An Hour of Light and Sound a Day Might Keep Alzheimer’s at Bay

[Alvin]

Bathing patients in flashing light and pulsing sounds both tuned to a frequency of 40 hertz might reverse key signs of Alzheimer’s in the brain, according to a paper published in Cell on Thursday. “I think it’s an absolutely fascinating paper to be honest,” says Macauley, who was not involved in this work. “It’s a very provocative idea. It’s noninvasive and easy and low cost, potentially, so if it were to come to fruition in humans—that’s fabulous.”

Still, all this is a big if, Macauley acknowledges. The work was done in mice with genetic alterations that doomed them to develop key symptoms and pathology of Alzheimer’s disease. One batch of mice formed neurofibrillary tangles inside their neurons—dysfunctional knots of a protein called tau that can lead to the cell’s death. Another batch of the mice developed amyloid beta plaques—sticky heaps of protein that dam the flow of communication between neurons. All the mice also had a third hallmark of the disease—irregular brain activity in the gamma range of brain waves that oscillate between 30 and 100 times a second

https://www.scientificamerican.com/...and-sound-a-day-might-keep-alzheimers-at-bay/

 

[roller*]

40 hz is called "Gamma Band" (Neural Stimulation)

Importantly, the external supply of the stimulus, delivered via the retina, optic nerve and subsequent pathways was translated as an increase in gamma activity in the visual cortex.

Also, of interest was the discovery that GABAergic neurons are likely involved in the process, with the use of a GABA antagonist nullifying the neural and microglial mediate effects.

"Gamma Band Neural Stimulation in Humans and the Promise of a New Modality to Prevent and Treat Alzheimer’s Disease"

"Finally, AD patients may feature a reduction in the power of gamma activity [36, 37]. Therefore, modifying gamma activity for patients with AD may support improved cognitive function.
Significantly, these effects were seen only with a 40 Hz stimulus, and not with 20 Hz, 80 Hz or random frequencies.

Further, this reduction in gamma activity was observed before the accumulation of amyloid plaque or evidence of cognitive impairment ((((in hippocampus))))
It was further shown that increasing gamma activity in the CA1 region of the hippocampus, by stimulation of optogenetically modified interneurons using blue light at 40 Hz, reduced Aβ levels by approximately 50% and was mediated by both neural and microglia mechanisms.

Gamma activity is electrical activity which occurs at frequencies ranging from 30–100 Hz [18]; with the 40 Hz gamma activity of most interest

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130417/



5 - 9 Hz - brown note

The brown note is a hypothetical infrasonic frequency that would cause humans to lose control of their bowels due to resonance. Attempts to demonstrate the existence of a "brown note" using sound waves transmitted through air have failed.

The name is a metonym for the common color of human feces. Frequencies supposedly involved are between 5 and 9 Hz, which is below the lower frequency limit of human hearing. High power sound waves below 20 Hz are felt in the body, not heard by the ear as sound

30 hz - parkinson

In 2009, researchers led by Lauren K. King of the Sun Life Financial Movement Disorders Research and Rehabilitation Centre at Wilfrid Laurier University, in Waterloo, Ontario, found that short-term use of vibroacoustic therapy with Parkinson's disease patients led to improvements in symptoms, including less rigidity and better walking speed with bigger steps and reduced tremors (NeuroRehabilitation, December, 2009). In that study, the scientists exposed 40 Parkinson's disease patients to low-frequency 30-hertz vibration for one minute, followed by a one-minute break.

https://www.apa.org/monitor/2013/11/music
https://www.ncbi.nlm.nih.gov/pubmed/20037223



40 hz - alzheimers

"Since the rhythmic pulses of music can drive and stabilize this disorientation, we believe that low-frequency sound might help with these conditions," Bartel says. He is leading a study using vibroacoustic therapy with patients with mild Alzheimer's disease. The hope is that using the therapy to restore normal communication among brain regions may allow for greater memory retrieval, he says.

"We've already seen glimmers of hope in a case study with a patient who had just been diagnosed with the disorder," Bartel says. "After stimulating her with 40-hertz sound for 30 minutes three times a week for four weeks, she could recall the names of her grandchildren more easily, and her husband reported good improvement in her condition."

https://www.apa.org/monitor/2013/11/music
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141741/



432 Hz - frequency of the universe

432 Hz. The magic number everybody is talking about. It is said to be the natural frequency of the universe, to have cosmic healing powers and to attract masses of audience to our music. Just by tuning our music less than a semitone below our standard A=440Hz we are promised direct access to the universe's hidden treasures.

https://ask.audio/articles/music-theory-432-hz-tuning-separating-fact-from-fiction

 

[roller*]

... external stimuli ...vestibular system ... ?
does this frequency "loss" have something to do with unexplained hearing loss ?

after googling it seems a stupid question: would it be possible to display the hz-frequencies in youtube-music ?

