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An Hour of Light and Sound a Day Might Keep Alzheimer’s at Bay

Angus Chen - Scientific American March 14, 2019 (Publication)
This is an summary article about the work of Shannon Macauley, a neuroscientist at Wake Forest School of Medicine who found that light and sound has a siginicant impact on the Alzheimer's
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There is no cure for Alzheimer’s disease. Although a few drugs manage temporarily certain cognitive symptoms of the illness, none can stop or meaningfully slow its progression. “We really don’t have much to offer people,” says Shannon Macauley, a neuroscientist at Wake Forest School of Medicine. Virtually all new treatments have failed in clinical trials. But new research is looking beyond drugs to see what relief might come from a simple LED light and a speaker. Bathing patients in flashing light and pulsing sounds both tuned to a frequency of 40 hertz might reverse key signs of Alzheimer’s in the brain, according to a paper published in Cell on Thursday. “I think it’s an absolutely fascinating paper to be honest,” says Macauley, who was not involved in this work. “It’s a very provocative idea. It’s noninvasive and easy and low cost, potentially, so if it were to come to fruition in humans—that’s fabulous.” Still, all this is a big if, Macauley acknowledges. The work was done in mice with genetic alterations that doomed them to develop key symptoms and pathology of Alzheimer’s disease. One batch of mice formed neurofibrillary tangles inside their neurons—dysfunctional knots of a protein called tau that can lead to the cell’s death. Another batch of the mice developed amyloid beta plaques—sticky heaps of protein that dam the flow of communication between neurons. All the mice also had a third hallmark of the disease—irregular brain activity in the gamma range of brain waves that oscillate between 30 and 100 times a second. In 2015 neuroscientist Li-Huei Tsai, director at The Picower Institute for Learning and Memory at Massachusetts Institute of Technology, was working on an experiment to manipulate that brain activity by flashing a white light at these mice. Like light strobes, our brains flicker. Brain waves are generated when large groups of neurons oscillate on and off together. Neurons encode our thoughts and actions and senses in this rhythmic electrical flutter. So when Tsai tuned her light to flash 40 times a second, or 40 hertz, and flickered it at the mice, their brains flickered back—generating gamma waves at a corresponding 40 hertz. Then, something unexpected happened. When Tsai dissected the mice brains afterward, the amount of amyloid plaques and tau tangles in the mice that saw the light had plummeted. “It was the most remarkable thing,” Tsai says. “The light flicker stimulation triggers a tremendous microglia response. These are the brain’s immune cells that clear cell debris and toxic waste including amyloid. They’re impaired in Alzheimer’s disease, but [the light] seems to restore their abilities.” When Tsai dissected the mice brains afterward, the amount of amyloid plaques and tau tangles in the mice that saw the light had plummeted. “It was the most remarkable thing,” Tsai says. “The light flicker stimulation triggers a tremendous microglia response. These are the brain’s immune cells that clear cell debris and toxic waste including amyloid. They’re impaired in Alzheimer’s disease, but [the light] seems to restore their abilities.” This clearing-out process only happened in the visual cortex where the brain processes light information. To get these effects to penetrate deeper into the brain, she added a clicking sound like a dolphin’s chirrup that also had a 40-hertz frequency. When the mice sat in a room with both the flashing light and the droning sound for an hour day, seven days in a row, amyloid plaques and tau tangles began falling in not just the audio and visual cortices but the prefrontal cortex and the hippocampus as well. “This was one of the big jumps in the new paper,” Macauley says. “These are the learning and memory centers of the brain. And there was about a 40 or 50 percent decrease in amyloid and tau levels. It’s an absolutely impressive feat.” That showed when Tsai put the mice through a set of cognitive tests. In one, where the mice were given a familiar and an unfamiliar object to explore, mice that didn’t get the treatment acted as though they’d never seen the familiar object. “That shows some memory problems,” Tsai says. Mice that saw the light and heard the sound spent about two thirds of the time that untreated mice did examining the familiar object. “It was unbelievable,” Tsai says. “This is the first time we’ve seen that this noninvasive stimulation can improve cognitive function. It’s not a drug or an antibody or anything, it’s just light and sound.” One possible explanation for this is brains with Alzheimer’s have irregular, often hyperactive, neurons, says Jorge Palop, a neurologist at the University of California, San Francisco, who did not work on the study. By providing the brains with a steady and regular beat, the repeating light and sound might work as a kind of metronome for brain activity. “This could be like resetting the mice every day and correcting some of this abnormal activity that they have,” he says. “Then downstream of that are all these beneficial effects.” All of this is still at the level of speculation. Researchers simply do not know why these brain waves, specifically ones rising from light and sound stimulation at 40 hertz and no other frequencies, can lead to a reversal of Alzheimer’s disease symptoms. “That’s a mystery,” says Terrence Town, a neuroscientist, at the University of Southern California who was not involved with the work. It’s also not clear if these beneficial effects would appear or if 40 hertz is the “magic” frequency in humans, he says. Tsai is already working on answering those questions. In human studies underway at Cognito Therapeutics, a start-up she founded with her colleague Ed Boyden, she says light and sound seem to increase gamma waves in healthy participants without negative side effects. “Nobody gets sick or even complains about it,” Tsai says. “But to see a [therapeutic] effect in humans, you’ll have to wait a long time. If this approach has an impact, the experiment could easily take five years to have some conclusive answer.”

