Postoperative Delirium- Unmasking of Pre-existing Deficits, or De Novo Injury to the Brain
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PROJECT SUMMARY / ABSTRACT This is a K24 Midcareer Investigator Award in Patient-Oriented Research for Dr. Miles Berger, focused on mentoring research trainees in studies on the mechanisms of postoperative delirium, a syndrome of fluctuating changes in levels of consciousness and attention. Postoperative delirium is the most common post-operative complication in the >19 million older Americans who undergo surgery each year, and is associated with long term cognitive decline and increased risk for mortality and for the development of Alzheimer’s Disease and Related Dementias. Yet, there are no FDA-approved drugs for preventing or treating delirium, likely because we understand so little of its underlying mechanisms. This grant is based on the central hypothesis that postoperative delirium reflects both an unmasking of prodromal/clinically silent alterations in neuroimmune and brain network function (New Research Project 1), as well as a de novo brain and systemic injury (New Research Project 2). These aims will be carried out via machine learning and artificial intelligence based-analysis of CSF ‘omic measures and functional/structural MRI scans obtained before and after surgery in ~800 older surgical patients from 4 studies conducted by Dr Berger’s team over the last 11 years, all of whom also underwent rigorous cognitive testing and delirium screening before and after surgery. These projects represent a new area of focus for Dr. Berger, whose prior work has mostly focused on postoperative cognitive dysfunction- a syndrome related to but distinct from postoperative delirium. In this K24 grant, Dr Berger will also complete career development activities including didactic courses at Stanford, workshops and 1-on-1 tutorial sessions with leading experts to further his understanding of machine learning/artificial intelligence analysis methods and functional and structural MRI neuroimaging analysis strategies. Dr Berger will mentor his research trainees through Individualized Development Plans (IDPs) that each mentee will create (with input from Dr Berger), regular 1-on-1 mentorship meetings, project meetings, and monthly meetings of SPORT- the Stanford PeriOperative Research Training in delirium program, which features scientific talks by Stanford Anesthesiology investigators who study delirium and by outside invited delirium experts. Dr. Berger’s mentees will include PhD students, MD/PhD students, postdocs, research track residents and junior faculty, who will be supported by three T-level training grants at Stanford Anesthesiology, Dr Berger’s own multiple NIH R level grants, his startup research package from Stanford, and numerous internal Stanford pilot and other training grants. Together, this K24 grant will 1) enable Dr. Berger and his team to conduct two new research projects on postoperative delirium mechanisms, 2) allow Dr. Berger to complete career development activities to learn about and apply modern machine learning/artificial intelligence and functional/structural MRI analysis methods to these research projects, and 3) protect Dr. Berger’s time to continue his outstanding record of mentoring research trainees.