 

[roller*]

Accelerated Learning | Gamma Waves for Focus, Concentration, Memory | Monaural Beats | Focus Music
40 Hz Gamma Monaural Beats



40hz per second flashing Alzheimer's disease light therapy

 

[roller*]

to find out if you can hear 40 hz at all ...

... perhaps some AD patients may not hear much at those low frequencies, and thats why they use flickering LIGHT-40hz to activate it?

wondering, if 40hz-light-flicker-therapy may restore a neurosenso-hearing-fail at 40hz... ?

on youtube they have a range of test tone videos https://www.youtube.com/playlist?list=PLzFvCAfIq7a2SIBfDhpCytfJ4RHVb_KLY

 

[Wonko]

Anybody got a device capable of playing back 40Hz video as intended? My Tv or monitor can't, they weren't designed to - 50Hz to 120Hz is what they were designed for, with the odd trip down to 24Hz in the case of the TV - but 40Hz? - what is the point of having that on youtube?

 

[roller*]

@Wonko you think, 40hz lights on youtube are not played on the laptop with 40hz ?

im searching for a light bulb with this flicker frequency ... "light therapy", possibly

 

[Wonko]

no idea, @Wonko
you think, 40hz lights on youtube are not working ?

im searching for a light bulb with this flicker frequency, but cant find anything so far

How could a 50Hz device accurately display 40Hz without generating an interference pattern of some sort? Even if that's suppressed the result wouldn't be a 40Hz flicker but some hybrid.

I may or course be wrong, but several years ago I spent a fair amount of time, effort and money trying to get around a similar problem, using conventional equipment, that was causing rendering/playback issues.

Just coz the source is fine, and the playback device can handle it, doesn't mean the renderer can (in this case a monitor/TV).

ETA - 40Hz sound is incredibly annoying, and the video, yes it has interference when played back on my 50Hz TV, or even at 60Hz - it might be okay at 80Hz but I can't seem to do that, 79Hz is the closest to 80Hz I can get.

I now have a mild headache, from under 20 seconds of exposure to the video. Not complaining, just something for others to be aware of.

 

[roller*]

sorry to hear @Wonko

i dont know what it sounds or may cause since i dont hear anything at 40hz

im "moderate neurosensory hearing loss"

 

[Wonko]

sorry to hear @Wonko

i dont know what it sounds or may cause since i dont hear anything at 40hz

im "moderate neurosensory hearing loss"

It sounds a bit like a swarm of insects if you've ever heard one of them, possibly on a nature program or horror film. Just deeper and quieter. No idea why it's annoying but it was.

 

[roller*]

It sounds a bit like a swarm of insects if you've ever heard one of them, possibly on a nature program or horror film. Just deeper and quieter. No idea why it's annoying but it was.

sounds like my "tinnitus"-thing...

there is another interesting article, how they found out about AD-frequency (2018)
https://www.nature.com/articles/d41586-018-02391-6

but .. the engineered AD mice are not perfect matches to human AD (though, it seems the frequencies indeed help in humans)
and "Gamma oscillations are the type most likely to induce seizures in people with photosensitive epilepsy"
and amiloid is produced for protection i understand, so it may make sense that its there (the lesser evil, sort of)

 

[Forbin]

Bathing patients in flashing light and pulsing sounds both tuned to a frequency of 40 hertz might reverse key signs of Alzheimer’s in the brain, according to a paper published in Cell on Thursday.

When I first read this, I took "bathing" literally.

 

[akrasia]

I’ve been following Cognito Therapeutics for a couple of years, waiting to hear more about the progress of its Gamma 40 hz study on human subjects with Alzheimer’s. Well, it seems they have appointed a new CEO, which portends good developments are on the horizon.