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Photobiomodulation: Lasers vs Light Emitting Diodes?

Vladimir Heiskanen and Michael R. Hamblin - Photochem Photobiol Sci. Author manuscript; available in PMC 2019 Aug 8. (Publication)
This is one of the most detailed summary articles discusses the LEDs versus Laser for therapy.
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Distinct wavelengths of light have been known to have various biological effects on humans. Ultraviolet-B radiation promotes vitamin D synthesis and visible light has important effects on circadian rhythm entrainment and alertness. For more than three thousand years, sunlight has been used as a medical treatment for a variety of diseases by the ancient Egyptians, Indian Ayurveda and traditional Chinese medicine, but it is only since the invention of the electric light in the latter part of the 19th century, that an alternative has emerged. Since the beginning of the 21st century, over 2000 PubMed-indexed scientific articles have also been published focusing on the various physiological effects of red light and near-infrared radiation. These wavelengths of light have been shown to penetrate through human tissues and to locally (and possibly systemically) affect cellular metabolism, cellular signaling, inflammatory processes and growth factor production. This treatment is nowadays called “photobiomodulation therapy” (PBM), but it has also had more than 60 other names in the scientific literature; “low-level laser therapy” (LLLT) has been the most commonly used term. The reasons to prefer the use of “PBM” over “LLLT” are twofold [1]. Firstly PBM does not imply that a laser is necessary for the therapeutic benefits to occur. Secondly PBM implies that the therapeutic effects could in some circumstances be due to inhibition effects, as well as to the more usual stimulation effects. Table 1 illustrates various medical conditions (or their animal models), for which PBM has already been investigated, in animals and/or clinical human studies. These indications include a multitude of diseases of brain, bone, eyes, internal organs, connective tissue, skin and muscles. Most of the published results have been positive. More than 40 clinical studies are currently underway based on information currently available in the database. Photobiomodulation (PBM) is a treatment method based on research findings showing that irradiation with certain wavelengths of red or near-infrared light has been shown to produce a range of physiological effects in cells, tissues, animals and humans. Scientific research into PBM was initially started in the late 1960s by utilizing the newly invented (1960) lasers, and the therapy rapidly became known as ‘low-level laser therapy”. It was mainly used for wound healing and reduction of pain and inflammation. Despite other light sources being available during the first 40 years of PBM research, lasers remained by far the most commonly employed device, and in fact, some authors insisted that lasers were essential to the therapeutic benefit. Collimated, coherent, highly monochromatic beams with the possibility of high power densities were considered preferable. However in recent years, non-coherent light sources such as light-emitting diodes (LEDs) and broad-band lamps have become common. Advantages of LEDs include no laser safety considerations, ease of home use, ability to irradiate a large area of tissue at once, possibility of wearable devices, and much lower cost per mW. LED photobiomodulation is here to stay. Keywords: photobiomodulation therapy, low-level laser (light) therapy, light emitting diodes, mechanisms: medical indications.
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Home Search Introduction

