Sound and light therapy shows encouraging results in Alzheimer’s treatment

In the decade since MIT researchers first began exploring how brain waves can be used to combat Alzheimer’s disease, compelling evidence has emerged that specific frequency of neural activity can provide new hope for patients and their families.

A new review published on PLOS Biology on February 28 highlights how the brain can exhibit significant effects at 40 Hz (specific frequencies in the gamma range) in animal models and early human trials, thus providing a potential breakthrough approach that does not rely on drug interventions.

“When we make all the observations, many others in the field have published very stable results. People use many different methods to induce gamma, including sensory stimulation, transcranial alternating stimulation or transcranial magnetic stimulation, but the key is to provide stimulation at 40 Hz. They all see beneficial effects.”

The technique, known as genus (using gamma entrainment of sensory stimulation), uses flashing lights, sound pulses, or tactile vibrations delivered at 40 cycles per second to induce the brain to oscillate at the same frequency. Although the method sounds simple, the results show that it produces complex biological responses, thus jointly hitting various aspects of Alzheimer’s pathology.

Challenges that require new approaches

Alzheimer’s disease affects millions of globally and despite decades of research, there are limited effective treatment options. The traditional approach focuses on managing symptoms or targeting specific disease markers, such as amyloid plaques and tau tangles, with moderate results.

Recently FDA-approved drugs such as Adu and lecanemab show that after 18 months of treatment, they are able to remove amyloid plaques and slowly decrease cognitive abilities by 27-35%. However, these drugs have obvious disadvantages, including high costs and potentially serious side effects, such as brain swelling and bleeding in up to 40% of patients treated with Adu Province.

The researchers noted in the review that the complexity of AD, in which multiple brain regions, circuits, cell types and molecular pathways are compromised, means that targeting a single mechanism does not usually provide a comprehensive benefit,” the researchers noted in the review that multifaceted approaches such as Gamma stimulation may offer specific advantages.

From mouse to person

The trip began in 2016 when Tsai’s team published a discovery in nature that showed that exposing mice to 40 Hz light reduced levels of amyloid beta, a protein associated with Alzheimer’s disease. Subsequent research showed that the method could also be accompanied by sound and tactile stimulation, with its effects beyond the initial brain region.

Perhaps most importantly, these laboratory findings appear to be transforming into humans. The early clinical studies of MIT and cognitive therapeutics from the company that separated from this study showed encouraging results.

“In an early clinical trial, three-month treatment daily reduced brain atrophy (including brain atrophy in the hippocampus) and enhanced functional connectivity measured by synchronously across brain regions. Patients also showed promising cognitive improvement.

Cognito Therapeutics has developed a medical device that provides audiovisual stimulation that is considered safe and well tolerated by patients with Alzheimer’s disease. Results from six months of treatment per day showed a 69% reduction in brain volume loss, including reduced call body atrophy, which is crucial for communication between the two hemispheres. The company has received FDA approval to use its equipment for phase III clinical trials.

Understand the mechanism

What makes the gamma stimulation method particularly attractive is its multifaceted impact on brain biology. Researchers are beginning to understand how 40-Hz oscillations produce these benefits, and recent findings point to several mechanisms.

One approach involves the brain’s waste removal system. Last year, Tsai’s team essentially reported: “40-Hertz audio and visual stimulation caused interneurons in mice to increase the release of peptide VIP, prompting increased amyloid clearance from brain tissue through the brain’s lymphoid gelatinous “plumbing system”.”

A team in China independently confirmed in 2024 that 40-Hz sensory stimulation increases the gelatinous fluid flow in mice, enhancing evidence of this mechanism.

Stimulation also appears to alter the behavior of microglia (the immune cells of the brain), retaining neurons and synapses, and improving blood flow in the brain, resulting in a coordinated response that simultaneously addresses multiple aspects of the disease.

Beyond Alzheimer’s

The comprehensive nature of gamma stimulation effects suggests that it may benefit other neurological diseases. Research shows potential applications of cognitive side effects of Parkinson’s disease, stroke recovery, epilepsy, anxiety, and even chemotherapy.

Researchers at MIT show that audiovisual gamma stimulation protects mice from chemotherapy-induced damage such as brain reduction, DNA damage, inflammation and cognitive deficits. In a mouse model of multiple sclerosis, this treatment relieves demyelination and preserves the functional integrity of the connections connecting the two brain hemispheres.

“The more we understand the mechanism, we have good ideas about how to further optimize treatments,” Tsai said. “And the more we understand the circuits that do it and its effects, the more we can go beyond Alzheimer’s disease and what other neurological diseases will benefit from it.”

The remaining questions

Despite encouraging progress, important issues remain. Researchers are still working to fully understand cellular and molecular changes triggered by gamma stimulation. The MIT team is studying other neuropeptides and neuromodulatory systems to better understand events that link sensory stimulation to observed cellular responses.

Furthermore, methodological variability among different research groups presents challenges. Some labs use portable monitors for speakers, while many larger clinical trials use wearable headphones to provide audio-visual stimulation. There is also a difference in the intensity of the stimulus and the specific wavelength of the light used.

Patient compliance poses another potential barrier. Unlike medications that can be simply swallowed or managed by healthcare professionals, gamma stimulation currently requires patients to self-manage once a day, which may affect consistent and corrective use.

A new era of treatment

Despite these challenges, the field of non-invasive sensory stimulation in neurological conditions is gaining momentum, with multiple research groups facilitating the discovery supporting the therapeutic potential of gamma entrainment.

For the millions of people affected by Alzheimer’s disease worldwide, these advancements offer a promising new direction that is distinct from the success of traditional drug methods. The noninvasiveness of the treatment, combined with its obvious safety and lack of serious side effects, makes it particularly attractive.

“After decades of limited progress, advances in neurotechnology have ushered in a new era of AD treatment,” Park and Tsai concluded in their review. “The emergence of non-invasive 40-Hz sensory stimulation therapy has brought new optimism to patients, caregivers and researchers.”

As Cognito Therapeutics continues its pivotal Phase III clinical trials, researchers around the world further explore the potential of gamma stimulation, the next decade could bring significant advancement to those affected by this destructive situation. Although incurable, this approach offers a new strategy in the ongoing battle against neurodegenerative diseases, a way to use the brain’s own rhythm to combat its decline.