A pair of early stage clinical studies testing the safety and efficacy of 40Hz sensory stimulation to treat Alzheimer’s disease has found that the potential therapy was well tolerated, produced no serious adverse effects and was associated with some significant neurological and behavioral benefits among a small cohort of participants.
“In these clinical studies we were pleased to see that volunteers did not experience any safety issues and used our experimental light and sound devices in their homes consistently,” said Li-Huei Tsai, Picower Professor in the The Picower Institute for Learning and Memory at MIT and senior author of the paper describing the studies in PLOS ONE Dec. 1. “While we are also encouraged to see some significant positive effects on the brain and behavior, we are interpreting them cautiously given our study’s small sample size and brief duration. These results are not sufficient evidence of efficacy, but we believe they clearly support proceeding with more extensive study of 40Hz sensory stimulation as a potential non-invasive therapeutic for Alzheimer’s disease.”
In three studies spanning 2016-2019, Tsai’s lab discovered that exposing mice to light flickering or sound clicking at the gamma-band brain rhythm frequency of 40Hz — or employing the light and sound together — produced widespread beneficial effects. Treated mice modeling Alzheimer’s disease pathology experienced improvements in learning and memory; reduced brain atrophy, neuron and synapse loss; and showed lower levels of the hallmark Alzheimer’s proteins amyloid beta and phosphorylated tau compared to untreated controls. The stimulation appears to produce these effects by increasing the power and synchrony of the 40Hz brain rhythm, which the lab has shown profoundly affects the activity of several types of brain cells, including the brain’s vasculature.
Study designs
Based on those encouraging results, Diane Chan, a neurologist at Massachusetts General Hospital and a postdoctoral clinical fellow in Tsai’s lab, led the two new clinical studies at MIT. One set of tests, a “Phase 1” study, enrolled 43 volunteers of various ages including 16 people with early stage Alzheimer’s to confirm that exposure to 40Hz light and sound was safe and test whether it increased 40Hz rhythm and synchrony after a few minutes of exposure, as measured with EEG electrodes. The study also included two patients with epilepsy at the University of Iowa who consented to having measurements taken in deeper brain structures during exposure to 40Hz sensory stimulation while undergoing epilepsy-related surgery.
The second set of tests, a “Phase 2A” pilot study, enrolled 15 people with early stage Alzheimer’s disease in a single-blinded, randomized, controlled study to receive exposure to 40Hz light and sound (or non-40Hz “sham” stimulation for experimental controls) for an hour a day for at least three months. They underwent baseline and follow-up visits including EEG measurements during stimulation, MRI scans of brain volume, and cognitive testing. The stimulation device the volunteers used in their homes (a light panel synchronized with a speaker) was equipped with video cameras to monitor device usage. Participants also wore sleep-monitoring bracelets during their participation in the trial.
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