Ken Teegardin - (Website)
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This tool is a searchable collection of technical publications, books, videos and other resources about the use of lasers and light for PhotoBioModulation (PBM). Enter a keyword above or see some of our favorite queries below. 

Here are some of our favorite queries:


All the resources include links to the original source so we are not making any statement about the use of lasers for treating non-FDA cleared application, we are simple summarizing what others have said.

Where every possible, we have included a link to the orginal publication.

This tool uses a broad match query so:

  • It does not correct spelling and searches only cold laser related subjects so do not use LLLT, cold or laser in the search bar
  • It works better with shorter search terms or even parts of search terms
  • It searches all the available fields so you can enter a body part, author, condition or laser brand.
  • Where ever possible, the detailed section about the resource will link to the sources.
  • This system is only for photobiomodulation or cold laser therapy research (including LLLT, laser acupuncture and high power laser therapy) only. It does NOT include photodynamic laser therapy (where the laser is used to react with a pharmaceutical), hot surgery lasers or cosmetic lasers. It does include some resources on weight loss and smoking cessation.

The results of the search are sorted based on 3 quality factors on a scale of 1 to 10 with 10 being the best score. Originally all the resources were given a 5-5-5 until they could be individually evaluated. These scores are purely opinion and are only used to simplify the rank of the results from more valuable to least valuable. This should not be considered a critique of any work. This system was created to help researchers (including ourselves) find the most usable resources for any cold laser therapy research. The resources are assigned values based on the following 3 factors:

  • Efficacy: The resource (especially research papers) should show a significant improvement in the condition being treated. Resources that show better results are given a higher quality score.
  • Detail: The source must give enough information that the results can be duplicated. If a resource lacks too many details that it cannot be recreated, it is given a lower detail score.
  • Lack of Bias: Many resources are created to try and show that one device is superior to its competition. Many manufacturers have staff that crank out biased papers on a regular basis on the hope that this will make their product look superior. If the author of the resource is paid by a manufacturer of the resource appears to be biased towards one device and not one technology, the resource has much less value.

Over the past few years of working with research, we found that a majority of the published resources are lacking in one of these three ranking factors.
The original goal of this research tool was to tie published resources to the protocols in the library. This connection allows users to trace each protocol back to a list of resources so the protocol can be researched and improved.

General Comments

When many of the first research papers were published, the most power laser available for therapy were less than 100mW and many systems had to be pulsed to keep the laser from burning out too quickly. Today, system are available that will deliver up to 60,000mW of continuous output. Because of these power limitation, many early studies were limited to extremely low dosages by today’s standards. It takes a 50mW system 17 minutes to deliver 50 joules at the surface of the skin. If this was spread over a large area of damage or was treating a deeper problem, the actual dosages were much less than 1J/cm2.  Today, we know that these dosages typically produce very little or no results.
About 80% of the resources in this database are in the near infrared wavelength. There is also some interest in the red wavelength (600 to 660nm) . Other wavelengths like blue, purple, and green have very little scientific research behind them and have not gotten much traction in the core therapy market with the exception of some fringe consumer products.
Legal Disclaimer
This research tool is free to use but we make no claims about the accuracy of the information. It is an aggregation of existing published resources and it is up to the user to determine if the source of the resources has any value. The information provided through this web site should not be used for diagnosing or treating a health problem or disease. If you have or suspect you may have a health problem, you should consult your local health care provider.

The query result(s) can be shared using the following direct link. Anyone who clicks on this link in an email or on a web site will be shown the current results for the query.