Blockbuster results from Cognito Tx (40Hz sound, light)

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Family Tree Guy
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Blockbuster results from Cognito Tx (40Hz sound, light)

Post by Family Tree Guy »

APOE4 friends, if you have not yet seen it, the news from the PD / AD conference week is quite impressive:

https://www.businesswire.com/news/home/ ... 005355/en/

Cognito Therapeutics Ph2 study with their device to apply 40Hz sounds and lights has just demonstrated 83-84% decrease in cognitive decline and 61% decrease in brain atrophy vs sham placebo.

For context, remember the very best anti-amyloid drugs (Aducanumab, Biogen and Donanemab , Lilly) only reduced the rate of decline ~22% (Biogen) and ~30% (Lilly)

The mechanism of action related to brainwave entrainment, essentially 'syncing' the brainwaves to the externally applied frequency. this seems to get the microglial system / autophagy process on track. No side effects reported, unlike the anti-amyloid drugs which lead to ~30% brain swelling in E4 carriers.
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Re: Blockbuster results from Cognito Tx (40Hz sound, light)

Post by NF52 »

Family Tree Guy wrote:APOE4 friends, if you have not yet seen it, the news from the PD / AD conference week is quite impressive:

https://www.businesswire.com/news/home/ ... 005355/en/

Cognito Therapeutics Ph2 study with their device to apply 40Hz sounds and lights has just demonstrated 83-84% decrease in cognitive decline and 61% decrease in brain atrophy vs sham placebo.

For context, remember the very best anti-amyloid drugs (Aducanumab, Biogen and Donanemab , Lilly) only reduced the rate of decline ~22% (Biogen) and ~30% (Lilly)... No side effects reported, unlike the anti-amyloid drugs which lead to ~30% brain swelling in E4 carriers.
Thanks for posting this, FamilyTreeGuy.

No question the results in this Phase 2 trial are promising. By design, Phase 2 trials are small, since they study both safety (serious adverse events) and efficacy (meeting pre-specified primary and secondary endpoints of statistical significance). This one had 20 participants assigned to the placebo arm and 31 assigned to the intervention.

The devil is in the details, which we'll have to wait to see when results are published in a peer-reviewed journal and what happens in a larger Phase 3 trial. All of the drugs that failed in Stage 3 trials with hundreds or thousand of participants looked very promising in Phase 2.

I'm curious about the wide range of participants, from "Mild Cognitive Impairment (MCI), due to AD" (which usually means confirmed by a amyloid PET scan) to moderate AD. Those are widely different groups and would require careful balancing of the placebo and treatment assignment arms.

The company also didn't report on what the FDA would be looking for: the pre-specified Primary Outcome Measure. Here's what the company said would be the
Primary Outcome Measures :
Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog) [ Time Frame: Quarterly over 6 months ]
A widely accepted, validated measure of cognitive function in Alzheimer's Disease consisting of 14 questions that results in a score ranging from 0 to 90 with higher scores representing greater cognitive impairment
https://clinicaltrials.gov/ct2/show/NCT03556280

For background, here's what Wikipedia says about the ADAS-COG.
The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is ...one of the most widely used cognitive scales in clinical trials and is considered to be the “gold standard” for assessing antidementia treatments....
The ADAS-Cog consist of 11 questions:
Word Recall Task....Naming Objects and Fingers....Following Commands....Constructional Praxis....Ideational Praxis....Orientation.....Word Recognition Task....Remembering Test Directions....Spoken Language... Comprehension...Word-Finding Difficulty
https://en.wikipedia.org/wiki/ADAS-Cog

Cognito Therapeutics reported instead on change in MMSE scores and the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ACDS-ADL). These are some of the skills asked of the Study Partner (usually a spouse or adult child) about for the preceding 4 weeks, with the needed level of supervision. Scores range from "3" (no supervision needed) "2" (some supervision) to "1" (physical help needed): Writing down "anything", finding personal belongings, choosing clothes, using an appliance (ex. toaster over, microwave, washer), using a telephone, doing laundry, cleaning a room, balancing a checkbook, making a snack or meal, talking about current events, traveling independently, reading for more than 5 minutes at a time. ADCS - ACTIVITIES OF DAILY LIVING (ADL) INVENTORY With only 20 people in the placebo group and some ranging from MCI to moderate AD, I wonder if the changes noted, which could come from losing 1 or 2 points in slight changes on answers to two or three skills. (Does "some supervision" in laundry mean telling a spouse which items go in cold water, or is it telling them how to get to a familiar location when driving?)

