Daily light and sound therapy may slow Alzheimer’s deterioration

Summary: A long-term study found that daily 40 Hz light and sound stimulation may help slow cognitive decline in people with late-onset Alzheimer’s disease. After two years of treatment, participants maintained stronger cognitive performance than typical Alzheimer’s patients and showed reduced levels of tau protein, a key biomarker of the disease.

The non-invasive therapy, known as GENUS, works by synchronizing brain activity at a 40 Hz gamma rhythm through light and sound. While early-onset patients saw fewer benefits, researchers say the results highlight the potential of a safe, at-home intervention to slow the progression of Alzheimer’s.

Key facts

Sustained benefits: Participants with late-onset Alzheimer’s maintained higher cognitive scores and improved sleep patterns for two years. Reduction of biomarkers: two participants showed significant decreases in plasma tau levels, related to Alzheimer’s pathology. Safe and non-invasive: GENUS 40Hz sound and light therapy was well tolerated and feasible for daily use at home.

Source: MIT Picower Institute

A new research paper documents the results of five volunteers who continued to receive 40 Hz light and sound stimulation for approximately two years after participating in an early-stage MIT clinical study of a potential therapy for Alzheimer’s disease.

The results show that for the three participants with late-onset Alzheimer’s disease, several measures of cognition remained significantly higher than those of comparable Alzheimer’s patients in national databases.

Furthermore, in the two late-onset volunteers who donated plasma samples, levels of the protein tau, a biomarker for Alzheimer’s, decreased significantly.

The three volunteers who experienced these benefits were all women. The other two participants, each of whom were men with early forms of the disease, showed no significant benefits after two years.

The data set, although small, represents the longest-term test yet of the safe, non-invasive treatment method (called GENUS, for gamma entrainment using sensory stimuli), which is also being evaluated in a nationwide clinical trial conducted by the MIT spin-out company Cognito Therapeutics.

“This pilot study evaluated the long-term effects of daily 40 Hz multimodal GENUS in patients with mild AD,” the authors wrote in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

“We found that daily 40 Hz audiovisual stimulation for 2 years is safe, feasible, and can slow cognitive decline and biomarker progression, especially in patients with late-onset AD.”

Diane Chan, a former research scientist at the Picower Institute for Learning and Memory and a neurologist at Massachusetts General Hospital, is the study’s lead author and co-author. Picower Professor Li-Huei Tsai, director of the Picower Institute and the Aging Brain Initiative at MIT, is the lead author and co-author of the study.

An “open label” extension

In 2020, MIT enrolled 15 volunteers with mild Alzheimer’s disease in an early-stage trial to evaluate whether an hour a day of 40 Hz light and sound stimulation, delivered through an LED panel and speaker in their homes, could provide clinically significant benefits.

Several studies in mice have shown that sensory stimulation increases the power and synchrony of 40 Hz gamma frequency brain waves, preserves neurons and their network connections, reduces Alzheimer’s proteins such as amyloid and tau, and sustains learning and memory. Several independent groups have also reached similar conclusions over the years.

The MIT trial, although interrupted by the Covid-19 pandemic, found significant benefits after three months. The new study examines results among five volunteers who continued to use their stimulation devices “openly” for two years.

These volunteers returned to MIT for a series of tests 30 months after their initial enrollment. Because four participants began the original trial as controls (meaning they did not initially receive 40 Hz stimulation), its open-label use was six to nine months shorter than the 30-month period.

Testing at 0, 3, and 30 months of enrollment included measurements of brain wave response to stimulation, MRI scans of brain volume, measures of sleep quality, and a series of five standard cognitive and behavioral tests.

Two participants gave blood samples. To compare them with untreated controls, the researchers reviewed three national databases of Alzheimer’s patients, comparing thousands of them on criteria such as age, sex, baseline cognitive scores, and reexaminations at similar times over a 30-month span.

Results and perspectives

The three volunteers with late-onset Alzheimer’s showed improvement or slower decline on most cognitive tests, including significantly positive differences compared to controls on three of them.

These volunteers also showed increased brain wave responsiveness to stimulation at 30 months and showed improvement in measures of circadian rhythms. In the two late-onset volunteers who gave blood samples, there were significant decreases in phosphorylated tau (47 percent for one and 19.4 percent for the other) in a test recently approved by the FDA as the first plasma biomarker to diagnose Alzheimer’s.

“One of the most compelling findings of this study was the significant reduction of plasma pTau217, a biomarker strongly correlated with AD pathology, in the two late-onset patients for whom follow-up blood samples were available,” the authors wrote in the journal.

