A couple of weeks ago, my son sent me a podcast about research into using flashing light to reduce beta amyloid in the brains of laboratory mice. The podcast was from the program Radiolab at WNYC radio in New York. The research used the familiar model of mice whose genes had been edited to cause the brain to form beta amyloids, similar to what occurs in Alzheimer's disease.
The researchers drilled a hole in the skulls of mice and inserted a fiber-optic thread down into the hippocampus. In a way that's not clear to me, they had caused some cells to be light sensitive, and they pulsed light to these cells at a frequency of 40 Hz. After just one hour, they found that forty to fifty percent of the beta amyloid had been removed!
In the new edition of Beating the Dementia Monster, we discuss the role of microglia cells in the brain in removing trash, including tau tangles and beta amyloid accumulation. In older brains, the microglia can become less effective, and this allows the tangles and amyloid plaques to accumulate and complicate brain function. This appears to play a role in the progression of Alzheimer's disease.
The ideas behind the pulsating light is that it re-invigorates one of the rhythms in the brain that, as in a computer, coordinates the activities of different components. The rhythm in question is called gamma, and it seems to regulate the activity of microglia. If age has caused the gamma to falter, this method promises to remedy that. But drilling holes in your head?
The research is being led by Dr. Li-Huei Tsai at MIT's Picower Institute of Learning and Memory. Dr. Tsai is a remarkable neuroscientist who has contributed substantially to many of the issues we have discussed on this blog.
So how does she propose to stimulate the gamma without invading the brain? They put the mice into a room where they pulsed light at 40 Hz and got the same result -- a 50% reduction in beta amyloid.
But are the eyes and fiber-optic cables the only pathway from the outside world into the hippocampus? What about the ears? Dr. Tsai's team used a 40 Hz audio pulse, and got similar results ... with the mice.
An important question is, does this process result in improved cognition? At least in mice, some of Dr. Tsai's tests suggest that it can even recover what might have been lost memories.
Will this work on humans? In research, the record of applying the findings from mouse models to humans is pretty dismal. Mice aren't people, and that's not really Alzheimer's disease in the mice.
Most of the work with mice was conducted in 2016, but clinical trials with humans began in 2019. These are one year trials in which people with early stage Alzheimer's disease are subject to an hour a day of combined visual and auditory stimulation at the magic 40 Hz. Test subjects are evaluated periodically, both for cognition and by MRI. What are the results so far? Dr. Tsai is pretty tight lipped, but she seems to be optimistic.
After the research was initially published, a few entrepreneurs developed devices to deliver 40 Hz light to consumers, and these are available at places like Amazon. The research to support these is still ongoing, but, on the surface, the consumer items seem benign. I would not advise using one, because they are unproven, and there are warnings that they may cause serious problems, especially for people with epilepsy.
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