The Daily Dose • Friday, May 24, 2024

From Bench to Brain Health: Developing Translational Expertise to Better Integrate Modern Neuroscience in Patient Care

Connor Brenna, MD

Cognitive function is a key element of postoperative recovery. Consequently, for anesthesiologists serving an aging surgical population, patient cognition is increasingly front of mind. In a session on Friday, May 17, cosponsored by Early-Stage Anesthesiology Scholars (eSAS) at the 2024 Annual Meeting, presented by IARS and SOCCA, “Leveraging Translational Neuroscience to Understand Postoperative Neurocognitive Disorders in Humans: Insights from Young Investigators,” three early-career experts shared their experience using translational science to safeguard perioperative brain health.

Michael Devinney, MD, PhD, an assistant professor and critical care physician-scientist in the department of anesthesiology at Duke University both moderated the session and presented on “Blood‐Brain Barrier Dysfunction in Postoperative Delirium: Translating Findings from Animal Models.” Postoperative delirium (POD) has many known risk factors, but what triggers this condition is still poorly understood. However, research in animal models has implicated the blood-brain barrier (BBB), which regulates the passage of substances — including toxins — between the circulation and the brain. For example, mouse models of orthopedic trauma (e.g., tibial fracture) develop a POD-like phenotype corresponding with a transient “opening” of the BBB, measured as the leaking of circulating molecules into the brain. Dr. Devinney presented data from the paper “Role of Blood–Brain Barrier Dysfunction in Delirium following Non-cardiac Surgery in Older Adults,” which evaluated the cerebrospinal fluid-to-plasma albumin ratio (CPAR) as a surrogate for BBB integrity in a cohort of 207 older adults undergoing noncardiac surgery. Interestingly, while a modest increase in CPAR was associated with the development of POD, Dr. Devinney’s work showed that this was not driven by a postsurgical increase in cerebrospinal fluid albumin — rather, a decrease in serum albumin strongly predicted POD. Whether this is causal or correlative, and what role the BBB might play in POD among surgical patients, remain exciting translational frontiers for our field.

In “Prehabilitation for the Brain: Exploring the Role of Functional Connectivity, Brain Resilience, and Computerized Cognitive Training,” Kimberly Rengel, MD, MSCI, assistant professor of anesthesiology in the department of anesthesiology, division of critical care medicine at Vanderbilt University, presented perioperative cognition through the lens of network models. Prior work by van Montfort and colleagues has evaluated functional networks in POD, in “Brain network disintegration as a final common pathway for delirium: a systematic review and qualitative meta-analysis,” and concluded that brain network disintegration is a hallmark of the phenomenon. However, preclinical work demonstrates that functional networks can be fortified, for example, through “cognitive training” or physical exercise. Dr. Rengel presented findings from “A randomised pilot trial of combined cognitive and physical exercise prehabilitation to improve outcomes in surgical patients.” This pilot trial randomized patients undergoing major noncardiac surgery to receive a combination of cognitive training (adaptive digital games) and physical exercise versus active attention (a control group receiving generalized health information only). Although powered for feasibility, its results did trend towards improved postoperative cognitive function in the former group. A full 250-patient trial powered for cognitive outcomes is highly anticipated: COgnitive and Physical Exercise to Improve Outcomes After Surgery (COPE-iOS) is expected to conclude in 2026.

Finally, in “Postoperative Neurocognitive Disorders following Traumatic Brain Injury,” Christopher Roberts, MD, PhD, assistant professor and staff physician in the department of anesthesiology at the Medical College of Wisconsin, detailed the potential interplay between traumatic brain injury (TBI) and postoperative cognitive outcomes. Preclinical data illustrate that anesthetic drugs, as well as TBI, independently have lasting effects on the brain. Dr. Roberts’ work investigates the hypothesis that these effects may be additive or even synergistic by examining cognitive function among patients who experience TBI and subsequently undergo either extracranial surgery or no surgery. This work was first reported in “Clinical Outcomes After Traumatic Brain Injury and Exposure to Extracranial Surgery,” which described an association between extracranial surgery (and anesthesia) and adverse functional outcomes at 2 weeks and 6 months after TBI. That intriguing pattern persisted at a 1-year follow-up: extracranial surgery was associated with distinct cognitive trajectories for many patients with complicated mild TBI and moderate-to-severe TBI. These findings identify TBI as an important and yet understudied risk factor for the development of postoperative cognitive impairment. Whether a recent, incidental TBI should justify delaying elective surgery is a priority area for future research.

Cognition is an important postoperative outcome, but — as a composite endpoint with many potential confounders — is challenging to study. Fortunately, preclinical research is uncovering some of its important components, and these early-career experts illustrate the successful implementation of translational neuroscience to examine them in the context of perioperative cognitive function. Collectively, this work underscores the value of developing our community’s translational expertise to better integrate modern neuroscience into the care we give our patients.