(Cognito Therapeutics was set up in the wake of the striking results of the mouse studies that showed reductions in beta amyloid, tau, and stimulation of the microglia in the brain. Its primary purpose is to bring to market a sound /light device that can reliably deliver the 40hz gamma frequency to human ears and eyes. The study organized by Li Huei Tsai started last summer and will last until summer 2021)

https://www.businesswire.com/news/home/20201209005339/en/Cognito-Therapeutics-
Appoints-Industry-Pioneer-Brent-Vaughan-as-Chief-Executive-Officer


This summer of 2020 article gives an extended overview of the state of play in 40hz light/sound treatments:

https://www.pnas.org/content/117/31/18142

The first link below requires only a registration. While some of it seemed opaque to this humanities brain, it’s aimed at a general audience, and was very lucid and compelling, so in contrast to the turbid muck we have to so often engage. It’s Li Huei Tsai speaking and lasts about an hour.

https://www.technologynetworks.com/...rain-waves-to-fight-alzheimers-disease-329617

For a much shorter version there’s a 4 minute film clip on the NIH site.
https://www.nia.nih.gov/news/noninv...ces-alzheimers-pathology-improves-memory-mice

Li Huei Tsai is quoted in the PNAS article as already considering autism, schizophrenia, as well as other neuro degenerative diseases as potential targets for studies. If this holds up it is a remarkable moment for medicine.

 

[akrasia]

 

[akrasia]

https://www.businesswire.com/news/h...mer’s-Disease-at-2021-ADPD-Virtual-Conference


Cognito Therapeutics to Announce New Clinical Data Evaluating Gamma Frequency Neuromodulation to Treat Alzheimer’s Disease at 2021 AD/PD Virtual Conference
March 02, 2021 08:00 AM Eastern Standard Time


CAMBRIDGE, Mass.--(BUSINESS WIRE)--Cognito Therapeutics, a clinical-stage company leading the development of a new class of disease-modifying digital therapeutics to treat neurodegenerative disorders, announced today it will present for the first time, new clinical data for its digital therapeutic utilizing gamma frequency neuromodulation in Alzheimer’s Disease, at the 15th International Conference on Alzheimer's and Parkinson's Diseases (AD/PD), held virtually March 9-14, 2021.

Details of the symposium panel are below:

Symposium title: Gamma sensory stimulation, a novel AD therapeutic intervention: initial safety, efficacy and biomarker changes from two prospective clinical studies

Date/Time:

Friday, March 12, 10:00 – 11:00 am ET, followed by Live Q&A

Moderator:

Dr. Li-Huei Tsai, neuroscientist and the Director of the Picower Institute for Learning and Memory in the Department of Brain and Cognitive Sciences at MIT

Panelists:

Dr. James Lah, Principal Investigator of the Flicker study, and Director of the Cognitive Neurology Program, Emory University

Dr. Tom Megerian, Chief Medical Officer, Cognito Therapeutics

Dr. Suzanne Hendrix, CEO, Pentara Corporation

A replay of the symposium panel will be posted on Cognito’s website at www.cognitotx.com.

 

[Wonko]

I've just re-read this thread and come to the conclusion that the hypothesis makes absolutely no sense, at least to me.

What is the proposed mechanism? Why 40 hz and not 39.996734hz?

Given that processing in the visual and auditory systems does not run at the same speed, or with the same 'integrity' (most of what we see, and hear, is entirely fictional, a best guess, to cut processing time and load - or so I am told) why use the same frequency for both input methods?

and bits about the 'frequency of the universe' - erm....sounds like something that might not be....100% accurate in the context of anything else but the alleged frequency fo the universe (and has anyone checked that number, everywhere (including places with no matter), at every speed?).

 

[Kitty]

and bits about the 'frequency of the universe' - erm....sounds like something that might not be....100% accurate in the context of anything else but the alleged frequency fo the universe(and has anyone checked that number, everywhere (including places with no matter), at every speed?)

Yep.

It's 42.

 

[akrasia]

Li Huei Tsai, who runs a lab at MIT, inspired by 2 of her graduate students, decided to see whether the robustness of gamma waves in the brain showing alzheimers pathology,could be increased by exposure to light. To do this, she enlisted the help of Ed Boyden, also of MIT and one of the founders of a method of cellular engineering called Optogenesis, a technique in which lights implanted into the brain are used to turn specially tagged brain cells off and on.
.

The first target was the hippocampus of mice bred to overproduce amyloid beta.Tsai and her team used a fiber optic cable to pulse the light. They found that gamma waves at 40 Hz could significantly reduce levels of the peptide. When the scientists studied these animals’ brains further, they found evidence that immune cells called microglia had cleared the peptide. The microglia show very striking morphological transformation, their gene expression profile changes, and they appear to have more amyloid in their cell bodies.



