Emerging Science
Meet five trailblazers from Cleveland Clinic’s Neurological Institute who are transforming care and pushing boundaries with their research.
FEATURE
By John Soeder
Photos: Shawn Green and Marty Carrick
Dr. Andrew Bender
The Technologist
Could the built-in resilience of the brain itself be a formidable weapon in the fight against dementia and neurodegenerative diseases? Andrew Bender, PhD, is on a mission to find out. He’s a neuroscientist at Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas.
Central to Dr. Bender’s research is the innovative use of diffusion MRI, a technique that measures the movement of water molecules in the brain. This allows for an unprecedented look at the brain’s microstructure, revealing changes that are invisible to other methods. Such detailed insights are crucial for identifying the early stages of Alzheimer’s disease and other forms of dementia.
A centerpiece of Dr. Bender’s work is his study of “cognitive resilience” — the concept that some individuals, despite having neuropathological features of Alzheimer’s, do not exhibit cognitive impairment. His goal is to find neuroimaging biomarkers that can predict resilience, facilitating early intervention and personalized treatment.
“The idea is to develop biomarkers of resilience that can be utilized for a host of different disorders — something that can be deployed in a clinic or during clinical trials, where we know a treatment is working because we’re seeing changes in these measures,” says Dr. Bender, who received an Emerging Scientist Career Award from the Neurological Institute.
These biomarkers could provide more precise means for diagnosing, monitoring and treating not only Alzheimer’s, but Parkinson’s disease, multiple sclerosis and other neurodegenerative diseases.
Dr. Bender foresees a brighter future where advanced computational methods, including AI, integrate seamlessly with neuroimaging techniques to provide holistic insights into brain health. “To account for not just what’s happening in the brain but the whole constellation of individual-based measures, we need a far more accurate prognostic tool,” he says. “While this is an ambitious goal, if you don’t aim high, you’ll never get there.”
Dr. Tatiana Falcone
The Interventionist
One insight at a time, Tatiana Falcone, MD, MPH, is transforming the way we address mental health in children and adolescents.
The main thrust of her work is suicide prevention. “I focus on identifying biological or clinical risk factors that can improve our chances of recognizing when someone is at risk for suicide, as well as interventions that can help diminish suicidal thoughts,” says Dr. Falcone, a psychiatrist in Cleveland Clinic’s Neurological Institute and Cleveland Clinic Children’s.
Through her study of biological triggers associated with mood disorders and suicidal thoughts, Dr. Falcone found that low levels of serotonin are associated with an increased risk of suicide among adolescents. Such biomarkers could lead toward objective tests for mental health conditions and improve our ability to recognize objectively when someone is at immediate risk for suicide.
Determined to bridge the gap between recognizing mental health issues and delivering timely, effective interventions, Dr. Falcone is coming at suicide prevention from multiple angles. She oversees a randomized control trial that pairs ketamine infusions with Collaborative Assessment and Management of Suicidality (CAMS) therapy to reduce suicidality. In Cleveland Clinic’s Epilepsy Center, she has implemented a pioneering screening process to identify pediatric patients with depression and anxiety symptoms. Her Project HOPE aims to reduce anxiety and depression via a web-based application (created by Silvercloud/Amwell) and to improve the quality of life for youth with depression and anxiety in those with and without chronic illness.
Dr. Falcone also has written a book titled A Parent’s Guide to Prevent Suicide in Your Loved One, available in English and Spanish.
Her clinical practice is informed by her research — and vice versa. “It’s such a privilege to be a clinician and a scientist,” she says, “because you experience the problems your patients are having firsthand, which raises important questions and creates opportunities for better care.”
Dr. Nina Moore
The Precisionist
Did you know that blood courses differently through the brain than other parts of the body?
“The brain is the only place that has continuous auto-regulation to maintain constant blood flow,” says Nina Moore, MD, MSE, a neurosurgeon in Cleveland Clinic’s Neurological Institute. “The blood vessels in the brain are significantly different. There are no valves and no vein resistance.”
By applying engineering principles to the study of these vessels, Dr. Moore is advancing our understanding of the biomechanics of cerebrovascular disease. Her efforts center on cerebral aneurysms and cerebral arteriovenous malformations (AVMs), which are abnormal clusters of blood vessels where high-flow arteries connect directly to veins.
