Scientists Are Harnessing Sound Waves in Hopes of Treating Alzheimer’s
In 2010, a 67-year-old former executive assistant for a Fortune 500 company was diagnosed with mild cognitive impairment. By 2014, her doctors confirmed she had Alzheimer's disease.
As her disease progressed, she continued to live independently but wasn't able to drive anymore. Today, she can manage most of her everyday tasks, but her two daughters are considering a live-in caregiver. Despite her condition, the woman may represent a beacon of hope for the approximately 44 million people worldwide living with Alzheimer's disease. The now 74-year-old is among a small cadre of Alzheimer's patients who have undergone an experimental ultrasound procedure aimed at slowing cognitive decline.
In November 2020, Elisa Konofagou, a professor of biomedical engineering and director of the Ultrasound and Elasticity Imaging Laboratory at Columbia University, and her team used ultrasound to noninvasively open the woman's blood-brain barrier. This barrier is a highly selective membrane of cells that prevents toxins and pathogens from entering the brain while allowing vital nutrients to pass through. This regulatory function means the blood-brain barrier filters out most drugs, making treating Alzheimer's and other brain diseases a challenge.
Ultrasound uses high-frequency sound waves to produce live images from the inside of the human body. But scientists think it could also be used to boost the effectiveness of Alzheimer's drugs, or potentially even improve brain function in dementia patients without the use of drugs.
The procedure, which involves a portable ultrasound system, is the culmination of 17 years of lab work. As part of a small clinical trial, scientists positioned a sensor transmitting ultrasound waves on top of the woman's head while she sat in a chair. The sensor sends ultrasound pulses throughout the target region. Meanwhile, investigators intravenously infused microbubbles into the woman to boost the effects of the ultrasound. Three days after the procedure, scientists scanned her brain so that they could measure the effects of the treatments. Five months later, they took more images of her brain to see if the effects of the treatment lasted.
Promising Signs
After the first brain scan, Konofagou and her team found that amyloid-beta, the protein that clumps together in the brains of Alzheimer's patients and disrupts cell function, had declined by 14%. At the woman's second scan, amyloid levels were still lower than before the experimental treatment, but only by 10% this time. Konofagou thinks repeat ultrasound treatments given early on in the development of Alzheimer's may have the best chance at keeping amyloid plaques at bay.
This reduction in amyloid appeared to halt the woman's cognitive decline, at least temporarily. Following the ultrasound treatment, the woman took a 30-point test used to measure cognitive impairment in Alzheimer's. Her score — 22, indicating mild cognitive impairment — remained the same as before the intervention. Konofagou says this was actually a good sign.
"Typically, every six months an Alzheimer's patient scores two to three points lower, so this is highly encouraging," she says.
Konofagou speculates that the results might have been even more impressive had they applied the ultrasound on a larger section of the brain at a higher frequency. The selected site was just 4 cubic centimeters. Current safety protocols set by the U.S. Food and Drug Administration stipulate that investigators conducting such trials only treat one brain region with the lowest pressure possible.
The Columbia trial is aided by microbubble technology. During the procedure, investigators infused tiny, gas-filled spheres into the woman's veins to enhance the ultrasound reflection of the sound waves.
The big promise of ultrasound is that it could eventually make drugs for Alzheimer's obsolete.
"Ultrasound with microbubbles wakes up immune cells that go on to discard amyloid-beta," Konofagou says. "In this way, we can recover the function of brain neurons, which are destroyed by Alzheimer's in a sort of domino effect." What's more, a drug delivered alongside ultrasound can penetrate the brain at a dose up to 10 times higher.
Costas Arvanitis, an assistant professor at Georgia Institute of Technology who studies ultrasonic biophysics and isn't involved in the Columbia trial, is excited about the research. "First, by applying ultrasound you can make larger drugs — picture an antibody — available to the brain," he says. Then, you can use ultrasound to improve the therapeutic index, or the ratio of the effectiveness of a drug versus the ratio of adverse effects. "Some drugs might be effective but because we have to provide them in high doses to see significant responses they tend to come with side effects. By improving locally the concentration of a drug, you open up the possibility to reduce the dose."
