Five people with Alzheimer’s disease kept sitting in front of LED panels and speakers for two years, receiving an hour of 40-hertz light and sound stimulation each day. Three of them, all women with late-onset Alzheimer’s, performed significantly better on cognitive tests than comparable patients who received no treatment. Two showed substantial drops in tau proteins, the molecular tangles that clog neurons in Alzheimer’s brains.

The results, published in Alzheimer’s & Dementia, represent the longest follow-up yet for a treatment called GENUS (gamma entrainment using sensory stimuli). The approach works by using precisely timed flashes and clicks to boost gamma brain waves at 40 hertz, a frequency associated with neural synchrony and waste clearance in the brain. MIT researchers first showed the method worked in mice, preserving neurons and reducing Alzheimer’s proteins. Then they tested it in people.

A Pandemic Cut the Trial Short

The original 2020 trial enrolled 15 volunteers but got derailed by COVID-19 after just three months. Still, those initial results showed promise. Five participants decided to keep using the devices at home on an open-label basis (meaning they knew what treatment they were getting). These five returned to MIT for testing 30 months after enrollment, creating an unusual dataset: a small group of people who stuck with an experimental treatment for roughly two years.

The testing included brain wave measurements, MRI scans, sleep quality assessments, and five standard cognitive tests. To compare outcomes, researchers combed through three national Alzheimer’s databases, matching thousands of patients on age, gender, initial cognitive scores, and similar timepoints.

The study authors note: “We found that daily 40Hz audiovisual stimulation over 2 years is safe, feasible, and may slow cognitive decline and biomarker progression, especially in late-onset AD patients.”

Why It Worked for Some and Not Others

The three women with late-onset Alzheimer’s showed improvement or slower decline on most cognitive measures, with statistically significant differences on three tests compared to controls. Their brain wave responses to the stimulation actually increased at 30 months. One woman’s plasma showed a 47 percent drop in phosphorylated tau-217; another showed a 19.4 percent decrease. The FDA recently approved this tau marker as the first plasma biomarker for diagnosing Alzheimer’s.

The researchers emphasize the significance: “One of the most compelling findings from this study was the significant reduction of plasma pTau217, a biomarker strongly correlated with AD pathology, in the two late-onset patients in whom follow-up blood samples were available. These results suggest that GENUS could have direct biological impacts on Alzheimer’s pathology, warranting further mechanistic exploration in larger randomized trials.”

The two men with early-onset Alzheimer’s saw no benefits. Their brain wave responsiveness to stimulation actually decreased over time. The researchers suspect the difference relates to disease onset rather than gender, since early-onset and late-onset Alzheimer’s involve different pathological processes.

The study acknowledges this divide: “GENUS may be less effective in early onset Alzheimer’s disease patients, potentially owing to broad pathological differences from late-onset Alzheimer’s disease that could contribute to differential responses. Future research should explore predictors of treatment response, such as genetic and pathological markers.”

Five people is a tiny sample. But for a treatment that involves no drugs, no surgery, and no apparent side effects, the results are intriguing enough that a nationwide phase III trial is already underway through MIT spinoff company Cognito Therapeutics. The researchers are also testing whether the stimulation might work as a preventative measure in people aged 55 and older with normal memory but a family history of Alzheimer’s.

Lead author Diane Chan, formerly at MIT’s Picower Institute and now at Massachusetts General Hospital, worked alongside Picower Professor Li-Huei Tsai, who directs both the institute and MIT’s Aging Brain Initiative. Whether sitting in front of flickering lights for an hour a day can genuinely slow Alzheimer’s remains an open question. But for three people, it seems to have helped.

Journal: Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association
Article: Gamma sensory stimulation in mild Alzheimer’s dementia: an open-label extension study