Gamma Light and Sound Therapy for Alzheimer's Disease

Overseen By Remi Philips, BA

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts Institute of Technology

Must not be taking: Amyloid reducers, NMDA antagonists

Disqualifiers: Cancer, Seizure, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 months

50 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, such as amyloid reducing therapy, NMDA receptor antagonists like Memantine, and medications that lower the seizure threshold. If you are on psychiatric medications, you must be on a stable dose for at least three months before joining the trial.

What data supports the effectiveness of the Gamma Light and Sound Therapy treatment for Alzheimer's Disease?

Research shows that 40 Hz sensory therapy, which includes light and sound, has improved cognitive scores in some Alzheimer's patients and is considered safe. Animal studies also suggest it may reduce Alzheimer's-related brain changes, and some participants reported benefits from the therapy. ^{1 2 3 4 5}

Is Gamma Light and Sound Therapy safe for humans?

Small studies in humans have shown that 40 Hz sensory therapy using light and sound is safe and tolerable, with no reported side effects. Further research is needed to explore its effectiveness and feasibility. ^{1 2 3 6 7}

How is the GENUS device treatment different from other Alzheimer's treatments?

The GENUS device treatment is unique because it uses non-invasive light and sound therapy at 40 Hz to stimulate brain activity, which may help improve cognitive function and daily living activities in Alzheimer's patients. Unlike traditional drug treatments, this therapy aims to restore normal brain oscillations and has shown promise in both animal and early human studies without reported side effects. ^{1 3 5 8 9}

What is the purpose of this trial?

Alzheimer's disease (AD) is characterized by significant memory loss, toxic protein deposits amyloid and tau) in the brain, and changes in the gamma frequency band on EEG. The investigator's lab found that boosting gamma waves in AD mouse models using light and sound stimulation at 40Hz not only reduced amyloid and tau in the brain, but also improved memory. The investigators developed a light and sound device for humans that stimulates the brain at 40Hz that can be used safely at home. For the present study, 60 participants with mild Alzheimer's disease will be enrolled and will use this light and sound device at-home daily for 6-months. Investigators will measure changes in brain waves with EEG, blood biomarkers, the microbiome via fecal samples, functional and structural MRI scans, memory and cognitive testing, and questionnaires at 3 in-person visits throughout the study. After the 6-month time point, participants will have the option of continuing in the study for one additional year and completing an 18-month study visit. This study will provide critical insight into extended therapy involving non-invasive 40Hz sensory stimulation as a possible therapeutic strategy for mild to moderate Alzheimer's disease.

Research Team

Li Huei Tsai, PhD

Principal Investigator

Massachusetts Institute of Technology

Eligibility Criteria

This trial is for individuals aged 50-100 with mild Alzheimer's disease, having an MMSE score of 19-26. They must be able to give consent or have a representative do so and complete the first month at their primary residence. Excluded are those without healthcare, on certain Alzheimer's medications, unstable psychiatric treatments, seizure history within two years, significant suicide risk, behavioral issues affecting compliance, recent stroke or eye surgery candidates.

Inclusion Criteria

If I can't consent, someone legally allowed will do it for me.

I am between 50 and 100 years old.

I have mild Alzheimer's with a specific cognitive test score.

Exclusion Criteria

Subjects who have an active implantable medical device including but not limited to implantable cardioverter defibrillator (ICD), deep brain stimulator (DBS), cardiac pacemaker, and/or sacral nerve stimulator

Subjects with behavioral problems such as aggression/agitation/impulsivity that might interfere with their ability to comply with protocol

Subjects who have >3 microbleeds/microhemmorhages in their brain

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants use a gamma light and sound device at-home daily for 6 months, with 3 in-person visits for assessments

6 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment for one additional year with guaranteed 40Hz active treatment

12 months

1 visit (in-person) at 18 months

Treatment Details

Interventions

• GENUS device

Trial Overview The study tests a device called GENUS that uses light and sound at 40Hz aimed to stimulate brain waves in people with mild Alzheimer's disease. Participants will use this device daily for six months at home while undergoing various assessments including EEGs, MRIs, cognitive tests and questionnaires to evaluate its effects on brain function and memory.

Participant Groups

Group I: Alzheimer's Active Arm Active Control 1 Intervention

Exposure to active sensory stimulation (40Hz) for 60 minutes daily for the length of the trial (6 months).

Group II: Alzheimer's Control Arm Placebo Group 1 Intervention

Exposure to control stimulation (sham) for 60 minutes daily for the length of the trial (6 months).

GENUS device is already approved in United States for the following indications:

Approved in United States as 40Hz Light and Sound Therapy for:

• Alzheimer's disease

Who Is Running the Clinical Trial?

Massachusetts Institute of Technology

Lead Sponsor

Trials

104

Recruited

12,810,000+

Findings from Research

Gamma Entrainment Using Sensory stimulation (GENUS) shows promise as a non-pharmacological treatment for Alzheimer's disease, with animal studies indicating it can positively affect cognitive decline and reduce amyloid plaques and neurofibrillary tangles.

Although research on GENUS in humans is still in early stages, initial findings suggest it is feasible and warrants further investigation to establish its effectiveness as a disease-modifying intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the use of gamma (multi)sensory stimulation for Alzheimer's disease treatment. Manippa, V., Palmisano, A., Filardi, M., et al.[2023]

A study involving 10 patients with mild cognitive impairment due to Alzheimer's disease demonstrated that daily 1-hour sessions of gamma flicker stimulation (40 Hz) were safe, well-tolerated, and adhered to over 4 to 8 weeks.

