En español | Almost 6 million Americans live with Alzheimer's, a devastating disease for which there is no known cure. Judi Polak, 62, is one of them. She's also one of the much smaller number of people who've signed on to let researchers experiment on their ailing brains — in her case, having ultrasound energy beamed into her hippocampus, the brain's memory center.
Perhaps surprisingly, Judi didn't think twice about joining the groundbreaking clinical trial, which she describes as part of her active fight against the disease she was diagnosed with four years ago. “We all have a lot of inner strength,” Judi says of her family (which includes her husband, Mark Polak, three grown daughters and two dogs). “One of our good friends said that the first person to [one day] be cured with Alzheimer's is alive today. That became our mantra and fight song. I choose not to suffer, not to die, but to fight."
It's a fitting motto for a woman whose husband describes her as a “butterfly on acid.” “Before Judi's diagnosis, I'd joke that Judi didn't just burn the candle on both ends — she set fire to the middle,” Mark says.
As a neonatal nurse practitioner at the West Virginia University (WVU) hospital who also taught at the nursing school, Judi first began experiencing Alzheimer's symptoms related to coming up with a word or figuring out basic math. “I just thought I had depression because I was having trouble putting things together,” she recalls. “The Alzheimer's diagnosis slammed me in my face. I kept thinking, ‘This can't be happening to me. I'm 58, with no family history.’ There was a lot of denial."
It didn't help that the Polaks felt that the specialists they consulted were extremely negative about her prognosis. “I felt like all the experts were advising Judi to sit at home and not do anything,” recalls her husband. “But that's not Judi. She's always had an extremely full life.” When they learned about a potential clinical trial taking place at WVU, the couple jumped at the chance to join it. “When I was wheeled into the MRI room last October and saw a sea of people watching me, it really overwhelmed me,” Judi recalls. “It wasn't just for myself — it was a chance to make history."
The treatment being tested, known as focused ultrasound, opens up the blood-brain barrier, the semipermeable membrane that surrounds blood vessels in the brain. This barrier is necessary to keep out germs, but it also prevents potential Alzheimer's drugs from reaching the brain. “This is one reason why we think past medication treatments for Alzheimer's have not been effective,” says neurosurgeon Ali Rezai, director of the Rockefeller Neuroscience Institute at the WVU School of Medicine.
To participate, Judi underwent an MRI with a million-dollar helmet on her head containing more than 1,000 tiny probes emitting ultrasound straight to her hippocampus. In the meantime, microbubbles injected into her bloodstream traveled through her circulatory system. “As the microbubbles went by the area hit by ultrasound, they thought it was a disco, and they started dancing and bounced against the walls and cracked open the blood-brain barrier,” Mark says. That is, the vibration of the microparticles let them fit through the opening forged by the ultrasound.
When the medical team injected a contrast agent in Judi's brain, proof of such penetration was visible in the MRI imaging. But just as neatly as the blood-brain membrane opened, a repeat MRI 24 hours later showed that it had closed. “That's important, because you don't want it open for long, since it could theoretically allow toxins or germs in,” Rezai says.
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Both Polak and her husband think the focused ultrasound treatment had an immediate effect. “For years, Judi's eyes had had this dead look, almost a zombie stare, which I attributed to her Alzheimer's,” says Mark, a neonatologist at WVU Medicine. “But when she was wheeled out of the MRI machine after the procedure, her eyes were lit back up.”
Judi underwent two more scans over the following six weeks. In the subsequent months, both Mark and Judi noticed a change. “She's now able to follow directions more easily, and seems less confused, especially during the daytime,” says her husband.
The explanation for how this could be possible, Rezai says, can be found in similar tests on mice. In those, ultrasound was shown to clear away two abnormal proteins believed to play a key role in causing Alzheimer's — beta amyloid and tau, which create clumps and tangles inside and between brain neurons — and to also improve cognition.
"While it's still too early to say for sure, we think the focused ultrasound alone is having the same effect on Judi and the other five patients who have participated in this clinical trial,” Rezai says. “We have noticed that the treated areas have a decrease in these plaques, compared to other parts of the brain that we didn't treat.”
One theory is that the ultrasound triggers an immune response, which leads the brain to clear out the plaques and tangles as waste. “I explain it to people as, ‘We opened Judi's attic door and her immune system looked up and saw all these cobwebs and decided to grab some Swiffers and clean them all out,'” Mark says.
The experts say it's too early to tell whether Judi's symptoms have improved, but the Polaks stay positive. Judi continues to volunteer at the Neonatal Intensive Care Unit at WVU Medicine Children's Hospital, where she cuddles babies and catches up with old colleagues. She goes to the gym three times a week, helps take care of her aging mother (who moved in with the couple several weeks ago) and reads as much as she can. “I used to be a voracious reader, but when I was first diagnosed with Alzheimer's I found I couldn't read at all,” she says. “Now, after the treatment, I'm able to follow what I'm reading, although it can still be very choppy.”
Although promising, focused ultrasound for Alzheimer's is still in its very early stages, notes Rezai. The next step will be to do larger studies, in more patients, evaluating the safety of opening the blood-brain barrier as well as seeing if the treatment consistently results in the reduction of debilitating plaques. “Even then, we'll still need to see if getting rid of plaques helps reduce cognitive decline and improve memory and brain function,” he says, adding that this could take years.
Assuming such effects are established, Rezai hopes to be able to use this technology as a more effective way of introducing stem cell treatments or gene therapy to the brain. “It's not just Alzheimer's disease — this technology could open up a whole new window of opportunity to treat other degenerative neurological conditions, like Parkinson's,” he says.
Meanwhile, the Polaks try to live life day by day. “Any improvement is a victory,” says Mark. “If it means we get to keep Judi alert for a few more months, weeks, even days or hours, it's worth it."