In a new medRxiv preprint, scientists from the Massachusetts Institute of Technology (MIT) reported that stimulating the brain with 40 Hz of pulsing lights and sounds was safe and reduced early signs of structural brain changes associated with Alzheimer’s disease progression. Patients with mild signs of Alzheimer’s disease also developed more stable circadian rhythms and performed better on cognitive tests during the three-month long clinical trial.
“This is just the beginning, and these are very encouraging results,” said Sylvain Williams, a neuroscientist at McGill University, who was not involved in the study.
The treatment works by modifying gamma oscillations, which are waves of electrical activity in the brain associated with higher cognitive functions like attention and memory. Alzheimer’s disease patients often have disrupted gamma oscillations. Previously, the same team of MIT researchers, led by Li-Huei Tsai, showed that they could increase gamma oscillations in the brain of a mouse model of Alzheimer’s disease by stimulating the brain with sound and light at 40 pulses per second using a device called Gamma Entrainment Using Sensory Stimuli (GENUS). Treatment with the GENUS device reduced levels of amyloid beta plaques in the mouse brains and improved their memory.
While the results of GENUS treatment looked promising in mice, scientists did not know if the same technique could work in humans until now.
Tsai’s team tested the safety and efficacy of GENUS in humans in two different clinical trials. They found that GENUS successfully induced 40 Hz gamma oscillations in cognitively normal young adults, older adults, and patients with mild dementia associated with Alzheimer’s disease. None of the groups experienced any adverse side effects from the treatment, including two additional patients with epilepsy.
“They've shown that their method actually works in humans in terms of getting the brain to oscillate at 40 Hz,” Williams said.
To test the effectiveness of GENUS in Alzheimer’s disease patients, the team performed a randomized, placebo-controlled clinical trial with patients with probable mild Alzheimer’s disease. Eight patients received the light and sound stimulation at 40Hz treatment, and seven listened to white noise and watched constant white light in the control condition.
After three months of daily use, the brains of the people in the treatment group showed less ventricular enlargement, a hallmark of Alzheimer’s disease progression, and their hippocampus volumes remained unchanged. Using fMRI, the team also found increased connectivity in brain circuits important for sensory processing and memory in the GENUS-treated patients.
Patients with Alzheimer’s disease often also have disrupted circadian rhythms, but after four months of GENUS treatment, the stability of circadian rhythms in these patients improved. And, after three months of treatment, patients showed significant improvement in a face-name association test, suggesting improved cognition.
“It is surprising to actually see some of the effects already after three months, so it is very encouraging for long term treatments,” Williams said.
While these results look promising, the team hopes to study the effectiveness of GENUS in larger and longer clinical trials soon.
“This is the first paper of a large number of papers that is going to be published on this. I know there's a lot of excitement in the field,” said Williams. “It is going to be interesting to follow this for certain. It's such a striking method.”
Chan, D. et al. Gamma Frequency Sensory Stimulation in Probable Mild Alzheimer’s Dementia Patients: Results of a Preliminary Clinical Trial. Preprint at: https://www.medrxiv.org/content/10.1101/2021.03.01.21252717v3.full-text (2021).