The National Institutes of Health/National Institute on Aging (NIH/NIA) has awarded Duke Anesthesiology’s Niccolò Terrando, BSc, DIC, PhD, a five-year, $2,815,756 R01 Award for his project, titled “Neurovascular dysfunction in delirium superimposed on dementia.”
Millions of Americans live with dementia and require common surgical interventions, such as orthopaedic surgery. According to the research statement, these potentially life-saving procedures often increase the risk for further cognitive deterioration and in many cases, even death. Dr. Terrando with his team of investigators at Duke University (Carol Colton, Gurpreet Baht, William Wetsel, Zhiquan Zhang, and Miles Berger) and University of Rochester Medical Center (Harris Gelbard) will address this public health concern by providing fundamental knowledge expected to help reduce the burdens of neurologic complications after common surgical procedures, and improve the quality of life for these high-risk patients.
The rationale for the proposed research is that successful completion of these studies will advance and expand the understanding of how surgery affects the blood-brain interface, and will provide new insights into molecular mechanisms of relevance to delirium, neurodegeneration and aging. Such knowledge is highly significant because it has the potential to improve surgical outcomes and quality of life for millions of vulnerable, elderly patients in the United States by using new therapeutic approaches tested in this grant.
As stated in the project’s abstract, impaired cognitive function after common surgical procedures is a growing concern, especially among the more than five million people in the nation who suffer from dementia, including Alzheimer’s disease (AD), and thus have a three-fold increased risk for fracture requiring surgical repair. After orthopaedic surgery, acute changes in cognitive function, often referred to as postoperative delirium, occur in up to 89 percent of patients with preexisting dementia, and associate with poorer prognosis and even two-fold greater risk for one-year mortality compared to patients without dementia or delirium. This proposal will attempt to model postoperative delirium superimposed on dementia after orthopaedic surgery using innovative approaches to understand, and possibly attenuate, the effects of surgery on the blood–brain interface, including the neurovascular unit (NVU) and the blood-brain barrier (BBB).
The long-term goal of Dr. Terrando and his team of investigators is to define the mechanisms that underlie surgery-induced cognitive dysfunction, and to provide safe and effective approaches to reduce this potentially devastating complication.
Dr. Terrando joined Duke in 2015 and is an assistant professor in anesthesiology, the director of the Neuroinflammation and Cognitive Outcomes Laboratory, a collaborator of Duke Anesthesiology’s Center for Translational Pain Medicine and a 2016 DREAM Innovation Grant (DIG) recipient for his research project, titled “The Systemic Milieu and its Role in Postoperative Cognitive Dysfunction.”