PLASTICITY IN RECOVERY FROM SURGERY: THE EFFECTS OF EXERCISE "PREHABILITATION" ON COGNITIVE AND FUNCTIONAL RECOVERY AFTER SURGERY IN OLDER ADULTS

Principal Investigator:  Richard P. Sloan, Ph.D.

Post-Operative Delirium (POD) imposes significant costs on patients, their families and caretakers, and more broadly on society as a whole. Older patients undergoing surgery are at significantly elevated risk of cognitive impairment, memory decline, and need for long-term care. Developing an intervention to reduce POD and unravel the pathophysiology of POD and delayed recovery is of high clinical impact. Systemic inflammation plays an important role in cognitive dysfunction as it exerts ripple effects on individual organs including the brain. Systemic inflammatory events influence neuroinflammation via well-established pathways including passive diffusion and active transport of inflammatory mediators across the blood brain barrier (BBB), secretion of such mediators by endothelial cells, and through peripheral neuronal input. Clinical studies in the aging population consistently show a robust association between systemic inflammation, memory impairment, and cognitive decline.  Similarly, peripheral inflammatory markers are elevated in patients suffering from Alzheimer’s disease and are strongly associated with the development of cognitive decline in patients suffering from metabolic syndrome (obesity, dyslipidemia, hypertension, elevated glucose), a highly prevalent clinical condition.

We and others have shown that aerobic exercise training programs reduce systemic inflammation.  If post-operative delirium is the product of increased inflammation secondary to surgical trauma, then it may be possible to intervene before surgery to prevent this surgically-induced delirium.  Animal studies suggest that pre-treatment with exercise interventions before experimental surgery reduces post-operative cognitive dysfunction.  However, there are no corresponding human studies.  In this pilot study, we propose an initial investigation of this effect.  We will recruit 20 patients awaiting shoulder replacement surgery, an elective procedure that can be scheduled early enough so that we can deliver a 4-week high intensity interval aerobic training program to be completed before surgery.  Patients will be randomized to receive the exercise training program or to receive usual care.  They will be measured for post-operative delirium immediately following surgery and daily thereafter for 3 days.  In addition, we will draw blood to measure levels of inflammatory markers in the training and control groups.  Our aim is to collect sufficiently impressive pilot data to submit a competitive application for a full-scale study to the National Institutes of Health

Marna Freed