Summary: A multi-year, open-label follow-up study reports that daily 40Hz light-and-sound stimulation (GENUS) may slow cognitive decline and reduce a key Alzheimer’s biomarker in people with late-onset Alzheimer’s disease. Over roughly two years of at-home treatment, late-onset participants preserved stronger cognitive performance than matched patients in national datasets and showed notable reductions in plasma tau protein levels.
GENUS (gamma entrainment using sensory stimuli) is a noninvasive therapy that delivers synchronized 40Hz visual and auditory stimulation to entrain brain activity at gamma frequencies. While benefits appeared strongest in late-onset cases, the findings support further research of this safe, at-home neuromodulation approach to delay Alzheimer’s progression.
Key Facts
- Sustained cognitive effects: Participants with late-onset Alzheimer’s maintained higher scores on several cognitive assessments across two years compared with matched controls.
- Biomarker improvement: Two late-onset participants who provided blood samples showed large reductions in phosphorylated tau (pTau217), a plasma biomarker linked to Alzheimer’s pathology.
- Safe and feasible: Daily one-hour GENUS sessions at home were well tolerated and produced no reported adverse events during the study period.
Source: Picower Institute at MIT
Overview of the study
This open-label extension examined five volunteers who continued daily 40Hz audiovisual stimulation for about two years after participating in an early-stage MIT trial. The follow-up focused on cognition, EEG entrainment, sleep and circadian measures, brain structure, and plasma biomarkers. Although the sample is small, these data represent the longest continuous home use of GENUS reported to date.
Three of the volunteers had late-onset Alzheimer’s disease (LOAD) and were female; they showed preserved cognitive performance on multiple tests and improved markers of circadian rhythm. Two male volunteers with early-onset Alzheimer’s disease did not show comparable improvements and demonstrated weaker EEG entrainment to the stimulus.
Study design and methods
Originally, 15 people with mild Alzheimer’s were enrolled in an MIT pilot trial to evaluate one hour per day of synchronized 40Hz light and sound delivered by an LED panel and speaker in participants’ homes. The pandemic shortened the initial study, but five volunteers continued device use on an open-label basis. Assessments occurred at baseline, three months, and roughly 30 months after initial enrollment and included:
- Electroencephalography (EEG) to measure neural entrainment at 40Hz
- Magnetic resonance imaging (MRI) to monitor brain volume
- Actigraphy to track sleep and circadian rhythms
- A battery of standardized cognitive and behavioral tests
- Plasma assays (S-PLEX) for phosphorylated tau (pTau217) where blood samples were available
Key results
No adverse events were reported across the two-year follow-up. The three female participants with late-onset Alzheimer’s retained robust EEG entrainment to the 40Hz stimulation and showed either improved or more slowly declining results on cognitive measures, such as MMSE, CDR, and functional assessments, compared to demographically matched controls from national Alzheimer’s cohorts. These late-onset participants also displayed improved activity patterns consistent with healthier circadian rhythms.
Plasma samples were available for two of the late-onset participants; both showed reductions in pTau217 (approximately 47% and 19%), a plasma biomarker recently recognized as strongly correlated with Alzheimer’s pathology. The early-onset participants demonstrated reduced EEG responsiveness and did not show significant cognitive gains, suggesting potential differences in treatment responsiveness by disease subtype.
Interpretation and implications
The authors conclude that long-term daily 40Hz audiovisual stimulation is safe, feasible for home use, and may provide cognitive and biomarker benefits for some individuals with mild, late-onset Alzheimer’s disease. The observed decreases in plasma pTau217 in two participants suggest possible biological effects on disease pathology and support the need for larger, randomized trials to confirm efficacy and explore mechanisms.
The differing responses between late-onset and early-onset participants may reflect underlying pathological and genetic distinctions between these subtypes of Alzheimer’s disease. Future research should investigate predictors of response, including genetic markers and detailed pathology, and evaluate whether earlier preventative application of GENUS—before symptom onset—might reduce risk or delay disease progression.
Study authors and acknowledgements
The study was led by Diane Chan (Picower Institute and Massachusetts General Hospital) and senior-author Li-Huei Tsai (Picower Institute, MIT). Additional co-authors include 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: The research received support from multiple foundations and private donors, including philanthropic organizations and family foundations that supported study activities and operations.
Frequently asked questions
A: GENUS stands for gamma entrainment using sensory stimuli. It uses synchronized 40Hz light and sound to promote gamma-frequency brain activity that is associated with memory and cognitive processing.
A: In this small study, people with late-onset Alzheimer’s disease showed slower cognitive decline, improved circadian activity patterns, stronger EEG entrainment, and reductions in plasma phosphorylated tau in the participants who provided blood samples.
A: The researchers suggest early-onset Alzheimer’s may involve different or broader pathological changes than late-onset disease, potentially reducing responsiveness to gamma-based sensory stimulation. Larger studies are needed to explore these differences.
About this research
Author: David Orenstein
Source: Picower Institute at MIT
Contact: David Orenstein, Picower Institute at MIT
Image credit: Neuroscience News
Original research: Open access. Title: “Gamma sensory stimulation in mild Alzheimer’s dementia: an open-label extension study” by Diane Chan et al., published in Alzheimer’s & Dementia.
Abstract (concise)
Introduction: This study assessed long-term effects of daily 40Hz audiovisual stimulation on cognition and biomarkers in five patients with mild Alzheimer’s disease.
Methods: Over two years, participants received one hour of daily stimulation. EEG evaluated neural entrainment; MRI tracked brain volumes; actigraphy measured sleep and activity patterns; neuropsychological tests assessed cognition; and S-PLEX assays measured plasma pTau217.
Results: No adverse events occurred. Three female late-onset patients maintained EEG entrainment and showed less cognitive decline than matched controls. Two late-onset participants with available plasma samples demonstrated pTau217 reductions of 47% and 19%.
Discussion: Long-term 40Hz audiovisual stimulation appears safe and feasible and may provide cognitive and biomarker benefits for some individuals with mild late-onset Alzheimer’s, justifying larger randomized trials.
Clinical trial registration: ClinicalTrials.gov NCT04055376 (study registration information).