Here's what the FDA recommended for trials with MCI back in about 2013:
For MCI trials, the FDA recommended a combined cognitive and IADL measure such as the Clinical Dementia Rating (CDR) scale or two separate measures, one for cognition and the other for IADL..[/quote Measuring instrumental activities of daily living in non-demented elderly: a comparison of the new performance-based Harvard Automated Phone Task with other functional assessments

I would love to see a device like this be as effective as this study suggests; so let's hope they have some angel investors the NIH/NIA ready to bankroll a far bigger study!
4/4 and still an optimist!
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Re: Blockbuster results from Cognito Tx (40Hz sound, light)

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No question, it is just a small Ph2 study. The company (a spinout from MIT) will report more on their data during a presentation Friday morning at the PD / AD conference. I love following the cutting edge science where people are trying entirely new approaches, this is an example of something new. And no matter the argument over anti-amyloid drugs being FDA approvable or not, I simply cannot get excited by their minimal efficacy (slowing decline 20-30% at best).

Keep an eye on this Cognito Therapeutics. And by the way, you can actually try it yourself-- there are plenty of free apps and downloads of 40Hz / gamma frequency sounds. Cognito syncs light with sound, but the sound alone is easy to try. My own experience is that it has a dramatic influence on my sleep-- inducing extremely vivid dreams and deep sleep. (note that 40Hz is the frequency associated with REM sleep when the microglial system is extremely active, so to some degree the concept is to train your brain to sleep deeper)
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Re: Blockbuster results from Cognito Tx (40Hz sound, light)

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Family Tree Guy wrote:there are plenty of free apps and downloads of 40Hz / gamma frequency sounds.....it has a dramatic influence on my sleep-- inducing extremely vivid dreams and deep sleep.
Interesting. My own impression was that 40Hz was stimulating and not at all relaxing. I have an app called Mindroid and 40Hz/Gamma is associated with productivity. Sleep and relaxation are all much lower frequencies.

What time of day do you use the Gamma/40Hz program?
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Re: Blockbuster results from Cognito Tx (40Hz sound, light)

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NewRon wrote:
Family Tree Guy wrote:there are plenty of free apps and downloads of 40Hz / gamma frequency sounds.....it has a dramatic influence on my sleep-- inducing extremely vivid dreams and deep sleep.
Interesting. My own impression was that 40Hz was stimulating and not at all relaxing. I have an app called Mindroid and 40Hz/Gamma is associated with productivity. Sleep and relaxation are all much lower frequencies.

What time of day do you use the Gamma/40Hz program?
To clarify, the 40Hz is not sleep promoting or 'inducing'. I listen to 40Hz for an hour at some point in the mid afternoon, typically while I am doing something else like catching up on emails or reading.

If you want help getting ready for sleep in the evening, then I would recommend what are called delta waves, which are much much slower. However, the 40Hz is 'isochronic' (same frequency in each ear). If you want to relax before sleep with delta waves, most music or apps will achieve that with 'binaural' beats of some type. With that, each ear 'hears' a slightly different frequency (say 400Hz and 405Hz). Then the brain perceives this as 5Hz and your brainwaves sync to this (the phenomenon is called 'brainwave entrainment').

