First Feasibility Study Shows Flickering Lights and Sounds Could Be New Weapon Against Alzheimer’s Disease

In recent years, Annabelle singer and his collaborators used flickering lights and sounds to treat mouse models of Alzheimer’s disease, and they’ve seen dramatic results.

Now they have the results of the first human feasibility study of the flicker treatment, and they are showing promise.

“We looked at safety, tolerability, and adhesion, as well as several different biological results, and the results were excellent – better than we expected,” said Singer, assistant professor in the Department of Biomedical Engineering at Wallace. H. Coulter at Georgia Tech and Emory.

Singer shared the preliminary results of the feasibility study in October at the American Neurological Association’s annual meeting. Now she is a corresponding author with neurology researcher Emory James lah of an article presenting their findings in the journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions.

The flicker treatment stimulates gamma waves, manipulates neuronal activity, recruits the brain’s immune system, and kills pathogens – in short, leads a successful fight against a progressive disease that still has no cure.

Previous research had already shown that sensory areas of the human brain cause flickering stimuli for seconds to hours. But it was the first time that Singer and his team could test gamma sensory stimulation over a long period of time.

The study included 10 patients with mild cognitive impairment associated with Alzheimer’s disease, which required them to wear an experimental visor and headphones that exposed a group to light and sound at 40 hertz for an hour a day. for eight weeks, and another group for four weeks after a delayed start.

“We were able to set the devices to a level of light and sound that was not only tolerable, but also successfully elicited an underlying brain response,” Lah said.

As they hoped and expected, Singer said, “the training was rampant.” That is, brain activity – in this case, gamma waves – synchronized with external stimulation.

Gamma waves are associated with high-level cognitive functions, such as perception and memory. Disturbances of these waves have been found in various neurological disorders, not just Alzheimer’s disease.

The human feasibility study has shown that the treatment of gamma flicker is safe and tolerable. And perhaps most surprisingly, the patients went through the full treatment program.

“Membership was one of our main concerns,” Singer said. “When we sent the device home with the participants, were they using it? Would they use it for a few days, and that would be it? We were pleasantly surprised that this was not the case.

Compliance rates hovered around 90%, with no serious adverse effects reported during the study or the 10-month open-label extension (some patients even volunteered to continue to be monitored and evaluated after the study. , although this data is not part of the published research.).

Some participants reported mild discomfort that could have been related to the flickering – dizziness, ringing in the ears, and headache. But overall, Singer said, the device’s security profile was excellent. She also reported positive biological results.

“We looked at default mode network connectivity, which is basically how different regions of the brain that are particularly active during awake rest and memory, interact with each other,” Singer said. “There are deficits in this network in Alzheimer’s disease, but after eight weeks [of treatment], we have seen a strengthening of this connectivity. This may indicate stronger interactions and therefore better communication between these regions.

In previous animal studies, 40 Hz gamma waves from mice stimulated flicker, significantly reducing certain pathogenic features of Alzheimer’s disease and microglia recruited to the cause – these are the brain’s main immune cells. But in the human study, there was no clear change in the presence of pathogens beta amyloid or p-Tau.

However, as with the mouse studies, “we get immune engagement in humans,” Singer said. Treatment of the flicker triggered the activity of cytokines, proteins used in cell signaling – a sign that the flicker had engaged the brain’s immune system.

“This is something we want to see, because the microglia do things like kill pathogens. Some people think that part of what’s wrong with Alzheimer’s disease is a failure of this release mechanism, ”Singer said.

She and Lah wondered if a longer human trial would make a difference – would there be reduced amyloid activity, for example.

“So far this is very preliminary, and we are far from drawing any conclusions about the clinical benefit of this treatment,” Lah said. “But now we have a very good case for a larger, longer study with more people.”

The study was funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (grant # R01-NS109226-01S1), the Packard Foundation, the Friends and Alumni of Georgia Tech, the Lane family, the family Wright and Cognito Therapeutics. All findings, conclusions and recommendations are those of the researchers and not necessarily of the sponsors.

Competing interests: Annabelle Singer owns a stake in Cognito Therapeutics, which funded the human study at the Emory Brain Health Center. Cognito aims to develop products related to gamma stimulation. These conflicts are managed by Georgia Tech’s Office of Research Integrity Assurance.