakthrough
research on how Lyme disease causes Alzheimers. The 4 minute trailer is worth
a watch[1], but basically Lyme disease is found in 7 or 10 brains of
Alzheimers patients (small sample set). The Lyme disease spirochete literally
drills countless pathways in the brain and that causes slow dementia. That
spirochete also creates a biofilm which makes it challenging to detect in a
living patient. His research is from a decade or two ago.

Also I wonder how a citizen scientist like Gates does a deep dive on this
topic a like this. There are 10's of thousands of research papers on the
subject[1] and countless books.

[1]
[https://www.youtube.com/watch?v=GCLwauRh2gQ](https://www.youtube.com/watch?v=GCLwauRh2gQ)
[2]
[http://archive.sciencewatch.com/ana/st/alz2/journals/](http://archive.sciencewatch.com/ana/st/alz2/journals/)

~~~
joewee
Re Gates; he and his staff identify Subject Matter Experts (SME) for the
topics he’s interested in. As you can imagine he has a good network. SMEs are
always looking for funding, so he’ll use one of his funding vehicles to invite
the SME to apply for funding or meet with the organization. By the time you
meet with Bill Gates he would have read your most recent papers and competing
theories and will be prepared to challenge you on your approach. Pass his
final intellectual test and you are added to his collection of SMEs. <source:
me, I’ve seen the process>

Edit: When I had the pleasure of watching Bill Gates do this, it was one of
the most impactful moments in my life. When he would question a SME on a topic
he came across as knowledgeable as the SME who has dedicated years to the
topic. Bill Gates literally will have read all around the topic and his mind
operates like a poker player or chess player who is thinking on multiple
levels. His questions are probes to see how many levels you are thinking on,
and I think it also informs him of other angles. He’s a brilliant guy.

~~~
skybrian
SME seems be "subject matter expert".

~~~
pouetpouet
I think it's "small and medium-sized entreprises" aka SMB

------
amelius
> We need to use data better. Every time a pharmaceutical company or a
> research lab does a study, they gather lots of information. We should
> compile this data in a common form [...]

We could use all sorts of data, not just from research or pharmaceutical
companies. Is there an overview of what data is available or planned for, from
clinical to commercial? And what data-integration platforms are planned for? I
suspect many countries are trying to invent this on their own, while a world-
wide approach could yield better results.

~~~
komali2
How do you motivate a pharmaceutical company to share R&D they spent millions
acquiring?

~~~
nitrogen
Require it for FDA approval

~~~
mark-r
The flaw in that plan is that they'll share it in the most unhelpful way
possible. See: Patents.

~~~
amelius
Solution: let the data gathering be done by the FDA (or subsidiary).

------
maxst
>Most of the major pharmaceutical companies continue to pursue the amyloid and
tau pathways. Dementia Discovery Fund complements their work by supporting
startups as they explore less mainstream approaches to treating dementia.

That's very encouraging. Because what if it's something else?

~~~
Filligree
The amyloid and tau pathways are our best hope of finding a _simple_ solution,
something we can reasonably fix with drugs.

If it's something else, then chances are good it'll be far harder to fix,
perhaps even requiring genetic engineering or medical nanotechnology. Finding
out is still valuable, of course...

~~~
hprotagonist
We’re batting 000 on drugs that target amyloid or tau, and not for want of
trying.

~~~
Filligree
Fortunately, we have enough resources to try multiple approaches.

I'm happy that we're doing so. For a very long time this was treated as just a
fact of life, immutable.

------
ggambetta
Cynical answer: "because I'm getting old" :)

Whatever the reason, this has the potential of being life-changing for a lot
of people. Would love to see more billionaires involved with this kind of
initiative.

~~~
Filligree
The reason doesn't really matter, this is still incredibly valuable work.

Death is terrible, and should be eradicated, but Alzheimer's is a few steps
above that. There's _nothing_ worse than seeing a loved one be slowly
destroyed by that horrific disease, and I'm so glad there are people willing
to work on it.

~~~
pmelendez
"Death is terrible, and should be eradicated"

We are sensitive to death but it is the only mechanism I know that would
control overconsumption of natural resources. If nobody dies, then we would
deplete the resources in a few decades.

~~~
sheepdestroyer
We have death and at the same time over-consumption, so the control is not
working that well. Did you mean that it would effectively control the over-
consumption if better implemented (with a higher rate)?

~~~
freeflight
Parent merely stated that we are already over-consuming with rather high death
rates, not having any deaths at all most certainly wouldn't help with our
current unsustainable ways, as we'd most likely overpopulate the planet pretty
quickly with all it's resulting woes (even more pollution, killing off the
rest of the biosphere).

Imho it'd only work the other way around: For us to beat death, we first have
to solve our sustainability/resource problems. What point is there to
"endlessly living" if the reality of that boils down to being stuck in
overcrowded and miserable living conditions? That sounds more like hell than
utopia.

~~~
Filligree
You're making the mistake of changing one parameter, but not projecting the
entire world forwards. Immortality would be impossible without massive
technological improvements that certainly would have other benefits; you can
pretty well assume that both molecular nanotechnology and genetic engineering
will be mature by then.

In combination, those should dramatically increase the carrying capacity of
the world.

Ignoring all of that, though... Don't you think it's likely that people will
start caring more about the future onceb they know they'll live to see it?

