A new review paper published this month in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association underscores the need for high-quality animal models to advance the understanding of the neurobiology of delirium. The paper, facilitated by the NIH-funded Network for Investigation of Delirium: Unifying Scientists (NIDUS), presents recommendations to scientists – particularly those new to delirium research – on best-practices, limitations, and challenges involved in developing and validating robust models that accurately replicate elements of human delirium in animals.
One of the two first authors of the paper, Preclinical and Translational Models for Delirium: Recommendations for Future Research from the NIDUS Delirium Network, is Nadia Lunardi, MD, PhD, Associate Professor of Anesthesiology and faculty member of the Neuroscience Graduate Program at the University of Virginia.
“As a Critical Care physician, delirium is a daily challenge. At least one third of the postoperative patients age 65 and older I care for in the Intensive Care Unit suffers from this form of acute brain failure, characterized by confusion, inattention, lethargy or agitation, and perceptual disturbances” explains Dr. Lunardi. “In elderly patients undergoing major surgery and requiring prolonged mechanical ventilation in the Intensive Care Unit, the incidence of delirium can be as high as 80-85%. A diagnosis of delirium carries a poor prognosis as it increases the likelihood of prolonged hospitalization, functional decline, and even death, and results in healthcare costs of $150 billion annually” she notes.
“Although in the past decade knowledge about the epidemiology, risk factors, and outcomes of delirium has grown tremendously thanks to clinical studies, our understanding of the causative mechanisms of delirium has been lagging. This is largely due to the lack of robust animal models that can be used to test specific hypotheses through careful experimental manipulations” she warns.
To address the lack of mechanistic understanding of delirium pathophysiology, Dr. Lunardi and her team have focused on developing and validating a novel mouse model of postoperative delirium that recapitulates the realism of the clinical setting by subjecting aged mice to anesthesia, surgery and a simulated ICU environment.
“It is my hope and that of my co-authors that this paper will offer conceptual and practical insights for new researchers interested in delirium, by outlining both the promises and pitfalls of preclinical and translational models in advancing our current knowledge of delirium pathophysiology, and informing the development of new preventative and treatment strategies” concluded Dr. Lunardi.
The work was co-authored by Sarinnapha M. Vasunilashorn, PhD, of Harvard Medical School (co-first author); Sharon K. Inouye, MD, MPH, of Harvard Medical School (co-senior author); Roderic Eckenhoff, MD, of the University of Pennsylvania (co-senior author), and Niccolo’ Terrando, PhD, of Duke University (co-senior author), along with 13 interdisciplinary experts from institutions around the world.