First human trials test light & sound therapy for Alzheimer's disease
A new study published in the journal PLoS ONE has reported on the first human tests of an experimental therapy using sound and light to treat Alzheimer's disease (AD). The initial findings are promising, with the unique treatment leading to some neurological and cognitive improvements, but the small trial size means more study is needed before anyone can say this type of therapy works.
Over the last seven years, Li-Huei Tsai and colleagues at MIT's Picower Institute for Learning and Memory have been investigating an unusual hypothesis. The researchers found toxic proteins associated with Alzheimer's disease could be eliminated from mouse brains following exposure to flickering lights. Further research found the magic frequency was 40 Hz. When animals were exposed to both sound and light at that frequency, improvements in brain health were detected.
Of course, these kinds of animal tests don't mean much if they can't be replicated in humans, so after further investigations revealed how this sensory therapy could be affecting a mouse brain, the researchers started preliminary human experiments. Working with colleagues at Massachusetts General Hospital, two clinical trials set out to test the therapy in humans.
The first Phase 1 study recruited 43 participants to test whether this kind of light and sound exposure was safe, and did anything to the human brain. Each subject was monitored using EEG measures while experiencing a short exposure to what has been dubbed by the researchers as GENUS (Gamma ENtrainment Using Sensory stimulation).
This preliminary study comprised both healthy and cognitively impaired subjects, as well as participants with epilepsy in order to evaluate the seizure potential of the treatment. After a short exposure to the sensory stimulation, the researchers found a number of brain regions synchronize with the 40-Hz frequency.
"Our Phase 1 study demonstrated that 40-Hz GENUS using synchronized light and sound can effectively induce gamma entrainment across multiple brain regions in cognitively normal individuals, patients with medically intractable epilepsy, and in patients with mild AD dementia," the researchers write in the new study. "We are the first to show that GENUS light and sound stimulation entrains not only cortical sensory regions, but also distant cortical and subcortical regions such as the gyrus rectus, the amygdala, the hippocampus, and, in particular, the insula."
The second trial recruited 15 participants with early-stage Alzheimer's disease. Each participant was given a device to take home and use for around an hour a day. The device was essentially a small LED white board with an iPad in the middle and a soundbar underneath.
While watching videos on the iPad, the LED light panel on the white board would flicker at a rate of 40 Hz and the soundbar would play a 40-Hz tone. Half the cohort was randomized to a sham control condition, exposed to a constant white light and white noise.
Compliance was relatively high between both the GENUS and the sham groups, with participants completing the daily requirement of exposure around 90 percent of the time. After around three months of use the researchers could detect statistically significant differences between the two groups, both on brain imaging and memory tests.
"We found that, relative to the control group, the active group that had daily usage of 40Hz GENUS over three months had less brain atrophy and reduced loss of functional connectivity, improved markers of sleep, and improved performance on an associative memory task," the researchers explained in the study.
Tsai is cautious not to overstate these initial findings. It's early days for human studies, she noted, larger cohorts of patients are needed to better understand the impacts of this sensory stimulation and longer trials will hopefully establish more prominent beneficial effects.
“While we are also encouraged to see some significant positive effects on the brain and behavior, we are interpreting them cautiously, given our study’s small sample size and brief duration," added Tsai. "These results are not sufficient evidence of efficacy, but we believe they clearly support proceeding with more extensive study of 40-hertz sensory stimulation as a potential noninvasive therapeutic for Alzheimer’s disease.”
Tsai and colleague Ed Boyden have already founded a company called Cognito Therapeutics to conduct further clinical research on the technology. A larger clinical trial testing the sensory stimulation therapy in several hundred mild-to-moderate Alzheimer's patients is now underway. That trial will explore the effects of daily hour-long treatments for up to one year.
The new study was published in PLoS ONE.