An early feasibility study finds a potential new treatment for Alzheimer's disease.
For the past few years, Annabelle Singer and her collaborators have been using flickering lights and sound to treat mouse models of Alzheimer's disease, and they've seen some dramatic results.
Now they have results from the first human feasibility study of the flicker treatment, and they're promising.
"We looked at safety, tolerance, and adherence, and several different biological outcomes, and the results were excellent—better than we expected," says Singer, assistant professor in the biomedical engineering department at Georgia Institute of Technology and Emory University.
Singer shared preliminary results of the feasibility study in October at the American Neurological Association annual meeting. Now she is a corresponding author with Emory neurology researcher James Lah of a paper outlining their findings in the journal Alzheimer's & Dementia: Translational Research & Clinical Interventions.
The flicker treatment stimulates gamma waves, manipulating neural activity, recruiting the brain's immune system, and clearing pathogens—in short, waging a successful fight against a progressive disease that still has no cure.
Previous research already had shown that sensory areas in the human brain will entrain to flickering stimuli for seconds to hours. But this was the first time Singer and her team were able to test gamma sensory stimulation over an extended period of time.
The study included 10 patients with Alzheimer's-associated mild cognitive impairment, which required them to wear an experimental visor and headphones that exposed one group to light and sound at 40 hertz for an hour a day over eight weeks, and another group for four weeks after a delayed start.
"We were able to tune the devices to a level of light and sound that was not only tolerable, but it also successfully provoked an underlying brain response," Lah says.
As they hoped and expected, Singer says, "there was widespread entrainment." That is, brain activity—in this case, gamma waves—synchronized to the external stimulation.
Gamma waves are associated with high-level cognitive functions, like perception and memory. Disruptions to these waves have been found in various neurological disorders, not just Alzheimer's.
The human feasibility study showed that the gamma flicker treatment was safe and tolerable. And perhaps most surprising, patients followed the full treatment schedule.
"Adherence was one of our major concerns," Singer says. "When we sent the device home with the participants, would they use it? Would they use it for a couple of days, and that would be it? We were pleasantly surprised that this wasn't the case."
Adherence rates hovered around 90%, with no severe adverse effects reported during the study or the 10-month open label extension (some patients even volunteered to continue being monitored and assessed after the study, though this data wasn't part of the published research).
Some participants reported mild discomfort that could have been flicker related—dizziness, ringing in the ears, and headaches. But overall, Singer says, the device's safety profile was excellent. She also reported some positive biological outcomes.
"We looked at default mode network connectivity, which is basically how different brain regions that are particularly active during wakeful rest and memory, interact with each other," Singer says.
"There are deficits in this network in Alzheimer's, but after eight weeks [of treatment], we found strengthening in that connectivity." This may indicate stronger interactions and therefore better communication between these regions.
In previous animal studies, the 40Hz of flicker stimulated mouse gamma waves, significantly reducing some Alzheimer's pathogenic hallmarks and recruited microglia to the cause—these are the primary immune cells in the brain. But in the human study, there were no clear changes in the presence of pathogens amyloid beta or p-Tau.
However, as with the mouse studies, "we are getting immune engagement in humans," Singer says. The flicker treatment sparked the activity of cytokines, proteins used in cell signaling—a sign that flicker had engaged the brain's immune system.
"That is something we want to see, because microglia do things like clear out pathogens. Some people think that part of what's going wrong in Alzheimer's is a failure of this clearance mechanism," Singer says.
She and Lah have wondered if a longer human trial would make a difference—would there be reduced amyloid activity, for example.
"So far, this is very preliminary, and we're nowhere close to drawing conclusions about the clinical benefit of this treatment," Lah says. "But we now have some very good arguments for a larger, longer study with more people."
Funding for the study came from the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, the Packard Foundation, the Friends and Alumni of Georgia Tech, the Lane Family, the Wright Family, and Cognito Therapeutics. Any findings, conclusions, and recommendations are those of the researchers and not necessarily of the sponsors.
