It sounds almost too simple to be true: Put on a pair of rattling headphones with special flickering glasses for an hour a day to prevent dementia. A number of clinical studies are currently testing whether optical and acoustic stimulation in the frequency range of gamma waves can delay, improve or even prevent dementia.
The studies indicate that stimulation at 40 Hertz (Hz) – i.e. 40 pulses per second – stimulates a kind of tissue cleansing in the brain, including the disposal of harmful metabolic products. Some researchers claim that this can also remove the deposits from the brain that are considered to be the cause of the most common form of dementia: Alzheimer’s disease.
A US research team recently reported in the journal “Nature” what exactly happens after conducting experiments on mice. Roughly speaking, the gamma waves ensure that a lot of fluid circulates between the nerve cells in the brain and flushes out protein clumps typical of Alzheimer’s. The President of the German Society for Neurology, Lars Timmermann, speaks of “fascinating insights”. “These studies open up new insights,” says the head of the Department of Neurology at Marburg University Hospital.
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It remains to be seen whether the activation of brain cells in the gamma frequency range also has therapeutic potential. One thing is clear: effective prevention would be a gold mine for the provider. “The topic is extremely attractive,” says Wolf Singer, long-time director at the Frankfurt Max Planck Institute for Brain Research and a key player in the discovery of gamma waves. “The whole world is talking about Alzheimer’s.”
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No wonder: In Germany alone, this most common form of dementia affects around a million people, and the number is rising. The cause has not yet been precisely clarified. The main suspicion, however, is directed against the protein fragment beta-amyloid (Aß), which accumulates between nerve cells in the brain.
The antibody lecanemab came onto the market in the USA a little over a year ago. It is intended to remove these Aß plaques and, according to studies, moderately slows down the progression of the disease in the early stages. It could soon also be approved in the EU – but is accompanied by considerable side effects such as cerebral edema and microbleeds.
Light stimulates brain flushing
Perhaps stimulation with gamma waves could also clear Aß – but in a different way. These sensory stimuli are intended to cause nerve cells to vibrate in the gamma wave range and thus start the cleansing process. Timmermann sees a parallel to cognitive processes: “In certain brain activities, we see activity of neuron groups in the range of 40 Hz,” he says, pointing to language learning, image recognition or decision-making processes as examples.
What happens in the brain during 40 Hz stimulation was described in the 2016 study by the team led by Li-Huei Tsai from the Massachusetts Institute of Technology (MIT) in the journal “Nature”. The brain researcher co-founded the company Cognito Therapeutics, which is currently conducting various studies to determine whether synchronized opto-acoustic stimulation – with the specially developed “Spectris” headset – can help people with mild to moderate Alzheimer’s symptoms.
In the current study, the team writes that in special genetically modified “Alzheimer’s mice”, opto-acoustic stimulation at 40 Hz increases neuronal activity and at the same time reduces Aβ concentrations in the brain. The so-called glymphatic system is responsible for this: The fairly new term combines the lymphatic system – which cleans tissue outside the brain – with the glial cells, which are said to be significantly involved in this in the brain.
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According to the study, the stimulation ensures that a particularly large amount of fluid circulates through the tissue in the mice’s brains. This nerve water transports the Aß between the cells in the brain. “The cell groups are flushed better and the waste between the cells is removed,” explains neurologist Timmermann, who was not involved in the work. “That’s fascinating.”
Outside the brain, the team found an increased diameter in the lymphatic vessels that drain the cerebrospinal fluid, which suggests increased drainage. And last but not least: the adjacent lymph nodes contained increased amounts of beta-amyloid.
The bottleneck for memory processes
As fascinating as these processes are in mice, it remains to be seen whether they stop or delay the progression of Alzheimer’s disease in humans. The Frankfurt expert Singer, for example, is “cautiously skeptical”. Ultimately, the success of the therapy depends on the gamma waves reaching more than just the sensory areas in the brain. “With the combination of optical and acoustic stimuli, we want to force as many brain regions as possible into this rhythm,” says Singer.
This may work for the cortex, but an important target is the deeper area that is largely responsible for memory: the hippocampus. “The hippocampus is the bottleneck for memory processes,” says Thomas Gasser from the University Hospital of Tübingen. “It is questionable whether the gamma waves also reach this area of the brain.”
And even if the stimulation succeeds, there is still another problem: the first symptoms of Alzheimer’s disease are preceded by a gradual process lasting years or decades in which nerve cells die in a chain reaction. “You would have to do this early on to stop this cascade,” says Gasser.
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A dozen studies are currently testing the potential of the approach on people – there are no results yet. Most of the investigations are scheduled to end during 2025, after which the evaluation will follow. “We need observation periods of at least two, preferably five to ten years, to be able to say whether there is a therapeutic effect or not,” says Timmermann. “It will take another decade before we know for sure whether and which form of intervention could be helpful and which not.”
After all: According to studies, gamma wave treatment is considered safe. “We assume that this stimulation does not damage the healthy brain,” says Timmermann. In contrast, antibodies such as Lecanemab, which is about to be approved in the EU, are not only very expensive, but are also sometimes associated with serious side effects. In comparison, putting on headphones and special glasses at home for an hour a day seems rather gentle – if it is of any use.