Try it for yourself some time-- listen to 1 hour of 40Hz for a few days while doing something else. Then see how you feel when you wake up-- I bet you will notice that you have had intensely more vivid dreams.
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Re: Blockbuster results from Cognito Tx (40Hz sound, light)

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You know what might be worth considering? apoe4 forum members could do their own clinical trial for gamma frequency or perhaps homotaurine! Roughly, we could select some sort of online test and then members could post their treatment schedule and results! Cognito has only reported on about ~100 patients so far. Why not help?

It is somewhat difficult to imagine that given the enormity of the AD challenge that there is no obvious virtual test that we could grab off the shelf, though perhaps we can work through together an acceptable test (possibly from pebl). There might even be grown ups out there that could help us! Yeah, grown ups! This might truly help in the development of some of these treatments and in turn help out members of our forum.

Comments please!
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Re: Blockbuster results from Cognito Tx (40Hz sound, light)

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Family Tree Guy wrote: Try it for yourself some time-- listen to 1 hour of 40Hz for a few days while doing something else. Then see how you feel when you wake up-- I bet you will notice that you have had intensely more vivid dreams.
I am going to try this now will report back here.
Last edited by floramaria on Fri Mar 12, 2021 12:05 pm, edited 1 time in total.
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Re: Blockbuster results from Cognito Tx (40Hz sound, light)

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@floramaria- happy dreams!
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Re: Blockbuster results from Cognito Tx (40Hz sound, light)

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J11 wrote:You know what might be worth considering? apoe4 forum members could do their own clinical trial for gamma frequency or perhaps homotaurine! Roughly, we could select some sort of online test and then members could post their treatment schedule and results! Cognito has only reported on about ~100 patients so far. Why not help?

It is somewhat difficult to imagine that given the enormity of the AD challenge that there is no obvious virtual test that we could grab off the shelf, though perhaps we can work through together an acceptable test (possibly from pebl). There might even be grown ups out there that could help us! Yeah, grown ups! This might truly help in the development of some of these treatments and in turn help out members of our forum.

Comments please!
I'm interested in an apoe4 clinical trial! Though I don't have any testing expertise to contribute.

Thanks for all the information you've provided about drug and other treatment trials, J11.
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Re: Blockbuster results from Cognito Tx (40Hz sound, light)

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J11 wrote:You know what might be worth considering? apoe4 forum members could do their own clinical trial for gamma frequency or perhaps homotaurine!...Comments please!
DebbieG wrote: I'm interested in an apoe4 clinical trial! Though I don't have any testing expertise to contribute.

Thanks for all the information you've provided about drug and other treatment trials, J11.
Hi DebbieG,

Thank you (and J11) for your interest in ApoE4 clinical trials! You might be interested in checking out our new Wiki on
ApoE ε4 Alzheimer's Research: What's New and How YOU Can Accelerate Research

Many clinical trials, and even online registries looking to study people with digital apps, struggle to recruit enough people. The wiki also has links to some topics in the forum on ApoE 4-related research and current evidence of ApoE 4-effective non-drug interventions.

As for those tests and assessments, that's a crucial issue these days, with many sessions in recent conferences by the Clinical Trials in Alzheimer's Trials (CTAD) and Alzheimer's Association focused on fascinating topics. One showed evidence that the "practice effect"--a common observation that more people improve on tests. for the first three sessions, then either stay stable or decline over time--may give a true "baseline" to measure changes. Another compared assessments of independent living skills and noted that some skills on common assessments change only later in AD, and are not useful for prevention trials. Most trial use composite scores of multiple cognitive areas, recognizing that a slight dip in the ability to remember numbers, for example, may be insignificant if every other cognitive ability is stable.

When we as individuals collect information, it's an observational study--and the kind of work that COVID "long-haulers" have done that resulted in funding from the NIH for large-scale studies of the scope of that issue. So pooling data on gamma could be helpful. As for homotaurine, I'm eager to see results of this tramiprosate-modified drug Biomarker Effects of ALZ-801 in APOE4 Carriers With Early Alzheimer's Disease and the projected ALZ-801 prevention study of ApoE 4/4's in 2022 (or maybe 2023).
4/4 and still an optimist!
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