Annabelle Singer owns shares in Cognito Therapeutics, which funded the human study at Emory Brain Health Center. Cognito aims to develop gamma stimulation-related products. These conflicts are managed by Georgia Tech's Office of Research Integrity Assurance.
Source: Georgia Tech
Original Study DOI: 10.1002/trc2.12178
Participants were asked to complete a simple attention task as well as a more challenging "placekeeping" task.
Relying on caffeine to get you through the day isn't always the answer, according to a new study.
The researchers assessed how effective caffeine was in counteracting the negative effects of sleep deprivation on cognition. As it turns out, caffeine can only get you so far.
The study in the most recent edition of Journal of Experimental Psychology: Learning, Memory, & Cognition assessed the impact of caffeine after a night of sleep deprivation.
More than 275 participants were asked to complete a simple attention task as well as a more challenging "placekeeping" task that required completion of tasks in a specific order without skipping or repeating steps.
The study is the first to investigate the effect of caffeine on placekeeping after a period of sleep deprivation.
"We found that sleep deprivation impaired performance on both types of tasks and that having caffeine helped people successfully achieve the easier task. However, it had little effect on performance on the placekeeping task for most participants," says Kimberly Fenn, associate professor of psychology from Michigan State University's Sleep and Learning Lab.
"Caffeine may improve the ability to stay awake and attend to a task, but it doesn't do much to prevent the sort of procedural errors that can cause things like medical mistakes and car accidents," she adds.
Insufficient sleep is pervasive in the United States, a problem that has intensified during the pandemic, Fenn says. Consistently lacking adequate sleep not only affects cognition and alters mood, but can eventually take a toll on immunity.
"Caffeine increases energy, reduces sleepiness, and can even improve mood, but it absolutely does not replace a full night of sleep, Fenn says.
"Although people may feel as if they can combat sleep deprivation with caffeine, their performance on higher-level tasks will likely still be impaired. This is one of the reasons why sleep deprivation can be so dangerous."
Fenn says that the study has the potential to inform both theory and practice.
"If we had found that caffeine significantly reduced procedural errors under conditions of sleep deprivation, this would have broad implications for individuals who must perform high stakes procedures with insufficient sleep, like surgeons, pilots, and police officers," Fenn says. "Instead, our findings underscore the importance of prioritizing sleep."
Source: Michigan State University
Original Study DOI: 10.1037/xlm0001023
U.S. officials suspect a foreign adversary is targeting American personnel with some form of "directed-energy" weapon.
- In recent history, the first reports of a potential directed-energy attack on U.S. personnel came in 2016 from American diplomats working in Cuba.
- There's no "smoking gun" evidence of who's behind the attacks, but some U.S. officials suspect the Russians.
- Supporting that claim is the history of the so-called Moscow Signal, an event in which the Soviets blasted microwaves at the U.S. embassy in Moscow from 1953 to 1976.
Since 2016, more than 130 U.S. government personnel have suffered symptoms linked to Havana syndrome, an acute illness marked by sudden headache, nausea, and the hearing of loud sounds, akin to swarming cicadas. The cause of the illness remains a mystery. But a growing number of U.S. intelligence personnel and researchers fear that some form of "directed-energy" weapon — possibly firing microwave radiation — is to blame.
One of the first cases was reported in Havana, Cuba in 2017. The victim, if it indeed was an attack, was a U.S. Foreign Service officer who was living in a quiet Havana neighborhood among other American personnel. One night she was cleaning her kitchen. If it had been daytime, her kitchen window would have offered a view of a booth outside where Cuban police monitored foreigners like herself.
But at night, the kitchen's interior lights obstructed her view of the booth, The New Yorker reported. As she was cleaning, she suddenly felt a painful burst of pressure inside her head. The pain grew. She had heard rumors of U.S. personnel suffering strange "sonic attacks," and she remembered that a security officer had once advised: to protect yourself, step away from your current position. She did. The pain decreased. But for weeks she suffered headaches, dizziness, and confusion.
Over the past five years, at least 130 U.S. personnel have reported similar symptoms while working in places like China, Russia, and Washington, D.C. The cases vary in severity, but almost all involve sudden headaches and nausea. Some victims may have brain injuries.
