6 ms·

Three-Minute Take-Home Test May Identify Symptoms Linked to Alzheimer's Disease

116 points by pseudolus 1y ago

tptacek 1y ago
The standard statistical caution for these kinds of screening tests is especially important here, because while Alzheimers drugs may be more effective earlier in the disease course, none of them are "effective" in the sense of meaningfully staving the disease off; the upside to early detection is not very strong. 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.
- DavidSJ 1y ago
  while Alzheimers drugs may be more effective earlier in the disease course, none of them are "effective" in the sense of meaningfully staving the disease off; the upside to early detection is not very strong. 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-hypothesis 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.
  - pedalpete 1y ago
    That is an amazing breakdown of AD, and I think it will be my go-to for sharing in the future. 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 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 https://doi.org/10.1016/j.jagp.2024.07.002
    - DavidSJ 1y ago
      Thank you for your kind words. 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.
      - pedalpete 1y ago
        If you're looking into this space further, I've posted the majority of the research on our website https://www.affectablesleep.com/how-it-works https://www.affectablesleep.com/how-it-works (bottom of the page)
- hollerith 1y ago
  Your first sentence seems to imply that an effective intervention or treatment for AD would need to be a drug.
- Retz4o4 1y ago
  What about Alpha Cognition’s Zunveyl?
dr_dshiv 1y ago
Exercise significant skepticism with neuroscience. People are credulous — and many studies are honestly shams. Like that “MIT study shows that ChatGPT reduces brain activity.” Why is this pilot study in the Smithsonian?
- pedalpete 1y ago
  I tend to agree with you, and many sleep studies are even worse. I work in the space. 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.
  - macintux 1y ago
    In fairness, as I understand it room temperature superconducting would change everything. Small wonder people were excited.
  - dr_dshiv 1y ago
    What to watch for in the sleep space?
    - pedalpete 1y ago
      There's a lot of nuance that you kind of learn to sniff out. 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-making-sense-of-mixed-results-in-sleep-research https://www.affectablesleep.com/blog/beyond-cherry-picking-m...)
pedalpete 1y ago
There is a growing body of research showing that increasing slow-wave activity during sleep can improve outcomes, including sleep quality[1], memory, and correlations with amyloid response[2]. 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 https://affectablesleep.com . Mild-to-moderate Alzheimer’s changes in sleep https://doi.org/10.1016/j.jagp.2024.07.002 https://doi.org/10.1016/j.jagp.2024.07.002 Slow-wave activity, memory, and amyloid response https://doi.org/10.1093/ageing/afad228 https://doi.org/10.1093/ageing/afad228
- DaveZale 1y ago
  yes, poor sleep quality leads to bad days, bad days lead to more bad sleep, it is a downward spiral and may impact many of us in our prime years, too. 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.
  - pedalpete 1y ago
    Thanks. A researcher we work with has postulated that build-up of metabolic waste (amyloid and tau, among others) directly impairs the glymphatic system, leading to more build-up. A viscous cycle. 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.
    - DaveZale 1y ago
      that's a cute Freudian slip (or deliberate joke) - viscous cycle - sure, amyloid and tau are probably very viscous when you poke at them with the laboratory utensil of your choice. And accumulation of them is like a viscious cycle of plaque accumulation and even worse clearance. It seems exponetial
mcswell 1y ago
I am not understanding this: "It can’t directly predict who will develop Alzheimer’s, but it does identify who could be at a higher risk." I get the part that it can't "directly predict", but what does it mean to "identify who could be at a higher risk"? How was "higher risk" independently diagnosed in the study in order to show a correlation between higher risk according to this test, and higher risk according to some other test?
- dmbche 1y ago
  "Patients with amnestic MCI—who have memory loss as their main symptom and are more likely to develop Alzheimer’s compared to people with non-amnestic MCI—had lower responses to the test, reports the Guardian’s Ian Sample. It can’t directly predict who will develop Alzheimer’s, but it does identify who could be at a higher risk." 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)
kingofmen 1y ago
> may identify > linked to Really putting their necks on the chopping block and making with the bold opinions, here.
sujit1779 1y ago
[dead]
nextrastapasta 1y ago
[dead]

116 points by pseudolus 1y ago

The standard statistical caution for these kinds of screening tests is especially important here, because while Alzheimers drugs may be more effective earlier in the disease course, none of them are "effective" in the sense of meaningfully staving the disease off; the upside to early detection is not very strong. 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.

