Three-Minute Take-Home Test May Identify Symptoms Linked to Alzheimer's Disease
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A new study suggests a three-minute take-home test may identify symptoms linked to Alzheimer's disease years before a traditional diagnosis, but commenters express skepticism about the test's effectiveness and the field of neuroscience in general.
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Meanwhile: the big challenge for screening tests is base rate confounding: the test needs to be drastically more specific the lower the percentage of the cohort that truly has the condition is. Relatively low rates of false positives can pile up quickly against true positives for conditions that are rare in the population.
The bad thing here is: you get a test suggestive of early-onset Alzheimers. It could realistically be the case that the test positive indicates in reality a coin-flip chance you have it. But that doesn't matter, because it will take years for the diagnosis to settle, and your mental health is materially injured in the meantime.
One correction here: the amyloid antibodies that successfully clear out a large amount of plaque have yet to report data from intervention trials prior to symptom onset, so we can’t say this with confidence and in fact we have good reason to suspect they would be more effective at this disease stage.
I wrote about this and related topics here: https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
Edited to add: the sort of test discussed in the OP wouldn’t be relevant to presymptomatic treatment, however, since it’s a test of symptoms rather than biomarkers for preclinical disease.
Have you seen the research in phase-targeted auditory stimulation, memory, amyloid, and sleep? Do you have thoughts on that?
Acoustic stimulation during sleep predicts long-lasting increases in memory performance and beneficial amyloid response in older adults - https://doi.org/10.1093/ageing/afad228
Acoustic Stimulation to Improve Slow-Wave Sleep in Alzheimer's Disease: A Multiple Night At-Home Intervention https://doi.org/10.1016/j.jagp.2024.07.002
I hadn’t seen that research, thanks for passing it along. It seems like an interesting approach to improve slow wave sleep, which is known to help with amyloid clearance.
Why is this pilot study in the Smithsonian?
I believe replication is key.
It was amazing when the room temperature superconductor paper came out about 18 months ago, the immediate response was to share the news, and then replicate.
I've seen studies that claim data from a nap is as good as data from sleep.
Sham's that don't compare the stimulation, for example how long it takes to fall asleep with stimulation AND the sound of waves compared to just silence. What happened to just the sound of waves?
What data is thrown out? We've seen studies which looks like the data which was removed didn't match the thesis. For example, when measuring how long it took a person to fall asleep, if they fell asleep too quickly in the sham condition, the data wasn't included, because they didn't have difficulty falling asleep.
But a big one I look for to clarify this is "why"? Why do we think this might work? What's the mechanism through which this is acting.
Even if it isn't 100% known, at least postulate as to why we think the body would respond in this manner.
With slow-wave enhancement, the theory is that we are triggering a protective mechanism in the brain, and in response the brain increases slow-wave activity. We see this clearly and immediately in EEG data right after stimulation, and for a few seconds after. We compare a 5-stim on/5 stim off within night stimulation condition.
I will admit that one of the challenges in sleep studies is that sleep is influenced by so many factors, and it isn't the same each night. Even with controls in place, this is VERY difficult to control for.
It is one of the reasons, as engineers, we like the stimulation we are working with. We can see the immediate brain response, and the research has shown the downstream neurological/biological/physiological responses as a result. Sometimes measured in real-time, such as cortisol and HRV, but when that is not available, next day responses.
The challenge to what we do is that the technology is difficult to implement, and the studies clearly show researchers struggling with this. I wrote about it in our blog post about Beyond Cherry Picking (https://www.affectablesleep.com/blog/beyond-cherry-picking-m...)
Sadly, our latest grant application did not receive funding, but we are supporting other clinical researchers with our technology. Our technology is based on more than a decade of research with 50+ published, peer reviewed studies.
We focus on sleep directly rather than the disease, which means people do not have to wait years for regulatory approvals before they can feel day-to-day benefits.
For those curious about learning more, our approach and links to additional research are on our website https://affectablesleep.com .
Mild-to-moderate Alzheimer’s changes in sleep https://doi.org/10.1016/j.jagp.2024.07.002
Slow-wave activity, memory, and amyloid response https://doi.org/10.1093/ageing/afad228
All the best on your research and funding. Quality sleep has been undervalued, especially among work cultures that value overachieving at the expense of personal health.
I don't think she's the first to postulate this, but I believe she is researching this relationship now.
Though work culture is an important one, we're somewhat more focused on the less self-imposed sleep challenges related to maternity and perimenopause/menopause.
Unintentional, but I like it!
> And accumulation of them is like a viscious cycle
I don’t know what this slip meant though ;-)
There was a comment on reddit a few days ago from someone with narcolepsy who was looking for a sleep tracker.
Sadly, our technology does not "induce" deep sleep.
It is suspected that the reason the Alzheimer's study showed such an increase in deep sleep was due to decreased cortisol as a result of stimulation, but that is just a theory at this point.
Studies do show a decrease in night-time cortisol (https://doi.org/10.1038/s41467-017-02170-3) early in the night during stimulation.