A 2019 study published in JAMA found that victims had "significantly smaller" white matter volume and other "significant differences" in brain structure, though it's impossible to determine whether these differences were pre-existing or stem from a directed-energy attack.
What's causing Havana syndrome?
The U.S. hasn't reported a definitive cause of these cases, but intelligence agencies are actively investigating the possibility that bad actors are using some type of directed-energy weapon against U.S. personnel.
A December 2020 report from the National Academies of Sciences found that pulsed radiofrequency energy, which includes microwave radiation, "appears to be the most plausible mechanism in explaining these cases among those that the committee considered." (Other potential causes included infection and chemicals.)
A microwave weapon seems like a fitting culprit. One reason is that sufferers of Havana syndrome often hear loud noises, which is a phenomenon that's known to happen when people are bombarded with high-powered microwaves. In the 1960s, the American neuroscientist Allan H. Frey demonstrated that exposing people to microwaves can make them hear buzzing, clicking, hissing, and speech — even though the microwave device didn't produce any soundwaves. It was all, quite literally, in their heads.
What Americans Heard in Cuba Attacks: The Sound www.youtube.com
How is that possible? Researchers have hypothesized that the noises are induced by thermoelastic expansion of bones and soft tissue in the body: As microwaves strike people, they slightly warm the body, which causes expansion. This expansion might produce sound waves that travel to the ear. Frey and other researchers have proposed different theories about which parts of the body are expanding — those in the head, or those in the ear — but the principle is the same.
To induce auditory effects, a pulsed-microwave weapon needs to transmit 40 joules per square centimeter, according to a U.S. Army report. How much energy is that? Here's how astrophysicist Dr. Ethan Siegel explained it to the American Council on Science and Health (ACSH): "If you are talking about 40 J/cm2 over the entire human body, that's about as much energy as a fully loaded Harley Davidson going 100 mph."
The Moscow Signal
We know such weapons exist, or at least did at one time. During the Cold War, the Soviet Union fired microwaves at the U.S. embassy in Moscow from a nearby apartment building for more than two decades, from 1953 to 1976. The event was dubbed the Moscow Signal.
U.S. intelligence officials initially thought the Soviets were firing the microwaves in an attempt to control the minds of American personnel, but they later reasoned that the Soviets were trying to activate espionage devices inside the building or interfere with the health of the diplomats. To this day, "many questions remain unanswered" about the long-term health effects incurred by Americans who worked at the U.S. embassy in Moscow, according to a 2019 review.
U.S. Embassy in Moscow, RussiaDzerod
A more recent example of an energy-directed weapon is the active denial system, an American technology that uses non-lethal millimeter waves for crowd control. These waves, which the U.S. says are not classified as microwaves, cause a painful heating sensation on the skin. The U.S. is also developing or has developed stronger directed-energy weapons, including microwave weapons that can destroy electronic systems from a distance.
Still, if energy-directed weapons are indeed causing Havana syndrome, what they look like and how they operate remains a mystery.
Who's behind the directed-energy attacks?
There's currently no "smoking gun" evidence for who's responsible for the attacks. But in December 2020, the CIA established a task force to investigate the more than 130 reported cases of Havana syndrome among U.S. personnel. In April, President Joe Biden's administration recently released a statement:
"The White House is working closely with departments and agencies to address unexplained health incidents and ensure the safety and security of Americans serving around the world. Given that we are still evaluating reported incidents and that we need to protect the privacy of individuals reporting incidents, we cannot provide or confirm specific details at this time."
Although the U.S. hasn't officially announced suspects, an anonymous former national security official involved in investigations recently told Politico that Russia is likely behind the attacks. Specifically, the official pointed to Russia's foreign military intelligence agency, commonly called the GRU, whose operatives were present in the locations where American personnel have reported Havana syndrome.
"It looks, smells, and feels like the GRU," said the official. "When you are looking at the landscape, there are very few people who are willing, capable and have the technology. It's pretty simple forensics."