“These results suggest that GENUS could have direct biological impacts on Alzheimer’s pathology, warranting further mechanistic exploration in larger randomized trials.”

Although the results of the initial trial showed preservation of brain volume at 3 months among those who received 40 Hz stimulation, that was not significant at 30 months.

And the two early-onset male volunteers showed no significant improvements in cognitive test scores. In particular, early-onset patients showed significantly reduced brain wave responsiveness to stimulation.

Although the sample is small, the authors hypothesize that the difference between the two groups of patients is likely attributable to the difference in disease onset rather than the gender difference.

“GENUS may be less effective in patients with early-onset Alzheimer’s disease, potentially due to broad pathological differences with late-onset Alzheimer’s disease that could contribute to differential responses,” the authors wrote. “Future research should explore predictors of treatment response, such as genetic and pathological markers.”

Currently, the research team is studying whether GENUS can have a preventive effect when applied before the onset of the disease. The new trial is recruiting participants over age 55 with normal memory who have or have had a close relative with Alzheimer’s disease, including early-onset.

In addition to Chan and Tsai, the other authors of the article are Gabrielle de Weck, Brennan L. Jackson, Ho-Jun Suk, Noah P. Milman, Erin Kitchener, Vanesa S. Fernandez Avalos, MJ Quay, Kenji Aoki, Erika Ruiz, Andrew Becker, Monica Zheng, Remi Philips, Rosalind Firenze, Ute Geigenmüller, Bruno Hammerschlag, Steven Arnold, Pia Kivisäkk, Michael Brickhouse, Alexandra Touroutoglou, Emery N. Brown, Edward S. Boyden, Bradford C. Dickerson, and Elizabeth B. Klerman.

Funding: Funding for the research came from Freedom Together Foundation, Robert A. and Renee E. Belfer Family Foundation, Eleanor Schwartz Charitable Foundation, Dolby Family, Che King Leo, Amy Wong and Calvin Chin, Kathleen and Miguel Octavio, Degroof-VM Foundation, Halis Family Foundation, Chijen Lee, Eduardo Eurnekian, Larry and Debora Hilibrand, Gary Hua. and Li Chen, The Ko Han Family, Lester Gimpelson, David B Emmes, Joseph P. DiSabato and Nancy E. Sakamoto, Donald A. and Glenda G. Mattes, The Carol and Gene Ludwig Family Foundation, Alex Hu and Anne Gao, Elizabeth K. and Russell L. Siegelman, The Marc Haas Foundation, Dave and Mary Wargo, James D. Cook and Nobert H. Hardner Base.

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About this news about Alzheimer’s disease and neurotechnology research

Author: David Orenstein
Source: MIT Picower Institute
Contact: David Orenstein – MIT Picower Institute
Image: Image is credited to Neuroscience News.

Original research: Open access.
“Gamma sensory stimulation in mild Alzheimer’s dementia: an open-label extension study” by Diane Chan et al. Alzheimer’s and dementia

Abstract

Gamma Sensory Stimulation in Mild Alzheimer’s Dementia: An Open-Label Extension Study

INTRODUCTION

We evaluated the long-term effects of daily 40 Hz (gamma frequency) audiovisual stimulation on cognition and biomarkers in five patients with mild Alzheimer’s disease (AD).

METHODS

For 2 years, patients received daily stimulation for 1 hour. Electroencephalography (EEG) was used to assess neural entrainment; magnetic resonance imaging (MRI) measured brain volumes; activity patterns monitored by actigraphy; Neuropsychological tests assessed cognition; and the S-PLEX assay measured pTau217 in plasma.

RESULTS

No adverse events occurred during the study period. Three female patients with late-onset AD (LOAD) maintained strong EEG entrainment and showed less decline in Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Functional Assessment Scale (FAS) scores compared to matched controls from the National Alzheimer’s Coordinating Center (NACC), Alzheimer’s Disease Neuroimaging Initiative. Alzheimer’s (ADNI) and the Early Onset Longitudinal. Alzheimer’s Disease Study (LEADS). Plasma samples were available for only two of five participants (both with LOAD) and both showed pTau217 reductions of 47% and 19%.

DISCUSSION

These findings suggest that long-term 40 Hz audiovisual stimulation is safe, feasible, and may offer cognitive and biomarker benefits in some people with mild AD, supporting further investigation.

CLINICAL TRIAL REGISTRATION INFORMATION

ClinicalTrials.gov (NCT04055376).