Is that what you meant? I assumed you meant from a privacy perspective.
Almost everyone on our team is on Android, but we wanted to iterate on the platform that most users are on and focus on getting that experience right.
Sales will somewhat depend on when we bring on someone to pick up the Android front-end.
We're a really small team, and with hardware, firmware, services, and apps, the engineering footprint becomes quite large.
What often doesn't get factored in is manufacturing test rigs, plus we have software to support clinical research.
I'm not complaining about it, but holding off on Android seemed to be the right move, as we can't remove any of the other functions. We've had quite a few requests for Android.
If the toilet was invented today, plumbers would all be telling us how $1/shit is a steal.
Much less if you want to build it yourself.
https://www.indiatoday.in/trending-news/story/china-toilets-...
I've made a post on HN for context https://news.ycombinator.com/item?id=45338308
Just red flags everywhere.
On our site we simplify the language. That is partly because of the regulations do not allow us to make clinical claims prior to approval, and partly because explaining the neuroscience in detail would overwhelm most visitors.
I link to the research so those interested can dive in deeper, and that is allowed.
The build-up isn't scarring. It's misfolded proteins in the brain which stick in places they shouldn't and the glymphatic system which flushes cerebrospinal fluid through the brain removes the build-up of these protiens.
If you have poor sleep or lack of sleep, these proteins don't get removed and that build-up interferes and disrupts the firing of neurons.
Alzheimer's drugs are able to help remove the build-up, but unfortunately are not able to repair the damage. That's why they only slow progression of the disease, not treat it.
If slow-wave enhancement lives up to the potential, it would likely also only be preventative. It would be surprising if it was able to treat AD.
If you want to know more, a comment in this post has what I think may be the most thorough breakdown of AD. https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
Startups are hard at the best of times, hardware startups are harder. When the company making the hardware inevitably goes under, you are left with a useless piece of plastic that you paid a ton of money upfront for, and then paid a hefty sum every month on top.
The reason we use a subscription is to keep the upfront cost much lower. It's important to us that we make better sleep as accessible as possible. A one-time payment makes that more challenging at this stage.
We also wanted to keep things simple at checkout. Too many options can be confusing, and at this early stage our priority is making it straightforward for people who want to try the technology.
It's a delicate balance.
From my side as a customer, here's what I would need to see before supporting you:
1. A one off payment to own the current version of the device. This must include the ability to download all of my data that I generate from using the device. It can be in raw, unporcessed form.
2. A subscription is acceptable but would pay for cloud based data processing, generating reports etc. Processing and storing my data, in other words
3. A clear privacy policy stating that you will never sell my data in either raw or processed form. But I assume as a medical device that's already in place?
We'll be clearer on the privacy policy. We're not yet regulated as a medical device.
The data download has been discussed, it's not currently in the product.
We actually take a different approach on the subscription. The processing of your sleep data itself is included with the device. It's the stimulation, which we believe is where the value is, which the subscription covers.
Of course there is extra processing with the stimulation as well.
We're not there yet on downloading of data. It's been discussed, and we currently provide raw data to researchers. So few people would know what to do with raw EEG data. We've seen other companies provide EEG downloads in the past, only to remove the feature, and we'd like to have a better understanding of why.
I know from my previous start-up, supporting data download added support overhead, and that was just location data.
Ugh. Just say "recurring revenue". We're not naive.
To help you a bit: 1 is easier… So 1 hardware product working independently is what we want. If you must to appease the shareholders do a subscription…make it add some functionality that would be impossible without a subscription… But locking people in a subscription to “keep upfront cost lower” is devious at best. Add to the world..don’t (cash)grab.
We've taken it to heart and have decided to run a test with a one-time payment, currently only really available to HN.
The context is at https://news.ycombinator.com/item?id=45338308
Your first FAQ answer begins extremely apprehensively. Is that even the number one most frequently asked question? I would suggest heavily revising that answer or getting rid of it completely.
Many devices today support dark mode, such as my S24. The website does not display clearly in this mode.
On dark mode, we deliberately avoided it. Most sleep products lean into dark, sleepy visuals, which makes sense if the goal is to help people fall asleep or stay asleep. Our product doesn’t do that, so we are careful not to give the impression that it does, even though sleep is at the center of what we build. Our hope is that the brightness of our brand doesn’t mislead people, or lets us prevent them from misleading themselves.
Does that make sense?
Dark mode however is just an accessibility concept, not really about aesthetics. For some people they work hard to make it aesthetically consistent. But honestly I think dark mode compatibility should not have to be a perfect replication
Like other readers, I saw the subscription business and got put off.
Especially since it seems that every company eventually either "enshittifies" or goes on an "incredible journey".
We have no aim to "enshittify", I'm actually not sure what an incredible journey is? Can you elaborate on who has gone on such incredible journey's?
I wonder if some of the enshitiffication is a result of investor demands (as another comment alluded to).
