Answers to important questions:
Question: What is gender therapy and how does it work?
A: GENUS (Gamma Synchronization through Sensory Stimuli) delivers synchronized light and sound at 40Hz to promote healthy brain wave activity associated with memory and cognition.
Q: What improvements have been seen in Alzheimer’s patients after long-term use?
A: In participants with late-onset Alzheimer’s disease, slower cognitive decline, improved circadian rhythms, and lower tau protein levels were observed over two years of treatment.
Q: Why did early-onset Alzheimer’s patients respond differently?
A: Researchers believe that early-onset Alzheimer’s disease represents a broader pathology of the brain, making it less responsive to gamma radiation stimulation.
Summary: A long-term study suggests that daily light and sound stimulation at 40 Hz can reduce cognitive decline in people with late-onset Alzheimer’s disease. After two years of treatment, participants maintained better cognitive performance than the general population of Alzheimer’s patients and showed lower levels of the protein tau, an important biomarker of the disease.
The non-invasive therapy, known as GENUS, works by using light and sound to synchronize brain activity to a 40 Hz gamma rhythm. Although patients with early-onset Alzheimer’s had less benefit, the researchers say the results highlight the potential of a safe, home-based treatment to slow the progression of the disease.
Key data
- Lasting benefits: Participants with late-onset Alzheimer’s maintained higher cognitive scores and improved sleep patterns for two years.
- Biomarker reduction: In two participants, a significant reduction in plasma tau levels was observed, which is associated with Alzheimer’s disease.
- Safe and non-invasive: GENUS 40 Hz Light and Sound Therapy was well tolerated and found to be suitable for daily use at home.
Source: MIT Pecor Institute
A new research paper describes the results of five volunteers who continued to receive 40 Hz light and sound stimulation for nearly two years after participating in an early-stage MIT clinical trial of a potential treatment for Alzheimer’s disease.
The results showed that in three participants with late-onset Alzheimer’s disease, multiple cognitive levels were significantly higher than in comparable Alzheimer’s patients in a national database.
In addition, in two volunteers with late-onset disease who donated plasma, levels of tau protein, a biomarker for Alzheimer’s disease, were significantly reduced.
Three of the volunteers who experienced these benefits were women. The other two participants, both men who had an early form of the disease, showed no significant benefit after two years.
Although the dataset is small, it represents the longest trial to date of a safe, noninvasive treatment procedure (called GENUS, for gamma entrainment using sensory stimuli). It is also being evaluated in a nationwide clinical trial led by Cognitive Therapeutics, an MIT subsidiary.
This pilot study, detailed in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, evaluated the long-term effects of daily $40 \text{ Hz}$ GENUS multimodal therapy in patients with mild Alzheimer’s disease (AD). The authors concluded that using daily audiovisual stimulation at a frequency of $40 \text{ Hz}$ for two years is both safe and feasible.
Furthermore, the study provided evidence that this daily stimulation can slow the progression of cognitive decline and biological markers of the disease. The authors noted that this effect was particularly promising and observable in patients suffering from late-onset Alzheimer’s disease.
Diane Chan, a former researcher at the Picower Institute for Learning and Memory and a neurologist at Massachusetts General Hospital, is the lead author and corresponding co-author of the study. Professor Li-Huei Tsai, director of the Picower Institute and the MIT Brain Aging Initiative, is the lead author and corresponding co-author of the study.
“Open Label” Expansion
In 2020, MIT enrolled 15 volunteers with mild Alzheimer’s disease in an early-stage study to examine whether one hour of 40 Hz light and sound stimulation per day, delivered through an LED panel and speaker in their home, could provide clinically significant benefits.
Several studies in mice have shown that sensory stimulation increases the strength and coherence of 40 Hz gamma waves in the brain, preserves neurons and their neural connections, reduces the amount of proteins associated with Alzheimer’s disease, such as amyloid and tau proteins, and improves learning and memory. Several independent groups have obtained similar results over the years.
The MIT study, although paused due to the Covid-19 pandemic, showed significant benefits after just three months. The new study examined the results of five volunteers who used their stimulation devices openly for two years.
These volunteers returned to MIT 30 months after their initial participation for a series of tests. Because four participants had started the original study as a control group (i.e., they did not initially receive 40 Hz stimulation), their participation in the open-label study was six to nine months shorter than the 30-month period.
Tests conducted at 0, 3, and 30 months after enrollment included measurements of brain wave responses to stimulation, MRIs of brain volume, measurements of sleep quality, and a battery of five standardized cognitive and behavioral tests.
Two participants donated blood samples. To compare them with untreated controls, the researchers examined three national databases of Alzheimer’s patients and matched thousands of them based on criteria such as age, sex, baseline cognitive scores, and reassessments at similar intervals over a 30-month period.
Results and possibilities
In three volunteers with late-onset Alzheimer’s disease, improvements or slow declines were observed on most cognitive tests. In three of these, there were significant positive differences compared to the control group.