Why Russia would carry out these attacks remains unclear. But the cases have already had a measurable impact on U.S. foreign policy, namely a 50-percent personnel withdrawal from the American embassy in Cuba, a nation that's long been allied with Russia.
U.S. Embassy in CubaU.S. State Department
While U.S. intelligence agencies now seem to be taking these threats seriously, that wasn't always the case. In the first few years after Americans first reported Havana syndrome, some officials were skeptical of the idea that a foreign adversary would launch such brazen attacks, especially on U.S. soil. Some current and former officials say this skepticism has come at the expense of U.S. personnel.
Marc Polymeropoulos, a former CIA officer who was struck by Havana syndrome in a Moscow hotel room in 2017, told the New York Times about a painting created by a fellow CIA officer and Havana syndrome victim. Called "The Gunshot," the painting depicts a red splatter on a black background.
"It signified his feeling that we all wished we had been shot, a visible injury, so that our colleagues would more readily believe us."
Can the main psychoactive ingredient of magic mushrooms help treat the world's sixth most debilitating illness?
- Migraines afflict more than ten percent of the U.S. population, yet treatments are often unreliable and there is no cure.
- The new study involves giving migraine sufferers a placebo and, two weeks later, a single dose of pure synthetic psilocybin.
- The results showed that participants reported significantly fewer migraines in the two weeks after the study.
Psychedelics research is enjoying a renaissance. In recent years, studies have shown that hallucinogenic drugs like LSD, psilocybin, and MDMA seem to have powerful therapeutic effects on conditions including major depression, anxiety, and addiction disorders.
One unique aspect of psychedelics is that taking a single moderate dose can yield long-lasting therapeutic benefits for people with certain conditions, such as cancer patients with depression and anxiety.
Now, new research published in Neurotherapeutics suggests these outsized benefits may also apply to people with migraines. The evidence is preliminary but promising, and it could open up new areas of research for treating migraines, which are often chronic and debilitating.
A painful, debilitating condition
Migraine affects more than 10 percent of the U.S. population and it's ranked as the world's sixth most debilitating illness. Treatments can alleviate migraine symptoms, but efficacy varies from person to person, and even treatments that do work sometimes produce unpleasant side effects. There's currently no cure for the condition.
What's a migraine like?
"Put your finger on your temple and imagine drilling it inside your head," a 29-year-old woman named Heather once told Prevention. "My migraines feel like a screwdriver in there, in that one spot, always on my left side and in my left eye. I get a burning sensation throughout my body and in my jaw. Everything becomes sensitive to the touch, like my muscles are on fire."
Migraine treatments can be either preventive or abortive, and they range from prescription drugs, to over-the-counter medications like Advil Migraine, to home remedies like yoga or taking a hot shower. Psychedelics are another sort of home remedy. For decades, anecdotal evidence has suggested that drugs like LSD and psilocybin may help prevent or alleviate migraines, possibly because they're pharmacologically similar to migraine medications like dihydroergotamine, noted the researchers behind the new study.
To put that anecdotal evidence to the test, the researchers designed a placebo-controlled study in which they gave migraine sufferers a moderate dose of pure synthetic psilocybin. The participants included seven women and three men, all adults, who regularly suffered at least two migraines per week. All participants were free of any serious psychiatric or medical diseases and hadn't abused drugs within three months prior to the study.
To track migraine activity, the participants documented their headache attacks in a journal for six weeks, starting two weeks before the study and stopping two weeks after. The study was divided into two sessions, one of which involved taking a small dose of pure synthetic psilocybin.
"In the first experimental session, all subjects received an oral placebo capsule, and in the second experimental session, all subjects received an identically appearing oral psilocybin capsule," the researchers wrote. "In this design, each subject acted as his own control and placebo was given first so that the potential long-term effects of psilocybin, if given first, would not interfere with placebo treatment, if given second."
Schindler et al.
In the hours after each session, the participants answered questions about any psychedelic effects they might have been experiencing. No participants reported any adverse effects.
In the two weeks after taking the psilocybin, most participants did report significant decreases in migraines compared to baseline and the placebo session.