We're doing our best to bootstrap Affectable. Bootstrapping a neurotech hardware start-up is not easy, and it's a bit of a miracle we've mostly managed so far.
Thanks for your input, and your early support. I'd be keen to know if there were other details you'd like to hear about on our mailing list.
We'll keep reviewing our pricing model based on feedback. We do appreciate you taking the time, and for your consideration.
https://ourincrediblejourney.tumblr.com/
Blog posts from startups who get acquired by big companies, talking about what an incredible journey their startup has been, and thanking their customers and promising ongoing support for their products. And then breaking these promises soon after.
And no one aims to enshittify, but my understanding is that pressure from investors eventually becomes louder than that from customers. (Although perhaps less so in your case, as you say you're bootstrapping.)
If you have a subscription model, you're asking me to trust you over the long term. But, if I understand your product correctly, there's no technical reason why I need to have an ongoing relationship with you or even an internet connection to use your product. Those are apparently business decisions. And I'm afraid those are decisions which lead me to trust you less.
The reality is that without a subscription, the product would not be viable. We would either have to charge nearly double upfront, or risk not being around to support it in a few years.
The subscription lets us keep the starting cost lower, which makes the tech inaccessible for many people. The subscription balances that out, and it also means we can keep supporting the system over time instead of leaving people stranded.
In a sense, it is actually what makes the long-term viability and hopefully trust possible.
That's how we view it.
For example, if you read Slate Star Codex, you can find all manner of posts discussing how psych meds are produced and brought to market, how they can behave in unpredictable fashion, and why claims made by the pharmaceutical industry should be regarded with a healthy dose of distrust. But its author is a trained psychiatrist, and he'd be the first to tell you that psych meds do indeed work.
Personally, I've dealt with sleep issues for years with reasonably consistent symptoms. I read various books and tried CBT, therapy, and a variety of meds. A lot of this seemed to either do nothing, or else have strange effects. Eventually I tried some med that got terrible reviews online, which to my surprise pretty much solved my problem overnight. Now I'm overseas for several months without access to this medication, and to my complete surprise my sleep has been fine. Why? Will things stay this way? I wish I could tell you!!
All this is to say, for your target market, suspicion and distrust will often be par for the course. Please don't take it personally :)
Not taking it personally at all!
I'm a life-long chronic insomniac, which is how I got into this.
My first reaction wasn't "I'm going to solve this problem", it was
1) is this slow-wave enhancement even real 2) will anyone believe it 3) who is it for? How do we prove it?
I had some confidence in slow-wave enhancement because Philips did a bunch of research in this space and tried to launch a product and failed.
But the researchers that worked with Philips were at University of Sydney (where we work) and Melbourne, so I had access to some of the top researchers in the world.
Also, one of the first researchers I spoke to said he was amazed by the technology, but then I discovered he secretly hated it. He didn't make excuses for why it wouldn't work. He said it did, but made excuses for why we couldn't do it. Why it wasn't safe (which has been proven wrong). That made me go "wow! This guy could have said it doesn't work, but he didn't. He said it works, but we don't know the impact on respiratory function, immune function, etc etc. " That was a powerful moment for me.
Then I spoke to some local VCs and med investors I know, thinking, I'm going to need funding, will they just ignore us? One said "this is exactly the sort of thing he looks for". Then they ghosted us, but I sold my other start-up and we funded this :)
Lastly, the who is it for....this is the one Philips really struggled with. I think it's the biggest challenge for us.
You mentioned your insomnia. We're not an insomnia device. But everyone hears "better sleep" and thinks fall asleep faster, sleep longer. That is a difficult pattern to break out of.
I still have insomnia. I'll tell you what is not the cure...bootstrapping a neurotech hardware start-up! :)
My belief is that if we stay true and honest about our capabilities, focus on the people we can help, and change the story about sleep.
From that base, we can look to continue to expand and help others.
I've written about some context here https://news.ycombinator.com/edit?id=45338308
I ask as someone who has sleep apnea and uses a CPAP machine.
Do you feel your CPAP improves your mental clarity, or mood?
The reason I ask is the cognitive benefits of CPAP are inconclusive. It works in some people, not in others. It solves the hypopnea, but that doesn't mean slow-wave activity increases as a result.
There is no research I'm aware of that has been published showing how slow-wave enhancement impacts people with sleep apnea.
We work out of The University of Sydney, where CPAP was invented and work with a few former ResMed employees, and know a bunch of people who still work at ResMed.
When we approached them a few years ago, they didn't seem very interested, but the science has progressed significantly since then, and it's getting pretty difficult to ignore it.
I'll reach out and see if they're keen on supporting a study.
BTW, have you tried a mandibular splint (biteplate)? My brother was on CPAP for about 8 years, and then moved to a moved to the biteplate about a year ago. He's MUCH happier with it.
It's correlated eith amnestic MCI, ehich itself correlated with higher risk of alzheimers(edit0:typo) (that's what I'm reading from the begining of the paragraph you quoted)
> linked to
Really putting their necks on the chopping block and making with the bold opinions, here.