Brain Wave

by Mind Over Matter V 13:

Light & Sound Treatment for Alzheimer’s Disease

Your brain bustles with electrical activity all the time, with your neurons sending each other electrical signals to communicate (in addition to communicating with each other via chemical neurotransmitters). The term “brain wave” is used to describe a rhythmic pattern in the brain’s electrical activity, produced when large groups of neurons fire on and off together at a certain frequency. 

There are five widely recognized brain wave frequencies, each associated with specific mental states and neurological functions. One brain wave frequency may be dominant in the brain at any given time, but all frequencies are always present to some degree.

GAMMA BRAIN WAVES ARE DISRUPTED IN NEUROLOGICAL CONDITIONS

Gamma brain waves are of specific interest to dementia researchers because they can be significantly disrupted as we age, especially in people with age-related, progressive neurological disorders such as Alzheimer’s disease (AD) and frontotemporal dementia. (Gamma brain waves are associated with multiple brain functions, including attention, cognitive processing, and memory.)

BRAIN WAVES RESPOND TO SENSORY INPUT

In a phenomenon referred to as “brain wave entrainment,” our brains tend to fall into sync with the rhythm of an external stimulus. For example, brains exposed to sound, light, or touch sensations that are vibrating within the range of brain wave frequencies can begin to generate brain waves in a matching rhythm.

GAMMA BRAIN WAVE ENTRAINMENT & AD

Knowing that brain waves can be altered by sensory input, and that gamma waves in particular are irregular in individuals with AD, researchers were curious about whether exposure to pulses of light and sound delivered in the gamma frequency range could be a treatment for the disease. 

Initial explorations into that possibility began with studies using mice that were genetically engineered to exhibit hallmark symptoms of AD. Research studies that exposed the mice to light and sound oscillating at 40 Hertz (Hz) revealed some promising results, including a significant reduction in AD pathogenic hallmarks in the brain, and altered immune cells and signaling. 

Based on the exciting initial findings in mice, researchers began studying the effects of gamma audio-visual stimulation on humans. 

One human trial involving 40 Hz audio-visual stimulation was conducted by Dr. Annabelle Singer and colleagues. In the study, published in May 2021 in Alzheimer’s & Dementia, ten participants with mild cognitive impairment due to underlying AD were exposed to the stimulation at home via light-emitting goggles and sound-emitting headphones for one hour each day. 

The study took place over eight weeks, with half of the participants receiving the gamma treatment for the full eight weeks, and the other half starting midway through and receiving the treatment for the final four weeks. The researchers looked at safety, tolerance, and adherence, along with several biological outcomes, and found the results in all areas were excellent. 

“Although some participants reported occasional mild discomfort, there were no serious adverse events related to the treatment and overall, the device was found to be very safe,” said Dr. Singer, Assistant Professor at Georgia Institute of Technology and Emory University. 

“Because the stimulation itself is not inherently rewarding, we wondered if participants would use the device for the prescribed 
one hour per day for the duration of the study. We were pleased to discover that they did, with participants completing 95.5% of treatments on average.”

Further, magnetic resonance imaging (MRI) scans and cerebral spinal fluid collected as part of the research provided preliminary evidence that the treatment affected neural networks and immune factors in the nervous system. Specifically, they found that the treatment strengthened connectivity in the default mode network – which is important for interactions across brain regions involved in memory and tends to be compromised in cases of AD. 

In addition, the researchers found altered levels of cytokines (proteins used in cell signaling), which indicates that the stimulation affects the brain’s immune system. The researchers believe that the brain's immune system plays a key role in AD progression and the effects of this treatment.

Of note, these human participants did not experience the decrease in amyloid-beta or tau (two proteins commonly associated with AD) that had been found in the mice research. “We expect human brains need more time to experience a drop in Alzheimer’s hallmarks, compared to mice,” said Dr. Singer. “More research is needed to explore that possibility and learn more about the potential clinical benefits of this treatment. These findings are preliminary, but they do support the case for longer studies with larger groups of people.”

Multiple studies of gamma brain stimulation in individuals with AD have also been conducted by Cognito Therapeutics, a company founded by brain researchers in 2016. In early 2021, they shared the promising results from one of their studies at the 2021 AD/PD Conference (an international conference on Alzheimer’s and Parkinson’s diseases and related neurological disorders). That study included a larger number of participants over a longer period than Dr. Singer’s study, and it utilized a strong research methodology (namely, it was a randomized controlled trial with a control group for comparison). 

Seventy-six people with mild-to-moderate AD participated and were randomly assigned to receive either 40 Hz audio-visual stimulation or “sham” stimulation for one hour a day at home, over a six-month period. At the end of the study period, those in the treatment group (compared to those in the sham group) experienced:

·       an average 61% reduction in whole brain atrophy and volumetric loss (which is typically associated with AD); 

·       84% slowing of functional decline, as evidenced by the participants' scores on the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) measure; and

·       83% slowing in memory and cognitive decline, as evidenced by the participants' scores on the Mini-Mental State (or Status) Examination (MMSE).

These findings suggest that this treatment has disease-modifying potential. 

Cognito Therapeutics is continuing to explore the therapeutic effects of this treatment for AD in ever larger studies. Earlier this year, they received a “breakthrough device” designation from the U.S. Food and Drug Administration (FDA), which will help to expedite the clinical development process.

It is possible that this treatment will prove to be effective on its own or in combination with other therapeutics.

As promising as the findings have been so far, there is still much to learn about using gamma brain wave stimulation as a potential treatment for AD. Is 40 Hz the ideal frequency? Is one-hour per day the ideal amount of exposure, and if so, over how many days, weeks, months (perhaps in perpetuity)? Is it possible to over-do gamma wave exposure? What type of device is best for delivering the stimulation? Might the treatment help the brains of healthy people, too (i.e., work as a preventative measure), or help those with neurological conditions other than AD? 

These questions, and many others, still need to be explored. Thankfully, there is much interest and enthusiasm in this innovative approach. Hopefully answers will be available soon to many of the outstanding research questions, and possibly a disease-modifying treatment for AD. In the meantime, researchers warn people not to try improvising with light and/or sound therapies on their own; getting frequencies wrong could make things worse.