These volunteers also showed stronger brain wave responses to stimulation and improvements in circadian rhythm measurements after 30 months. In two volunteers with late-onset Alzheimer’s disease who provided blood samples, significant reductions in phosphorylated tau protein were observed (by 47% in one and 19.4% in the other) in a test recently approved by the FDA as the first plasma biomarker for diagnosing Alzheimer’s disease.
The authors noted that one of the most compelling findings was the significant reduction of plasma pTau217—a biomarker highly correlated with Alzheimer’s disease (AD) pathology—observed in the two late-onset AD patients for whom blood samples were available.
They concluded that these specific results strongly suggest $GENUS$ therapy may have a direct biological impact on AD pathology, thus making a strong case for further, more detailed mechanistic investigation in larger, randomized clinical trials.
Although initial research results showed that brain volume was preserved after 3 months in those receiving 40 Hz stimulation, this was no longer significant after 30 months.
Two male volunteers with early-stage disease showed no significant improvement in cognitive test scores. Specifically, these patients had significantly reduced brain wave responses to stimuli.
Although the sample size is small, the authors hypothesize that the difference between the two groups of patients is due to differences in disease onset and not to differences in gender.
“GENUS may be less effective in patients with early-onset AD, possibly due to broader pathological differences compared with late-onset AD, which may contribute to differential response,” the authors wrote. “Future research should investigate predictors of treatment response, such as genetic and pathological markers.”
The research team is currently investigating whether GENUS could have a preventive effect when used before the onset of the disease. The new clinical trial is recruiting participants over the age of 55 with normal memory who have or have had Alzheimer’s disease, including those with early onset.
In addition to Chan and Tsai, the article’s co-authors are Gabrielle DeWaque, Brennan L. Jackson, Ho Jun-sik, Noah P. Millman, Erin Kitchener, Vanessa S. Fernandez-Avolos, M.J. Quay, Kenji Aoki, Erica Ruiz, Andrew Baker, Monica Zheng, Remens, Romains, Romains, Flynns, Geino Hammerschlag, Steven Arnold, Pia Kivisäkk, Michael Brickhouse, Alexandra Touroutoglou, Emery N. Brown, Edward S. Boyden, Bradford C. Dickerson, and Elizabeth B. Klerman.
Funding: Research funding was provided by the Freedom Together Foundation, the Robert A. and Renee E. Belfer Family Foundation, the Eleanor Schwartz Charitable Foundation, the Dolby Family, Che King Liu, Amy Wong and Calvin Chen, Kathleen and Miguel Octavio, the Family Foundation, the Halifax Foundation, DeGroff VM, Chijen Everdo, LaBrie, DeGroff, and E.D. Gary Hua and Lee Chen, the Ko Han Family, Lester Jemplson, David B. Ames, Joseph P. Desabato and Nancy E. Sakamoto, Donald A. and Glinda G. Mattis, the Carol and Jane Ludwig Family Foundation, Alex Ho and Ann Russell, Elizabeth K. Russell, K. Russell, Mary D. Ko and James Warr Foundation, Haubert Warr Foundation, Elizabeth Ko H. Hardner Foundation.
About this Alzheimer’s disease and neurotech research news
Author: David Orenstein
Source: Picower Institute at MIT
Contact: David Orenstein – Picower Institute at MIT
Image: The image is credited to StackZone Neuro
Original Research: Open access.
“Gamma sensory stimulation in mild Alzheimer’s dementia: an open-label extension study” by Diane Chan et al. Alzheimer’s & Dementia
Abstract
Gamma sensory stimulation in mild Alzheimer’s dementia: an open extension study
Introduction
We evaluated the long-term effects of daily audiovisual stimulation at 40 Hz (gamma frequency) on cognition and biomarkers in five patients with mild Alzheimer’s disease (AD).
Methods
For over two years, patients received stimulation for one hour daily. Electroencephalography (EEG) was used to assess neuronal synchronization; magnetic resonance imaging (MRI) to measure brain volume; actigraphy to monitor activity patterns; neuropsychological tests to assess cognition; and the S-PLEX test to measure plasma pTau217.
Results
No adverse events were reported during the study period. Three female patients with late-onset Alzheimer’s disease (LAAD) maintained robust electroencephalographic coherence and showed less decline in scores on the Mini-Mental State Examination (MMSE), Clinical Deterioration Scale (CDR), and Functional Assessment Scale (FAS), compared with controls from the Alzheimer’s Center National Discordant Alzheimer’s Disease Neuroimaging Initiative (ADNI), and the Longitudinal Study of Early-Onset Alzheimer’s Disease (LEADS). Plasma samples were available from only two of the five participants—both with LAAD—and both showed a 47% and 19% reduction in pTau217.
Discussion
These results suggest that prolonged audiovisual stimulation at 40 Hz is safe and feasible and may offer cognitive and biomarker benefits in some individuals with mild AD. Therefore, further research is needed.
Information about clinical trial registration
ClinicalTrials.gov (NCT04055376).
