Ohio State Mounts Multiple Attacks Against Dementia

Christopher Johnston
David and Kim Shorr work on a puzzle together at their home.

Kim and David Shorr of Bexley recently found themselves on the frontlines of the ongoing battle to treat and eventually cure Alzheimer’s disease.

Roughly eight years ago, David began to notice something was wrong. “I realized I had a problem through other people’s reactions when I couldn’t remember things,” he says. “I was searching for things in my brain, and I didn’t know why I couldn’t function mentally.”

When he was officially diagnosed three years ago, David, 59, joined the estimated 5.8 million Americans currently living with the devastating neurodegenerative disease, according to the national Alzheimer’s Association’s 2019 Alzheimer’s Disease Facts and Figures Report.

He had received care for more than a year at OSU’s Wexner Medical Center, when the couple learned of a clinical trial that might help David. After completing a long battery of blood work and diagnostic scans that took several months, he qualified. In May, he began participating in the clinical trial that employs a noninvasive technology known as focused ultrasound, a low-intensity, concentrated band of ultrasound beams used to penetrate the blood-brain barrier.

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Although the protective membrane shields the brain from infections and pathogens and is beneficial for normal brain function, it becomes a serious challenge when trying to permeate the brain with potentially therapeutic medicines for diseases such as Alzheimer’s, says Dr. 

Vibhor Krishna, a neurosurgeon at Ohio State’s Wexner Medical Center.

“Some molecules like glucose or oxygen can pass through the blood-brain barrier, but larger molecules, especially drugs, won’t pass through,” he says. “So this has been a major roadblock in delivering potential therapeutics for Alzheimer’s disease.”

Researchers believe the ultrasound technology will break down the build-up of amyloid plaque, an abnormal clumping of proteins in the brain believed to be the underlying reason for Alzheimer’s and other neurological disorders. Thus, the goal of the procedure is to remove as much amyloid plaque as possible and determine whether the ultrasound technique effectively opens the blood-brain barrier so that medications could be delivered to help develop new treatments for brain tumors or epilepsy, for example.

“We launched this phase-one trial to first look at the safety again of opening the blood-brain barrier in patients with Alzheimer’s disease,” says Krishna, adding that a pilot study in Canada demonstrated that patients tolerated the procedure well and did not have side effects. “Secondly, we wanted to see its effect on clearance of plaque on the brain.”

The procedure required David to have his head shaved so that the helmet-like halo device could be attached securely to his head via screws. The focused ultrasound waves then cause microbubbles in the blood to oscillate and open the blood-brain barrier.

After three treatments at two-week intervals, the doctors told the Shorrs they have seen a 5 percent decrease in the plaque, although David had not experienced any improvements in his condition. However, the Shorrs fully understood the nature of early clinical trials and appreciate all of the thoughtful care they have received.

“We went into it knowing that it probably won’t help David, but may help others in the future,” Kim says. “We are hopeful that it will help him, but we’re realistic.”

At press time, David was scheduled for a follow-up visit to take neurological and neuro-psychological exams to assess his language, memory and executive functioning skills. The entire study will take about a year and a half to complete, Krishna says.

The innovative study represents one of more than 20 active clinical trials related to dementia that researchers at OSU’s Wexner Medical Center are currently conducting. Alzheimer’s and dementia disorders are now projected to affect nearly 14 million people by 2050.

Another local advancement has been development of the SAGE test, which provides early Alzheimer’s and dementia detection. SAGE stands for Self-Administered Gerocognitive Examination.

Dr. Douglas Scharre, a professor of clinical neurology and psychiatry who directs OSU’s Center for Cognitive and Memory Disorders, and his team of researchers first developed the SAGE test in 2008 and then unveiled an advanced version in 2014, after publishing an updated study.

Scharre explains that he was concerned by data showing that, on average, people don’t mention memory or cognitive concerns to their primary care physician for three-and-a-half years after symptoms start. By the time the patient sees a neurologist, it may be another year. Unlike cardiac bypass or diabetes, for example, people consider memory loss more embarrassing or just a natural part of aging and are less likely to mention it.

“The main issue that caused me to invent this test was that people were coming in much later than they should be,” Scharre says. “So with the test, if you’re not doing well, we’re picking you up for care at year one rather than year four, then we have a lot more options that we can treat early.”

To date, the free, at-home cognitive test is one of the only self-administered tests of its kind and has had more than 2.3 million downloads worldwide—a fact that greatly pleases Scharre. The test has already been translated into Italian and Spanish, the French version is now being created, and a German version may soon follow.

“It continues to be the most visited website at OSU,” he says. “So it’s been very popular and that’s been very gratifying.”

The largest center for Alzheimer’s clinical research in Ohio, OSU’s Wexner Medical Center is studying a full gamut of diseases and disorders, from mild cognitive impairment to frontal temporal dementia.

Currently, it is one of 23 Centers for Excellence in the U.S. studying ways to improve diagnosis of another type of brain disease, Lewy body dementia, which is characterized by abnormal deposits of a protein called alpha-synuclein. Among those who may experience Lewy body dementia are people diagnosed with Parkinson’s disease.

Lewy body dementia is second only to Alzheimer’s when it comes to progressive dementias, and its symptoms include movement difficulties—such as tremors, slowness and stiffness—as well as significant thinking and memory problems

“The outlook looks much better than it did five years ago for finding improved disease-modifying treatments for a lot of these conditions,” Scharre says. “So, if you can get evaluated and diagnosed sooner, we can try to stave it off with the medications we have, keep your brain as healthy as we can, and then hopefully a treatment will come along so we can keep you going even further with a better quality of life.

Reprinted from Columbus Monthly Health 2020.