Dementia: How to Decrease Dementia? How to Fight Dementia?
Thank you to a dear patient you told me about these latest finding in the field of Dementia.
A couple of days, a doctor friend of mine told me about her dad who has Alzheimer’s and how the following helped.
1.see this MD at Johns Hopkins who is into brain training
2.She saw a “huge turn around” when her dad started playing ping pong every day.
3. They checked his LCAT food sensitives test for general health & Homocysteine levels
4.Treatment: High does of Omega 3
5. Started giving: Methelated Folate
Plan:
1. Daily/weekly ping pong at Potomac Community Center
2. Brain training with Dr. Fotuhi highly.
3. All of above.
4. And maybe soon we will recommend patients look at high frequency flashing Christmas lights at 40 beats per second which is Gamma frequency.
Toward Treating Alzheimer’s Disease with Brain Waves
In a mouse model, researchers mitigated three Alzheimer’s disease–associated symptoms by stimulating gamma waves with light.
| December 7, 2016
PICOWER INSTITUTE FOR LEARNING AND MEMORYWhen brain cells fire rhythmically and in sync, they produce waves, which are categorized by their firing frequencies. Delta waves (1.5 Hz to 4 Hz), for example, are produced during deep sleep, theta waves (4 Hz to 12 Hz) occur during running and deep meditation, and gamma waves (25 Hz to 100 Hz) are associated with excitement and concentration. Disruption of gamma waves could be a key contributor to Alzheimer’s disease pathology, according to a mouse study published today (December 7) in Nature. And the restoration of these waves, researchers propose, may one day be an option for Alzheimer’s disease treatment.
MIT’s Li-Huei Tsai, Ed Boyden, and their colleagues have shown that stimulating neurons to produce gamma waves at a frequency of 40 Hz reduces the occurrence and severity of several Alzheimer’s-associated symptoms in a mouse model of the disease. The researchers induced slow gamma waves using optogenetics, and by exposing the mice to flickering light—an approach they suggest could translate to human therapies.
“It’s a pretty striking result that at one particular frequency with which they entrained the brain . . . they were able to reduce, in the mouse at least, all three hallmarks of Alzheimer’s pathology,” said Rudolph Tanzi, who leads genetics and aging research at Massachusetts General Hospital and was not involved in the work.
Stimulation of gamma waves reduced levels of amyloid-β, decreased phosphorylation of tau, and led the brain’s immune cells—microglia—to perform their usual housekeeping role, clearing away cellular debris, including amyloid-β (as opposed mounting an inflammatory response as microglia do in Alzheimer’s disease, Tanzi explained).
The results are “important both for mechanistic study and also for potentially therapeutic developments,” said Yadong Huang of the University of California, San Francisco, and the Gladstone Institute of Neurological Disease, who also was not involved in the work. The study suggests that “a slow-gamma deficit might be part of this [Alzheimer’s disease] pathogenesis [and that] manipulating slow-gamma activity . . . could be a new way to suppress amyloid-β production and increase amyloid-β clearance,” Huang added. Scientists have long hypothesized that decreasing amyloid-β accumulation could help reverse—or even prevent—symptoms of Alzheimer’s disease.
Huang and colleagues previously reported that, during sharp-wave ripples in the hippocampus, patterns of brain activity thought to occur during memory replay and consolidation, gamma waves were disrupted in a mouse model of Alzheimer’s disease. Gamma waves are also disrupted in the brains of people with Alzheimer’s disease. But exactly how gamma waves contribute to this neurodegenerative pathology remains unclear.
To learn more, Tsai and Boyden first examined gamma waves in the hippocampi of Alzheimer’s disease–model mice. Compared with those of control animals, the hippocampi of the model mice had fewer gamma waves during sharp-wave ripples, but gamma waves during theta waves were unaffected.
Next, the researchers optogenetically stimulated hippocampal neurons to produce gamma waves in Alzheimer’s disease–model mice that had transgenically received both a light-responsive ion channel and a fluorescent label in their hippocampal neurons. Compared with control animals (model mice that were stimulated at stochastic frequencies or mice stimulated at 40 Hz that received the fluorescent label but not the ion channel), the gamma-stimulated mice had lower hippocampal levels of amyloid-β. Further experiments revealed that the mice that underwent gamma stimulation had reduced amyloid-β production. Additionally, gamma stimulation led microglia to shift toward their housekeeping function and engulf amyloid-β. The resulting amyloid-β reductions in gamma-stimulated animals were likely due both to lower production of the protein and to microglia clearing more of it away, the authors wrote.
“Optogenetics is very precise and therefore a good way to study how cell types and oscillations can be used in potential therapeutic prototyping,” Boyden said during a press briefing this week (December 6). However the procedure, as performed on mice, involves drilling a hole in the skull and injecting a transgene-delivering virus into the brain. “When it came time to think about how we could translate this to humans, we started thinking about non-invasive strategies to achieve this result,” said Boyden.
Their solution? Flickers of visible light—“like a strobe light, but faster,” coauthor Annabelle Singer of Georgia Tech and Emory University said during the press conference—to stimulate not the hippocampus but the visual cortex.