It is well known that gamma waves are disrupted, have low coherence, in AD as well as other degenerative neuropathologies. The 40 Hz frequency stems from the observation that brains of Alzheimer’s patients suffer early on from a lack of gamma, moments of gentle, constant brain waves that activate neuron activity. Its most common frequency is around 40 Hz—making that number the perfect target. The idea behind the study was to influence gamma oscillations, a measure of rhythmic activity among neurons that ranges from 25 to 80 hertz. Tsai, and her lab tried pulses from 20 to 80 Hz and found that 40 was the sweet spot. Somehow — neither Dr. Tsai nor outside experts are quite sure how — 40 hertz produces a gamma-wave oscillation that appears to increase activation of cells called microglia, which perform trash-clearing and immune-regulating functions. The microglia became more efficient at chewing up the amyloid protein that forms toxic plaques in Alzheimer’s.


The optogenetics phase of the study established a relationship between gamma and the brain’s immune cells, but obviously was not practical for human treatment purposes. So they moved on to led’s mounted to a strip and exposed the mice, who were now bred to express alzheimers in the visual cortex, and observed similar results to the optogenetic phase of the study.
While this work, published in Nature, represented a breakthrough in understanding the Alzheimer’s disease process, Tsai et al. realized that the effects of pulsed light did not extend much beyond the visual cortex, not a common site for disease pathology

So, they tried 40hz audio.

40 hz. audio treatment led to a dramatic shift. affecting glia and blood vessels in the auditory cortex and hippocampus. Microglia appeared enlarged, with shorter, more branched processes, and they ate up more plaques, while astrocytes became up to 20 percent more reactive. At the same time, blood vessels grew wider, some doubling their diameter (see image below)

*Vasodilation.*/After a week of auditory stimulation , blood vessels (green) expand relative to their normal diameter compared with unstimulated mice (top). [Image courtesy of Martorell et al., 2019.]

But when light was added the results became synergistic:
The combined treatment led to fewer A-beta plaques across a big stretch of the brain, including the hippocampus and the prefrontal cortex, an area important for complex thinking. Microglia seemed to pile up on each other, all congregated around the amyloid plaques in what Tsai called a feeding frenzy.



The gamma became more robust, more globally disseminated, particularly in the areas of the brain where AD is at it most destructive., the hippocampus and the frontal precortex.

Effects they had observed before using only audio, were amplified: memory, new learning, lowered frustration, and other signs of improved cognition.

There is a tragic dimension to the pursuit of a treatment for AD: no matter how promising results in mice have been, 99.6% of treatments end in failure in human trials. The odds are fearsome.

At a recent meeting of the Alzheimer Parkinsons International Li Huei Tsai indicated that the device had met and even surpassed the indices that will send it on to a much enlarged patient sample for phase 3.

[Cognito Therapeutics Announces Positive Phase 2 Results as First Digital Therapeutic to Improve Memory, Cognition, Functional Abilities and Reduce Brain Atrophy in Alzheimer’s Disease | Business Wire](https://www.businesswire.com/news/h...d-Reduce-Brain-Atrophy-in-Alzheimer’s-Disease)
#
* Phase 2 data reported at 2021 AD/PD Conference showed gamma frequency neuromodulation was safe and well tolerated
* Over the 6-month period, patients in the treatment group exhibited a significant 84% slowing of functional decline in ADCS-ADL scores as well as a significant 83% slowing in memory and cognitive decline as measured by MMSE scores compared to placebo/sham
* Patients in the treatment group demonstrated a significant 61% reduction in whole brain atrophy and volumetric loss associated with AD, compared to placebo/sham at 6 months, demonstrating disease modification potential