Using 7-Tesla MRI and other advanced imaging technologies as well as custom mechanical testing equipment, Dr. Moore’s lab performs computational fluid structure-interaction modeling of aneurysms and AVMs. These models make it possible to simulate fluid flow and understand the mechanical response of blood vessels.
The multifaceted research involves collaborations with colleagues across other specialties, including bioengineering, neuroimaging and neuropathology. “The collaborative environment at Cleveland Clinic elevates our work,” Dr. Moore says. “We have experts across fields, all in the same location.”
She hopes to write the book on cerebrovascular mechanics — literally. It would provide an invaluable reference not only for caregivers, but for developers of biomechanical devices. Dr. Moore is also excited about the implications for precision medicine. By integrating preoperative imaging data with biomechanical simulations, physicians would be able to provide individualized risk assessments and treatment plans for patients with cerebrovascular disease. In contrast to a one-size-fits-all approach, interventions could be tailored based on an individual’s specific anatomy and other unique attributes.
“With data from our simulations,” Dr. Moore says, “we would like to have a powerful clinical software tool to guide treatment in a more scientific way.”
Dr. Daniel Ontaneda
The Optimist
Daniel Ontaneda, MD, PhD, can see the progress we’ve made in the fight against multiple sclerosis. “When I started out in this field, many people in our lobby had significant disability,” says Dr. Ontaneda, a neurologist in Cleveland Clinic’s Mellen Center for Multiple Sclerosis. “When you look around today, you can’t tell if some people have MS. It’s a testament to the highly effective medications that we have now.”
Nonetheless, more work remains to be done. By identifying specific biomarkers, Dr. Ontaneda hopes to create an MRI-based diagnosis method that could simplify and reduce the need for prolonged clinical symptom monitoring and neurological exams. He is also utilizing MRI as a clinical trial endpoint to evaluate the effectiveness of new medications and treatment sequences. His current trial focuses on whether administering highly effective medications early in the disease can lead to better long-term outcomes.
Dr. Ontaneda has always been fascinated by the inner workings of the brain. “Nothing is more complex,” he says. “We’re talking about the pinnacle of human evolution.”
His contributions to MS research include the identification and validation of the central vein sign, an MRI-based biomarker that differentiates MS lesions from other conditions. Now integrated into the diagnostic criteria for the disease, CVS promises to promote earlier and more accurate diagnosis.
Dr. Ontaneda has focused on research to make the diagnosis of MS more accurate so we can then start highly effective treatments with confidence and ensure the best outcomes for people with MS.
“As an MS researcher, my goal is to help cure the disease,” he says. “Hopefully, we’ll see that within our lifetimes. To rid the world of MS and prevent people from developing it altogether is something we believe is attainable.”
Dr. Cinthya Peña-Orbea
The Activist
Obstructive sleep apnea (OSA) occurs when a blockage keeps air from moving through your airpipe while you’re asleep, which can lead to dangerous complications. It affects an estimated 5% to 10% of people worldwide, although the condition is more prevalent and underdiagnosed among people of color.
Cinthya Peña-Orbea, MD, a sleep medicine physician in Cleveland Clinic’s Neurological Institute, is dedicated to promoting health equity in sleep health. To this end, she is analyzing the impact of social determinants of health on OSA. Her research aims to uncover health-related social needs pathways driving the underdiagnosis of the condition, particularly among Hispanics/Latinos and other racial and ethnic minorities.
The results of a recent study by Dr. Peña-Orbea underscore a critical need. “We found that greater neighborhood socioeconomic disadvantage was associated with increased cardiovascular events in patients with obstructive sleep apnea,” she says.
Dr. Peña-Orbea is working to dismantle barriers to diagnosis and treatment. “Now I want to understand: What are the health-related social needs at the neighborhood and individual level that may influence the underdiagnosis of OSA?” she says. “Obtaining an OSA diagnosis and treatment can be complex, with barriers to care present at various levels. The extent to which these barriers affect referrals from primary care providers and patients’ completion of those referrals is unknown. We need to identify these barriers to develop culturally tailored interventions to decrease the underdiagnosis of OSA.”
Dr. Peña-Orbea received an Emerging Scientist Career Award from the Neurological Institute.
Up next? She plans to open a Hispanic Sleep Clinic within Cleveland Clinic that will offer special bilingual and bicultural sleep care to meet the needs of the Hispanic community.
“I’m passionate about this,” Dr. Peña-Orbea says. “Ultimately, I want to ensure that all patients have equitable access to quality care.”