After an hour of stimulation by an LED light flickering at 40 Hz to induce gamma waves, Alzheimer’s disease–model mice had lower levels of amyloid-β than control model mice that were kept in the dark. The researchers repeated the experimental treatment, in older mice that had developed amyloid plaques, finding that the treatment—this time for an hour each day and for seven days—also led to plaque reduction. Finally, in a mouse model of tauopathy, mice subjected to the flickering-light treatment had lower levels of tau phosphorylation associated with formation of neurotoxic tangles.
It remains to be seen, however, whether gamma stimulation can prevent memory loss or rescue learning and memory deficits, Huang noted.
Going forward, Tsai and colleagues hope to develop a technology based on this flickering-light treatment to treat Alzheimer’s disease patients.
Tanzi has already developed goggles that flash light at other frequencies in order to stimulate other kinds of brain waves—such as the theta waves that can occur during meditation. “We invented this so that people could relax. The glasses are used recreationally,” Tanzi said. “In the future, you could think about how this type of thing could be used to flicker at gamma to get these beneficial effects that they saw in the current study.”
Tsai and some of her coauthors have started a company, Cognito Therapeutics, to develop treatments for Alzheimer’s disease, including technologies based on gamma stimulation via flickering light.
“While this is promising, we have many steps to go to translate these discoveries from mice into a therapy for humans using this noninvasive technique,” Singer said during the press conference. “We need to do clinical studies in humans, and we’re currently working hard to do that.”
H. Iaccarino et al., “Gamma frequency entrainment attenuates amyloid load and modifies microglia,” Nature, doi:10.1038/nature20587.
http://www.radiolab.org/story/bringing-gamma-back/
Strobe lighting provides a flicker of hope in the fight against Alzheimer’s
Exposure to flashing lights stimulates brain’s immune cells to clean up toxic proteins causing the disease, study finds
Strobe lighting has been shown to reduce levels of the toxic proteins seen in Alzheimer’s disease, in findings that raise the tantalising possibility of future non-invasive treatments for the disease.
The study, in mice, found that exposure to flickering light stimulated brain waves, called gamma oscillations, that are known to be disturbed in Alzheimer’s patients. Boosting this synchronous brain activity appeared to act as a cue for the brain’s immune cells, prompting them to absorb the sticky amyloid proteins that are the most visible hallmarks of the disease in the brain’s of people with Alzheimer’s.
The authors caution that a “big if” remains over whether the findings would be replicated in humans – and whether cognitive deficits as well as visible symptoms of the disease would be improved.
“If humans behave similarly to mice in response to this treatment, I would say the potential is just enormous, because it’s so non-invasive, and it’s so accessible,” said Li-Huei Tsai, director of the Picower Institute for Learning and Memory at MIT, and the paper’s senior author.
Alzheimer’s research has faced a number of major setbacks – most recently the failure of Eli Lily’s drug trial – after promising results in rodents did not translate into clinical improvements for patients.
The latest intervention, scientists predict, should be quicker and cheaper to confirm in humans than pharmaceuticals, which typically take more than a decade to develop and assess for safety before the clinical efficacy is even examined.
The study, published on Wednesday in the journal Nature, hinges on the observation that Alzheimer’s patients show a loss of synchronised brain activity, known as gamma oscillations, which is linked to attention and memory.
To restore the activity, the scientists first used mice that had been genetically engineered such that the neurons that generate gamma activity in the brain were sensitive to light. The technique, known as optogenetics, allowed the scientists to artificially cause groups of neurons to fire in unison by pulsing light into the brains of the mice.
After an hour of stimulation, the researchers found a roughly 50% reduction in the levels of beta amyloid proteins in the hippocampus, the brain’s memory centre. Closer inspection showed that the amyloid had been taken up by microglia, the brain’s immune cells.
In a healthy brain, microglia act as chemical rubbish collectors, surveying the local environment, clearing up unwanted compounds, but in Alzheimer’s these cells can lose this function and switch into an inflammatory state in which they secrete toxic compounds instead. Strengthening gamma oscillations appeared to switch the microglia back into a productive state.
Next, the scientist showed that gamma oscillations could also be stimulated non-invasively in the visual brain region simply by exposing the mice to a flickering light. At 40Hz the flicker of the light is barely discernible and would be “not offensive at all” for a person to have in the background.
After being given one hour of flickering light each day for a week, the scientists saw a 60% reduction of harmful amyloid plaques in the brains of the mice.
Ed Mann, an associate professor of neuroscience at the University of Oxford, said: “I was surprised, and it’s exciting, that such a simple stimulus can target a molecular pathway and have such an effect in an hour.”
Questions remain, however, about whether boosting gamma oscillations and sweeping amyloid plaques out of the visual brain region would help with memory, which is centred in the hippocampus, or broader cognitive abilities.
David Reynolds, chief scientific officer at Alzheimer’s Research UK, said: “It is conceivable that changing brain cell rhythms could be a future target for therapies, but researchers will need to explore how light flickering approaches could not only reduce amyloid in the visual area of the brain but in those areas more commonly affected in Alzheimer’s.”
The authors suggest that it may be possible to take a multi-sensory approach, using a combination of flashing lights and vibrating chairs. Tsai and Ed Boyden, a colleague at MIT and co-author, have started a company called Cognito Therapeutics to pursue tests in humans.
There are 850,000 people with dementia in Britain and this figure is expected to reach 1 million by 2025. Earlier this year, dementia overtook heart disease as the leading cause of death in England and Wales.