DavidSJ 1y ago
while Alzheimers drugs may be more effective earlier in the disease course, none of them are "effective" in the sense of meaningfully staving the disease off; the upside to early detection is not very strong. 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-hypothesis 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.
- pedalpete 1y ago
  That is an amazing breakdown of AD, and I think it will be my go-to for sharing in the future. 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 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 https://doi.org/10.1016/j.jagp.2024.07.002
  - DavidSJ 1y ago
    Thank you for your kind words. 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.
    - pedalpete 1y ago
      If you're looking into this space further, I've posted the majority of the research on our website https://www.affectablesleep.com/how-it-works https://www.affectablesleep.com/how-it-works (bottom of the page)
hollerith 1y ago
Your first sentence seems to imply that an effective intervention or treatment for AD would need to be a drug.
Retz4o4 1y ago
What about Alpha Cognition’s Zunveyl?

dr_dshiv 1y ago

Exercise significant skepticism with neuroscience. People are credulous — and many studies are honestly shams. Like that “MIT study shows that ChatGPT reduces brain activity.” Why is this pilot study in the Smithsonian?

pedalpete 1y ago
I tend to agree with you, and many sleep studies are even worse. I work in the space. 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.
- macintux 1y ago
  In fairness, as I understand it room temperature superconducting would change everything. Small wonder people were excited.
- dr_dshiv 1y ago
  What to watch for in the sleep space?
  - pedalpete 1y ago
    There's a lot of nuance that you kind of learn to sniff out. 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-making-sense-of-mixed-results-in-sleep-research https://www.affectablesleep.com/blog/beyond-cherry-picking-m...)

pedalpete 1y ago

There is a growing body of research showing that increasing slow-wave activity during sleep can improve outcomes, including sleep quality[1], memory, and correlations with amyloid response[2]. 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 https://affectablesleep.com . Mild-to-moderate Alzheimer’s changes in sleep https://doi.org/10.1016/j.jagp.2024.07.002 https://doi.org/10.1016/j.jagp.2024.07.002 Slow-wave activity, memory, and amyloid response https://doi.org/10.1093/ageing/afad228 https://doi.org/10.1093/ageing/afad228

DaveZale 1y ago
yes, poor sleep quality leads to bad days, bad days lead to more bad sleep, it is a downward spiral and may impact many of us in our prime years, too. 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.
- pedalpete 1y ago
  Thanks. A researcher we work with has postulated that build-up of metabolic waste (amyloid and tau, among others) directly impairs the glymphatic system, leading to more build-up. A viscous cycle. 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.
  - DaveZale 1y ago
    that's a cute Freudian slip (or deliberate joke) - viscous cycle - sure, amyloid and tau are probably very viscous when you poke at them with the laboratory utensil of your choice. And accumulation of them is like a viscious cycle of plaque accumulation and even worse clearance. It seems exponetial

mcswell 1y ago

I am not understanding this: "It can’t directly predict who will develop Alzheimer’s, but it does identify who could be at a higher risk." I get the part that it can't "directly predict", but what does it mean to "identify who could be at a higher risk"? How was "higher risk" independently diagnosed in the study in order to show a correlation between higher risk according to this test, and higher risk according to some other test?

dmbche 1y ago
"Patients with amnestic MCI—who have memory loss as their main symptom and are more likely to develop Alzheimer’s compared to people with non-amnestic MCI—had lower responses to the test, reports the Guardian’s Ian Sample. It can’t directly predict who will develop Alzheimer’s, but it does identify who could be at a higher risk." 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)

kingofmen 1y ago

> may identify > linked to Really putting their necks on the chopping block and making with the bold opinions, here.

sujit1779 1y ago

[dead]

nextrastapasta 1y ago

[dead]