Exploring Flashing Lights and Sounds to Slow Alzheimer’s Brain Shrinkage

By | May 7th, 2024

Cognito Therapeutics' experimental headset, Spectris, uses a specific frequency of flickering lights and sounds to stimulate the brain in people with Alzheimer’s disease — and it’s heading to Phase 3 trials.

As the vast majority of Alzheimer’s drugs fail in clinical trials, some researchers and companies are turning to non-invasive neurotechnology as an alternative approach to treatment. People with Alzheimer’s disease have altered brain function, so some makers of experimental devices are asking: Is it possible to zap or stimulate the brain back to health? 

An experimental headset developed by Cognito Therapeutics, called Spectris, uses flickering lights and sounds at a specific frequency—40 Hz —to stimulate brain activity. The goal is to restore “gamma oscillations” in the brain; if neurons are synchronized swimmers, the gamma oscillations are a difficult dance move that is an integral part of their performance. In Alzheimer’s, the synchronized swimmers can’t do the dance required for memory and cognitive function as well as they used to. Spectris helps the synchronized swimmers of the brain regain their ability to do that dance routine.

According to results from its recent Phase 2 trial, the device was safe and slowed functional decline and brain shrinkage over six months of use. Susan Landau, a neuroscientist at the University of California, Berkeley, who wasn’t involved in the study, told Being Patient that the results were “encouraging” and “impressive.”  

While other companies sell products that produce 40 Hz light stimulation, their devices have not been subject to the same level of rigorous clinical trials to see if they actually work as advertised, and are not approved as medical devices for treating Alzheimer’s or dementia.

Images courtesy Cognito Therapeutics

Breaking down the Phase 2 trial

The company’s Phase 2 trial enrolled 76 participants over the age of 50 who were diagnosed with Alzheimer’s disease, using clinical criteria. This is different from studies of anti-amyloid drugs which require patients to have beta-amyloid plaques or tau pathology in their brains. In this study, a total of 20 participants were amyloid-negative.

“Since our therapeutic mechanism does not target removal of amyloid plaque, we did not require a minimal threshold of amyloid plaque as determined by PET scans for patients in our study,” Brent Vaughan, CEO of Cognito Therapeutics, told Being Patient.

Two thirds of the participants received the active treatment, while one-third received a sham treatment—they had the same headset, but it wasn’t calibrated to flicker lights and sounds at the right frequency for gamma oscillations. Using a sham control helps the researchers know for certain that the effects they see are the result of gamma oscillations rather than general brain stimulation or a placebo effect.

Participants had to use the device daily for one hour over six months. “While using the device people can be sitting, resting, or lying down,” Vaughan said. “They are not able to watch TV or listen to music.” 

This didn’t seem like a dealbreaker as 77 percent of participants who received the treatment completed the study. (The company is also evaluating new versions of the device that could be used while reading or watching TV.)

There were no serious side effects for patients enrolled in the study either, though about one in five experienced headaches and about one in seven experienced tinnitus.

All participants showed some decline in their ability to live independently, and in their cognition. However, those in the treatment group declined by 6.61 points less on a 78-point scale that measures their ability to do tasks like dressing themselves, eating independently, or going for walks on their own. 

“Patients may experience enhanced abilities in tasks such as remembering where their keys are, engaging in social activities, and maintaining independence in daily routines,” Vaughan said.

The patients who received the treatment also showed a 69 percent slowing in overall brain shrinkage, but the researchers did not see an effect on amyloid clearance.

The study used multiple tests to measure brain function and memory—only one found that the treatment slowed cognitive decline by a bit. Landau noted that six months may be too short to notice significant changes in cognitive decline and that a larger time-frame might be needed to better assess these effects.

After the trial, all participants had the opportunity to continue treatment. Those who received the sham treatment showed a slowing of brain shrinkage and functional decline after switching over to the treatment. 

“These results provide support for the potential safety of prolonged treatment and highlight the potential for Spectris as a potential disease modifying therapy to preserve both brain structure and function in patients with Alzheimer’s disease,” said Vaughan in a press release.

What do the results mean for patients?

The Phase 2 study showed that the Spectris device might prevent neurodegeneration and potentially treat some of the functional decline in Alzheimer’s without touching amyloid in the brain. 

Vaughan told Being Patient that since the mechanism of the treatment doesn’t involve amyloid, it could be paired with anti-amyloid drugs like Leqembi to boost the benefits for patients and may be useful for other neurodegenerative diseases like Parkinson’s or multiple sclerosis. 

Landau came to similar conclusions. “The treatment may be useful for a broader group of individuals with dementia,” she said, though she emphasized that it may not be disease-modifying specifically for Alzheimer’s which is now defined by amyloid and tau biomarkers in the brain. She added that longer and larger trials will be needed.

Who could potentially benefit from the treatment?

Some patients might not take anti-amyloid drugs like Leqembi because they take certain medications or have the APOE4 Alzheimer’s risk gene, putting them at risk of brain swelling and brain bleeds. In contrast, a broad swathe of patients might benefit from Spectris. 

Cognito Therapeutics screened for patients whose brains produced gamma oscillations in response to 40 Hz lights and sounds. “We believe this may be a predictive biomarker for response to treatment,” Vaughan said. About 85 to 90 percent of the patients screened across multiple trials have this response.  

Since the device is still a few years out from filing for approval, Vaughan said it is too early to speculate on how much it would cost. The company is currently recruiting patients for its 12-month Phase 3 trial and afterward will file for approval from the FDA as a medical device. 

“It is hard to know how these effects will translate in a larger sample and longer study,” Landau said. “I’m sure the study [offers] hope that the effects will be bigger with more participants, but that doesn’t always happen.”

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