Preliminary results indicated that this gamma flicker stimulation may positively influence neural activity and immune factors in the nervous system, suggesting potential benefits for further research in Alzheimer's treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A feasibility trial of gamma sensory flicker for patients with prodromal Alzheimer's disease. He, Q., Colon-Motas, KM., Pybus, AF., et al.[2022]

A non-invasive 40 Hz sensory therapy using light and sound was found to be safe and tolerable in a small group of 27 participants with Mild Cognitive Impairment (MCI) or Alzheimer's Disease (AD), with 11 completing 6 months of therapy.

Some participants showed cognitive improvements, with 2 out of 4 with subjective complaints and 2 out of 6 with AD improving their Montreal Cognitive Assessment (MOCA) scores, suggesting potential benefits of this therapy that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Feasibility Study of AlzLife 40 Hz Sensory Therapy in Patients with MCI and Early AD. McNett, SD., Vyshedskiy, A., Savchenko, A., et al.[2023]

A self-luminous light table effectively increased sleep duration and efficiency in individuals with Alzheimer's disease over a four-week intervention, compared to a baseline week.

The use of this light table also significantly reduced agitation and depression scores, highlighting its potential as a practical treatment method for improving sleep and mood in dementia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Research Note: A self-luminous light table for persons with Alzheimer's disease. Figueiro, MG., Plitnick, B., Rea, MS.[2020]

The 11-week study involving 35 individuals with Alzheimer's disease and related dementia showed that a tailored lighting intervention significantly improved circadian entrainment and sleep efficiency, while also reducing depression symptoms in participants.

Caregivers also benefited from the lighting intervention, experiencing improved circadian rhythms, sleep efficiency, and longer sleep duration, suggesting that this approach could be beneficial for other populations with sleep issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tailored Lighting Intervention for Persons with Dementia and Caregivers Living at Home. Figueiro, MG., Hunter, CM., Higgins, P., et al.[2022]

Photobiomodulation therapy shows promise as a novel treatment for Alzheimer's disease, with demonstrated safety in humans and effective doses identified in animal models, suggesting it could be a viable option for preventing and treating dementia.

The review emphasizes the need for large-scale clinical trials to further investigate this therapy, as it has already shown positive results in preliminary studies and could help address the growing number of Alzheimer's cases expected in the coming decades.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photobiomodulation for Alzheimer's Disease: Translating Basic Research to Clinical Application. Enengl, J., Hamblin, MR., Dungel, P.[2021]

The RGn500 device, which combines photonic and magnetic emissions, showed a neuroprotective effect in a mouse model of Alzheimer's disease when applied daily for 10 minutes, leading to memory restoration and normalization of key Alzheimer's markers.

This treatment demonstrated similar therapeutic efficacy to traditional pharmacological approaches, suggesting it could be a promising alternative for managing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroprotective effect of a new photobiomodulation technique against Aβ25-35 peptide-induced toxicity in mice: Novel hypothesis for therapeutic approach of Alzheimer's disease suggested. Blivet, G., Meunier, J., Roman, FJ., et al.[2022]

A 6-month study involving 22 patients with mild to moderate Alzheimer's disease showed that daily 40 Hz gamma sensory stimulation therapy was well tolerated and helped maintain functional abilities, unlike the sham group which experienced a decline.

Patients receiving the active treatment had improved sleep quality, as indicated by reduced nighttime activity, suggesting that gamma sensory stimulation may have beneficial effects on both sleep and cognitive function in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer's Disease Patients. Cimenser, A., Hempel, E., Travers, T., et al.[2021]

In a study of 1,464 subjects aged 0-91, 40Hz intermittent photic stimulation (IPS) induced gamma oscillations in the brain, showing a statistically significant but minor effect of age on amplitude change, indicating that older individuals still respond to this stimulation.

The study found that while age affects the detection probability of induced gamma peaks, it does not significantly alter the magnitude or spatial distribution of the response, suggesting that photic stimulation could be a viable therapeutic approach for Alzheimer's patients regardless of age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma Entrainment in a Large Retrospective Cohort: Implications for Photic Stimulation Therapy for Alzheimer's Disease. Zibrandtsen, IC., Agger, M., Kjaer, TW.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

An update on the use of gamma (multi)sensory stimulation for Alzheimer's disease treatment. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

A feasibility trial of gamma sensory flicker for patients with prodromal Alzheimer's disease. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A Feasibility Study of AlzLife 40 Hz Sensory Therapy in Patients with MCI and Early AD. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Research Note: A self-luminous light table for persons with Alzheimer's disease. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Tailored Lighting Intervention for Persons with Dementia and Caregivers Living at Home. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Photobiomodulation for Alzheimer's Disease: Translating Basic Research to Clinical Application. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Neuroprotective effect of a new photobiomodulation technique against Aβ25-35 peptide-induced toxicity in mice: Novel hypothesis for therapeutic approach of Alzheimer's disease suggested. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer's Disease Patients. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Gamma Entrainment in a Large Retrospective Cohort: Implications for Photic Stimulation Therapy for Alzheimer's Disease. [2021]