The Columbia trial will enroll just six patients and is designed to test the feasibility and safety of the approach, not its efficacy. Still, Arvantis is hopeful about the potential benefits of the technique. "The technology has already been demonstrated to be safe, its components are now tuned to the needs of this specific application, and it's safe to say it's only a matter of time before we are able to develop personalized treatments," he says.
Konofagou and her colleagues recently presented their findings at the 20th Annual International Symposium for Therapeutic Ultrasound and intend to publish them in a scientific journal later this year. They plan to recruit more participants for larger trials, which will determine how effective the therapy is at improving memory and brain function in Alzheimer's patients. They're also in talks with pharmaceutical companies about ways to use their therapeutic approach to improve current drugs or even "create new drugs," says Konofagou.
A New Treatment Approach
On June 7, the FDA approved the first Alzheimer's disease drug in nearly two decades. Aducanumab, a drug developed by Biogen, is an antibody designed to targetand reduce amyloid plaques. The drug has already sparked immense enthusiasm — and controversy. Proponents say the drug is a much-needed start in the fight against the disease, but others argue that the drug doesn't substantially improve cognition. They say the approval could open the door to the FDA greenlighting more Alzheimer's drugs that don't have a clear benefit, giving false hope to both patients and their families.
Konofagou's ultrasound approach could potentially boost the effects of drugs like aducanumab. "Our technique can be seamlessly combined with aducanumab in early Alzheimer's, where it has shown the most promise, to further enhance both its amyloid load reduction and further reduce cognitive deficits while using exactly the same drug regimen otherwise," she says. For the Columbia team, the goal is to use ultrasound to maximize the effects of aducanumab, as they've done with other drugs in animal studies.
But Konofagou's approach could transcend drug controversies, and even drugs altogether. The big promise of ultrasound is that it could eventually make drugs for Alzheimer's obsolete.
"There are already indications that the immune system is alerted each time ultrasound is exerted on the brain or when the brain barrier is being penetrated and gets activated, which on its own may have sufficient therapeutic effects," says Konofagou. Her team is now working with psychiatrists in hopes of using brain stimulation to treat patients with depression.
The potential to modulate the brain without drugs is huge and untapped, says Kim Butts Pauly, a professor of radiology, electrical engineering and bioengineering at Stanford University, who's not involved in the Columbia study. But she admits that scientists don't know how to fully control ultrasound in the brain yet. "We're only at the starting point of getting the tools to understand and harness how ultrasound microbubbles stimulate an immune response in the brain."
Meanwhile, the 74-year-old woman who received the ultrasound treatment last year, goes on about her life, having "both good days and bad days," her youngest daughter says. COVID-19's isolation took a toll on her, but both she and her daughters remain grateful for the opportunity to participate in the ultrasound trial.
"My mother wants to help, if not for herself, then for those who will follow her," the daughter says. She hopes her mother will be able to join the next phase of the trial, which will involve a drug in conjunction with the ultrasound treatment. "This may be the combination where the magic will happen," her daughter says.
If you were one of the millions who masked up, washed your hands thoroughly and socially distanced, pat yourself on the back—you may have helped change the course of human history.
Scientists say that thanks to these safety precautions, which were introduced in early 2020 as a way to stop transmission of the novel COVID-19 virus, a strain of influenza has been completely eliminated. This marks the first time in human history that a virus has been wiped out through non-pharmaceutical interventions, such as vaccines.
The flu shot, explained
Influenza viruses type A and B are responsible for the majority of human illnesses and the flu season.
Centers for Disease Control
For more than a decade, flu shots have protected against two types of the influenza virus–type A and type B. While there are four different strains of influenza in existence (A, B, C, and D), only strains A, B, and C are capable of infecting humans, and only A and B cause pandemics. In other words, if you catch the flu during flu season, you’re most likely sick with flu type A or B.
Flu vaccines contain inactivated—or dead—influenza virus. These inactivated viruses can’t cause sickness in humans, but when administered as part of a vaccine, they teach a person’s immune system to recognize and kill those viruses when they’re encountered in the wild.
