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Can Ultrasound Help Treat Alzheimer’s?

New research suggests the technology could one day be a helpful tool in tackling the disease

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Imagine strapping on a high-tech helmet, lying on an MRI table and, after microbubbles bounce in your blood vessels and ultrasound waves are beamed at your brain, walking away with fewer symptoms of Alzheimer’s disease.

That may sound like it’s straight out of a science fiction movie, but it’s not. What’s called focused ultrasound technology is just one of the many avenues scientists are exploring in an ongoing quest to effectively treat the most common type of dementia. And a new study published in the New England Journal of Medicine suggests it may be able to help.

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Researchers at the Rockefeller Neuroscience Institute at West Virginia University found that when used alongside a new Alzheimer’s drug, focused ultrasound helped the medication do its job — clearing sticky, cell-disrupting amyloid plaques — more effectively in a small number of patients.

“We need to really explore and be bold in terms of the way we’re looking at Alzheimer’s, because the disease is not going away, it’s increasing,” says neurosurgeon Ali Rezai, M.D., executive chair of the Rockefeller Neuroscience Institute and a coauthor of the study.

The number of people living with dementia, including Alzheimer’s disease, globally is expected to nearly triple by 2050, a 2021 report published in The Lancet predicts. And while two disease-modifying treatments have recently become available, it’s still unclear how beneficial they are to people living with Alzheimer’s.

“In the field, we’re certainly keeping all options open,” says Ronald Petersen, M.D., an Alzheimer’s expert and director of the Mayo Clinic Alzheimer’s Disease Research Center, who is not involved in focused ultrasound research. “Because treatments are not going to result in a silver bullet for Alzheimer’s disease.”

How can ultrasound help?

It all comes down to what’s known as the blood-brain barrier — a roadblock of sorts that keeps harmful substances (viruses, bacteria and the like) from entering the brain. It also impedes the direct delivery of potentially helpful drugs.

Rezai’s research, however, shows that low-intensity ultrasound waves targeted at specific regions of the brain can temporarily and safely open the blood-brain barrier, lending a novel way to deliver drugs and therapeutics straight to the source.

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“Most of the things that are really cutting-edge and interesting, like gene therapies and cell therapies, require you to directly inject them into the brain,” says Michael Kaplitt, M.D., a neurosurgeon and vice chair for research at Weill Cornell Medicine, who has worked with Rezai on focused ultrasound research. “What if you could do this without brain surgery?”

In the New England Journal of Medicine study, published Jan. 4, 2024, Rezai and his team tested the concept on three patients with mild Alzheimer’s disease.

These patients received six standard monthly infusions of aducanumab — an anti-amyloid medication that received accelerated approval from the Food and Drug Administration (FDA) in 2021 — immediately followed by ultrasound therapy to open the blood-brain barrier in regions with a high concentration of amyloid plaques.

After six months of antibody and ultrasound treatment, the researchers observed an average of 32 percent greater reduction in amyloid plaques in brain areas where the blood-brain barrier was breached than in areas where it was not opened.

The study was not designed to measure clinical outcomes, so it’s unclear at this point whether the greater removal of amyloid conveys any meaningful benefit, like symptom relief, to patients.

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Researchers plan to begin the next phase of the trial this year, looking at focused ultrasound in combination with lecanemab, a newer and more effective anti-amyloid medication that received FDA approval in the summer of 2023.

In an accompanying editorial, researcher Kullervo Hynynen writes that “additional studies are needed to establish long-term safety and efficacy, and cost-effective treatment devices that are not reliant on online MRI guidance must be developed for broader accessibility.” Still, he says, “the results spark optimism that this approach to treatment, together with agents that remove [amyloid], could eventually slow the progression of Alzheimer’s disease.”

Lifestyle changes may reduce Alzheimer’s risk ​​

Research isn’t just focused on treatments. We’re learning more about how everyday habits may help reduce dementia risks. Here are 10 behaviors that could be a boon for the brain: ​​

  • Regular physical exercise 
  • A heart-healthy diet
  • Strong social connections 
  • Controlling high blood pressure​
  • Not smoking
  • Getting plenty of sleep
  • Staying mentally active
  • Treating hearing problems ​
  • Taking care of your mental health​
  • Managing your blood sugar ​​

Source: U.S. Department of Health and Human Services

How it works: Punching “little holes” in the barrier

First, it’s helpful to know that focused ultrasound isn’t new to medicine. It’s already used to treat symptoms of other neurodegenerative conditions, like essential tremor and Parkinson’s disease. The experimental technique that’s being explored in clinical trials for Alzheimer’s, however, is different. (It’s also different from the more routine ultrasound procedures that let expecting parents peek at their developing babies or that allow doctors to see the pumping action of the heart.)

The high-tech helmet at the center of the Alzheimer’s research is attached to an MRI and contains more than 1,000 probes that emit low-intensity ultrasound waves at specific targeted areas of the brain. The patient’s head goes into the helmet, then microscopic bubbles get injected into their bloodstream. These bubbles, which are used in other imaging procedures, look like a relatively clear fluid, Kaplitt says, and can’t be felt by the patient.

When the tiny bubbles meet the energy from the ultrasound, they start to bounce around in that specific spot “and literally punch holes in this blood-brain barrier,” Kaplitt explains, causing it to open at the target without disturbing other areas of the brain. Within 24 hours, the barrier is closed again. So far, no adverse events have been reported among the patients who have undergone this procedure since the research began a few years ago.

“I think the most important thing that we’ve been showing is that this seems to be very safe and well tolerated,” Kaplitt says.

Fitting into the future of medicine

Rezai and Kaplitt aren’t the only researchers pursuing focused ultrasound for Alzheimer’s treatment. A handful of other U.S.-based institutions are studying the approach, as are Canadian researchers. At the same time, scientists are looking at a myriad of technologies, targets and therapies that could potentially hold the answer — or at least part of one — to treating Alzheimer’s.

“It’s likely going to be a combination of treatments that will ultimately be effective at staving off some of the cognitive impairment of aging,” the Mayo Clinic’s Petersen says.

It’s not clear whether ultrasound will fit into that mix, but Rezai is optimistic that it will play a role in how we treat brain diseases in the future. “It opens up a whole new set of opportunities for us as physicians and scientists to explore — not only for Alzheimer’s but for other neurological conditions,” he says. 

Editor’s note: The story, first published March 7, 2022, has been updated to include new research.

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