~~~
coldtea
> _Immortality would be impossible without massive technological improvements
> that certainly would have other benefits; you can pretty well assume that
> both molecular nanotechnology and genetic engineering will be mature by
> then._

I don't think we'll see anything like increased exponential progress of the
kind that has been (and has already slowed down) during the industrial age.
All low hanging fruit have been gathered, and at this point there are
diminishing returns.

We will have a few breakthroughs here and there but nothing to write home
about the way the steam engine, electricity or the computer have been.

> _Ignoring all of that, though... Don 't you think it's likely that people
> will start caring more about the future once they know they'll live to see
> it?_

Most people are terrible managing their own lives a few years ahead, much less
decades ahead. So no reason to think they'll be any more apt when its
something so vague as centuries ahead.

~~~
melling
Then we probably won’t cure death without large technological improvements.
Problem solved.

This conversation is going in circles. Has anyone brought up “death gives life
meaning”?

[https://h4labs.wordpress.com/2017/03/28/stories-that-
should-...](https://h4labs.wordpress.com/2017/03/28/stories-that-should-be-
banned-from-hacker-news-immortality/)

~~~
Filligree
> This conversation is going in circles. Has anyone brought up “death gives
> life meaning”?

A platitude uttered by people who believe they have no way out, and are
desperate to make themselves feel better about that. Not necessarily a bad
thing, _so long as there really is no way out_ , but catastrophic once that
changes.

Destroying death will lose us something, most certainly; there are any number
of great works of art and philosophy that would never have been created
without the pressures and emotions it creates. But none of that, I think, can
even remotely make up for the sheer awfulness of the downside.

There has to be a better solution than this creeping horror.

~~~
melling
I imagine immortality will be optional. If it creeps you out, there will be
other options...

~~~
vidarh
The Metamorphosis of Prime Intellect [1] (full text available for free; be
warned it's extremely violent and sexual) is an interesting novel where
immortality is not optional:

An AI was "let loose" with a variation of Asimovs laws of robotics, and
interpreted the requirement not to let anyone come to harm through inaction as
requiring it to literally end death.

The main character is a woman that feels it left her life without meaning, and
who in response started gruesome competitions involving designing the most
outrageous ways to die. Or rather, getting as close to the moment of death as
Prime Intellect will let them before reviving them.

[1] [http://www.localroger.com/prime-
intellect/](http://www.localroger.com/prime-intellect/)

------
yitchelle
Just relistening through some of RadioLab's podcast. I came across this apt
episode about Gamma Light Therapy. Adding it to the mix. When I listen to this
episode, I had a hint of hope for my dad who is suffering dementia in the past
few years.

[http://www.radiolab.org/story/bringing-gamma-
back/](http://www.radiolab.org/story/bringing-gamma-back/)

~~~
new299
It seemed like such a simple treatment, that it should be relatively easy to
test more widely... But whenever I've searched, I've not seen an update.

For those who haven't listened to the podcast, the treatment is effectively
just being exposed to a 40Hz (IIRC) flashing light. Which sounds surprisingly
simple.

------
gk1
Even younger people can be afflicted with Alzheimer's (called Early-onset
Alzheimer's), and it's even more terrible to witness. It's one thing to watch
a human mentally deteriorate when they are at the end of their life, it's
another thing to watch it happen to someone in their 40's—who should be in the
prime of their life and raising their children.

~~~
yeukhon
Yes. The thing is once you are an Alzheimer's patient, you are doomed because
your brain basically stop being able to function at the very end. It's like a
death kiss from the above. Unlike cancer, which is scary as hell, and has a
high death rate, has better chance of surviving. The pressure on Alzheimer's
patient and on the family is just unbearable. While there are some treatments
to slow down the progress, we are far from understanding the disease itself,
let alone knows how to combat the plaque and tangles effectively. Right now I
think one of the best treatments is let patients be more active, whether it's
playing chess or gardening, while receiving family support. The more positive
we are the better we are overall health wise. This is evident in patients who
suffered depression.

------
mhkool
Dear Bill, to spend money wise and efficiently I suggest that you look at the
work of Dr Dale Bredesen. Dr Bredesen has fantastic results with his Alzheimer
treatment and has published about it. In short, his treatment cures 9 out of
10 patients with mild Alzheimer. His scientific work is solid and a larger
study is currently done. Check it out!

~~~
djohnston
I've been interested in his work, but discouraged by the case-report based
evidence. Can you link me to this larger study?

~~~
mhkool
sorry, no link. It was said in a video and I am not 100% sure but I believe
that part of the study is done at the Cleveland Clinic.

------
melling
His first donation is $50 million to this private organization:

[http://theddfund.com](http://theddfund.com)

------
raleec
I remember that ultrasound[0] was very promising a few years back. Does anyone
have any more recent info?