Each spring, a panel of experts gives a recommendation to the US Food and Drug Administration on which strains of each flu type to include in that year’s flu vaccine, depending on what surveillance data says is circulating and what they believe is likely to cause the most illness during the upcoming flu season. For the past decade, Americans have had access to vaccines that provide protection against two strains of influenza A and two lineages of influenza B, known as the Victoria lineage and the Yamagata lineage. But this year, the seasonal flu shot won’t include the Yamagata strain, because the Yamagata strain is no longer circulating among humans.
How Yamagata Disappeared
Flu surveillance data from the Global Initiative on Sharing All Influenza Data (GISAID) shows that the Yamagata lineage of flu type B has not been sequenced since April 2020.
Nature
Experts believe that the Yamagata lineage had already been in decline before the pandemic hit, likely because the strain was naturally less capable of infecting large numbers of people compared to the other strains. When the COVID-19 pandemic hit, the resulting safety precautions such as social distancing, isolating, hand-washing, and masking were enough to drive the virus into extinction completely.
Because the strain hasn’t been circulating since 2020, the FDA elected to remove the Yamagata strain from the seasonal flu vaccine. This will mark the first time since 2012 that the annual flu shot will be trivalent (three-component) rather than quadrivalent (four-component).
Should I still get the flu shot?
The flu shot will protect against fewer strains this year—but that doesn’t mean we should skip it. Influenza places a substantial health burden on the United States every year, responsible for hundreds of thousands of hospitalizations and tens of thousands of deaths. The flu shot has been shown to prevent millions of illnesses each year (more than six million during the 2022-2023 season). And while it’s still possible to catch the flu after getting the flu shot, studies show that people are far less likely to be hospitalized or die when they’re vaccinated.
Another unexpected benefit of dropping the Yamagata strain from the seasonal vaccine? This will possibly make production of the flu vaccine faster, and enable manufacturers to make more vaccines, helping countries who have a flu vaccine shortage and potentially saving millions more lives.
After his grandmother’s dementia diagnosis, one man invented a snack to keep her healthy and hydrated.
On a visit to his grandmother’s nursing home in 2016, college student Lewis Hornby made a shocking discovery: Dehydration is a common (and dangerous) problem among seniors—especially those that are diagnosed with dementia.
Hornby’s grandmother, Pat, had always had difficulty keeping up her water intake as she got older, a common issue with seniors. As we age, our body composition changes, and we naturally hold less water than younger adults or children, so it’s easier to become dehydrated quickly if those fluids aren’t replenished. What’s more, our thirst signals diminish naturally as we age as well—meaning our body is not as good as it once was in letting us know that we need to rehydrate. This often creates a perfect storm that commonly leads to dehydration. In Pat’s case, her dehydration was so severe she nearly died.
When Lewis Hornby visited his grandmother at her nursing home afterward, he learned that dehydration especially affects people with dementia, as they often don’t feel thirst cues at all, or may not recognize how to use cups correctly. But while dementia patients often don’t remember to drink water, it seemed to Hornby that they had less problem remembering to eat, particularly candy.
Where people with dementia often forget to drink water, they're more likely to pick up a colorful snack, Hornby found. alzheimers.org.uk
Hornby wanted to create a solution for elderly people who struggled keeping their fluid intake up. He spent the next eighteen months researching and designing a solution and securing funding for his project. In 2019, Hornby won a sizable grant from the Alzheimer’s Society, a UK-based care and research charity for people with dementia and their caregivers. Together, through the charity’s Accelerator Program, they created a bite-sized, sugar-free, edible jelly drop that looked and tasted like candy. The candy, called Jelly Drops, contained 95% water and electrolytes—important minerals that are often lost during dehydration. The final product launched in 2020—and was an immediate success. The drops were able to provide extra hydration to the elderly, as well as help keep dementia patients safe, since dehydration commonly leads to confusion, hospitalization, and sometimes even death.
Not only did Jelly Drops quickly become a favorite snack among dementia patients in the UK, but they were able to provide an additional boost of hydration to hospital workers during the pandemic. In NHS coronavirus hospital wards, patients infected with the virus were regularly given Jelly Drops to keep their fluid levels normal—and staff members snacked on them as well, since long shifts and personal protective equipment (PPE) they were required to wear often left them feeling parched.
In April 2022, Jelly Drops launched in the United States. The company continues to donate 1% of its profits to help fund Alzheimer’s research.