"The percentages of subjects who had at least 25%, 50%, and 75% reductions in weekly migraine days were as follows: 80%, 50%, 30% after psilocybin, and 20%, 20%, 0% after placebo, respectively," the researchers wrote. "Psilocybin and placebo significantly differed at the level of at least 25% reduction."
Interestingly, these reductions weren't correlated with how strongly the participants felt the psychedelic effects of psilocybin. That suggests migraine sufferers don't need to take a large dose of psilocybin and therefore experience its intense and potentially unpleasant hallucinogenic effects to reap the benefits from it.
But perhaps most promising was that the therapeutic effects lasted at least two weeks after a single dose, differentiating psilocybin from other migraine medications that need to be taken regularly. Still, the researchers noted more research is needed:
"While encouraged by the findings in this exploratory study, before this approach could be used clinically, it is imperative that additional controlled investigations be completed in order to understand psilocybin's full capacity to suppress migraine, as well as its long-term safety and tolerability. To verify the present findings, it will be necessary to replicate the results of this study in a larger sample under a fully randomized design. Studies with a dose range will inform on whether the effects of psilocybin in migraine are dose dependent."
Meconium contains a wealth of information.
- A new study finds that the contents of an infants' first stool, known as meconium, can predict if they'll develop allergies with a high degree of accuracy.
- A metabolically diverse meconium, which indicates the initial food source for the gut microbiota, is associated with fewer allergies.
- The research hints at possible early interventions to prevent or treat allergies just after birth.
The prevalence of allergies arising in childhood has increased over the last 50 years, with 30 percent of the human population now having some kind of atopic disease such as eczema, food allergies, or asthma. The cause of this increase is still subject to debate, though it has been associated with a number of factors, including changes to the gut microbiomes of infants.
A new study by Canadian researchers published in Cell Reports Medicine may shed further light on how these allergies develop in children by examining the contents of their first diaper.
The things you do for science
The research team examined the first stool of 100 infants from the CHILD Cohort Study. The first stool of an infant is a thick, green, horrid-looking substance called meconium. It consists of various things that the infant ingests during the second half of gestation. Additionally, it provides not only a snapshot of what the infant was exposed to during that time, but it also reveals what the food sources will be for the initial gut bacteria that colonize the baby's digestive tract.
The content of the meconium was examined and found to contain such varied elements as amino acids, lipids, carbohydrates, and myriad other substances.
A graph of the comparative, summed abundance of different elements in a metabolic pathway after scaling to median abundance of each metabolite. The blue figures are those children without atopy, the yellow ones show the data for those with an atopic condition. Petersen et al.
The authors fed this information into an algorithm that used this data, along with the identities of the bacteria present as well as the baby's overall health, to predict which infants would go on to develop allergies within one year. The algorithm got it right 76 percent of the time.
A way to prevent childhood allergies?
Infants whose meconium had a less diverse metabolic niche the initial microbes to settle in the gut were at the highest risk of developing allergies a year later. Many of these elements were associated with the presence or absence of different bacterial groups in the digestive system of the child, which play an increasingly appreciated role in our overall health and development. The findings were summarized by senior co-author Dr. Brett Finlay:
"Our analysis revealed that newborns who developed allergic sensitization by one year of age had significantly less 'rich' meconium at birth, compared to those who didn't develop allergic sensitization."
The findings could be used to help understand how allergies form and even how to prevent them. Co-author Dr. Stuart Turvey commented on this possibility:
"We know that children with allergies are at the highest risk of also developing asthma. Now we have an opportunity to identify at-risk infants who could benefit from early interventions before they even begin to show signs and symptoms of allergies or asthma later in life."
A model for early childhood allergies
Petersen et al.
As shown above, the authors constructed a model of how they believe metabolites and bacterial diversity help prevent allergies. Increased diversity of metabolic products in the meconium encourage the development of "healthy" families of bacteria, like Peptostreptococcaceae, which in turn promote the development of a healthy and diverse gut microbiome. Ultimately, such diversity decreases the likelihood that a child will develop allergies.