[0]: [http://www.sciencealert.com/new-alzheimer-s-treatment-
fully-...](http://www.sciencealert.com/new-alzheimer-s-treatment-fully-
restores-memory-function)

------
dawhizkid
I believe there are already studies out there that link excess sugar intake
with increased risk of Alzheimer's?

I think this is yet another case for a ketogenic diet/intermittent fasting...

------
jwilk
Archived copy, which can be read with JS disabled:

[https://archive.is/rDJ6G](https://archive.is/rDJ6G)

------
nonbel
Emphasis added:

>"Most drug trials to date have targeted amyloid and tau, two proteins that
_cause_ plaques and tangles in the brain."

This is assumption, not fact:
[https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-...](https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-014-0169-0)

------
yhvh
[https://www.brainwavebank.com/](https://www.brainwavebank.com/)

------
arghwhat
Heh, the blog fails to load in Firefox 57...

~~~
Jhsto
Same thing (the text does not appear) happens if you have Ghostery on blocking
all the trackers.

~~~
bahjoite
Same. And with nearly thirteen thousand lines in the source of the page you'd
think the text would be there too.

edit: oh, there it is, 25 lines beginning at line 8201.

~~~
noir_lord
> oh, there it is, 25 lines beginning at line 8201.

This comment made me laugh with the tragedy that is the modern web.

------
Carhughes
I love that Gates is driving money into this needed area. We need new ways of
attacking cures and the tech arena should be the driver not science. IMO,
traditional science has gotten in the way and their agenda isn't where it
needs to be: to find a a cure and save lives (take cancer research for
instance).

~~~
Eridrus
I don't understand why you think tech companies will be any better at this
than biomedical companies. All businesses have the same incentives to make
things chronic issues (subscription revenue!) rather than curing them.

~~~
Carhughes
Because I recently read a really interesting story that talked about how
science tends to get in the way of real progress. I hope you don't mind me
sharing it with you but it struck a real note with me.
[http://www.thenewatlantis.com/publications/saving-
science](http://www.thenewatlantis.com/publications/saving-science)

------
nikolay
The new research [0] on similar causes of diabetes, Alzheimer's, and cancer is
exciting as one could target major killers at once.

[0]:
[https://www.youtube.com/watch?v=KSo-p7DafpA](https://www.youtube.com/watch?v=KSo-p7DafpA)

------
marze
Say you had a $80 million dollar budget. How would you deploy it to have
maximum impact on Alzheimer’s?

In other words, what would you do if you were in Gates position?

------
knodi
Alzheimer is essentially type 3 diabetes. I'm happy to see Gates behind this.

~~~
richardwhiuk
What?

~~~
arikr
I'm guessing they mean because it may be related to insulin resistance / sugar
consumption, but I'm not sure.

------
rikelmens
Prevention, prevention, prevention.

------
vasco
Disable the shitty auto-pausing of youtube video on scroll by pasting this on
the console:

    
    
      getEventListeners(document.getElementById('tgnbody')).scroll.forEach(function(el){document.getElementById('tgnbody').removeEventListener("scroll", el.listener)})

~~~
tzahola
Thanks!

I'd love to have a browser extension which automatically augments shitty
websites with community-sourced javascript snippets. E.g. you'd visit idk
Forbes.com, and saw that the site is unusable b/c of some shitty undismissable
paywall overlay. You "fix" the issue with a few lines of JS, and then upload
it via the extension. After going through some kind of vetting/review, the
extension will automatically fetch and run your JS fix for everyone who visits
the site.

~~~
robbyt
Grease Monkey?

~~~
tzahola
Does GreaseMonkey suggests you scripts based on the current site you're
visiting?

------
madshiva
no need to have Alzheimer to see these poor old guy / women that can't do
anything. We should die sooner, waste less resource and enjoy more.

~~~
Chris2048
What would you suggest?

~~~
madshiva
Don't extend life...we discovered these things because we are older and older.
I don't think that the solution is getting older. Don't know why I'm always
getting down vote too. Life and his mystery.

~~~
Chris2048
What about the elderly people who don't have problems?

------
xkcd-sucks
Finally, a cause that can eat up the entire Gates fortune without breaking a
sweat

------
bitL
FYI, taking sauna 4x a week seems to lower the risk of developing Alzheimer
significantly (at least in Finland). I can also observe myself that taking hot
phase 4-5x for 10-15 minutes followed by 2 minutes cold immersion every time
in roughly 1.5 hours clears my brain/senses. Maybe the sweating helps
overloaded brain drainage as well?

I think Bezos must be applying some of these hacks on himself; he got recently
in shape while in previous decades he seemed to let himself go. Bill might
think about the same as he is visibly deteriorating and his liver seems to be
not functioning well (spots on his skin everywhere). They should add calorie
restriction/frequent fasting as well. It's unlikely they will beat the death,
but might make their final moments less horrible.

~~~
tallanvor
Liver spots are the result of aging sun exposure. A long time ago they were
thought to indicate an issue with the liver, but there is no connection
between the two. They are not at all an indicator of health. The only affect
they have medically is that they can make it harder to detect skin cancer when
doing a visual exam.

~~~
bitL
Thanks, I'll update my knowledge :)