,Cognito Therapeutics a clinical-stage company developing a new class of disease-modifying digital therapeutics to treat neurodegenerative disorders, announced today positive Phase 2 results showing its digital therapeutic utilizing gamma frequency neuromodulation improved memory, cognition, functional abilities and reduced whole brain atrophy and volumetric loss in patients with mild-to-moderate Alzheimer’s disease (AD).
“Our approach has translated into clinical proof of concept by successfully achieving statistically significant results in AD, with a potential for disease modification due to significant reduction of cerebral atrophy and volumetric loss”
Gamma frequency neuromodulation is a novel digital therapeutic intervention for AD that utilizes EEG-calibrated auditory and visual stimuli to evoke patient-specific neural activity. The mechanism of action has been demonstrated in numerous preclinical studies, where repeated daily exposure to sensory-evoked gamma oscillations resulted in multiple beneficial effects on AD pathophysiology, including reduced production of soluble and insoluble amyloid-beta, microglia-mediated phagocytosis of amyloid plaques, reduced tau-hyperphosphorylation and improved cognitive function.
The Phase 2 OVERTURE study (NCT-03556280) is a multi-center, randomized controlled clinical trial (RCT) evaluating the safety and efficacy of gamma frequency neuromodulation for a 6-month treatment period in a mild-to-moderate AD population. The study enrolled 76 patients aged 50 or older with mild-to-moderate AD (MMSE 14-26, inclusive), randomized to receive either 40 Hz noninvasive audio-visual or sham stimulation one-hour daily at home over the treatment period.
Over the 6-month treatment period, subjects were regularly evaluated for cognitive, functional, and biomarker changes on multiple validated measures. Functional abilities of patients were measured by Alzheimer’s Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale at baseline and every four weeks during the study period. The study also evaluated changes in functional ability and brain volumetric changes in AD patients with mild to moderate cognitive impairment. Brain volumetric changes were assessed by structural magnetic resonance imaging (MRI), taken at baseline and after six months of treatment.
*Results*
Gamma frequency neuromodulation was safe and well tolerated. Over the 6-month period, patients in the treatment group (n=33) exhibited a significant 84% slowing of functional decline in ADCS-ADL scores and a significant 83% slowing in the rate of decline based on the Mini-Mental State Examination (MMSE), compared to patients in the placebo group (n=20). Patients in the treatment group (n=30) also demonstrated a significant 61% reduction in whole brain atrophy and volumetric loss associated with AD, compared to placebo group patients (n=19) at 6 months, indicating a potential disease modifying effect via quantitative MRI analysis.
The Phase 2 study met its primary safety and tolerability endpoints, and selected secondary endpoints were significant. The results demonstrate that active treatment with gamma frequency neuromodulation also led to significant benefits in the ability to perform activities of daily living via the ADCS-ADL and cognition via the MMSE, representing important treatment and management objectives for AD patients.
“We’re excited to announce our Phase 2 data, which demonstrated significant improvements in memory, cognition and reductions in brain atrophy and volumetric loss in AD patients who received treatment with gamma frequency neuromodulation compared to placebo,” said Brent Vaughan, CEO of Cognito Therapeutics. “With our recent FDA Breakthrough Device Designation, we look forward to expediting the clinical development of what has the promise to be the first disease-modifying digital therapeutic in Alzheimer’s disease.”
“Our approach has translated into clinical proof of concept by successfully achieving statistically significant results in AD, with a potential for disease modification due to significant reduction of cerebral atrophy and volumetric loss,” said Dr. Tom Megerian, Chief Medical Officer, Cognito Therapeutics. “In addition to improving functional outcomes, memory and cognition, the 61% reduction in loss of whole brain volume in our Phase 2 study addresses key aspects of AD etiology and disease progression. If these results are replicated in our larger, pivotal trial, this will represent a huge medical breakthrough in Alzheimer’s research.”


————————————————————————————————————————





This is my last post to this thread. PM with any questions I might be of help with.

 

[akrasia]

A couple of new developments:

https://scitechdaily.com/mit-genus-40-hz-vibrations-reduce-alzheimers-disease-symptoms/

“The current study, along with our previous studies using visual or auditory GENUS demonstrates the possibility of using non-invasive sensory stimulation as a novel therapeutic strategy for ameliorating pathology and improving behavioral performance in neurodegenerative diseases,” the authors concluded.

Reference: “Vibrotactile stimulation at gamma frequency mitigates pathology related to neurodegeneration and improves motor function” by Ho-Jun Suk, Nicole Buie, Guojie Xu, Arit Banerjee, Edward S. Boyden and Li-Huei Tsai, 18 May 2023, Frontiers in Aging Neuroscience.



And:

In December 2022, Cognito Therapeutics began enrolling for a Phase 3 trial in 345 people with Alzheimer’s disease. They are to be randomized to either active or sham treatment lasting one hour per day for up to a year, using a sensory stimulation device called GS120. Primary outcomes are change from baseline at 12 months on the ADCS-ADL and change from baseline at 12 months on the combined statistical test (CST) of the ADCS-ADL and MMSE. The trial is being run at 38 sites across the U.S., and is expected to be complete in 2025.

For details on trials of this approach, see clinicaltrials.gov and clinicaltrials.gov.

 

[perchance dreamer]

The Canadian company Vielight has a product for clinical and home use that stimulates the brain with gamma waves. It includes a headset with components placed on different parts of the scalp and also a nasal applicator, which stimulates the underside of the brain.

I think it's important when considering a device like this to have have your brainwaves evaluated at a biofeedback clinic that does neurofeedback. Gamma brain stimulation is not appropriate for all people.

https://www.vielight.com/devices/vielight-neuro-gamma/

https://www.vielight.com/research/