Increasing numbers of older adults are undergoing surgery (~37% of all surgeries), with the primary goal of improving function and quality of life. However, these surgical procedures increase the risk of developing postoperative neurocognitive disorders (PND). PND pose a significant public health problem, leading to a cascade of deleterious complications, including prolonged intensive care and hospital stay, increased healthcare costs (~$150 billion/year), reduced patients? function, and are independently associated with subsequent cognitive impairment and ultimately dementia. Older adults are particularly at-risk of developing PND both in the short and long term. Although age is consistently reported as an important risk factor, the exact pathophysiology of PND remains poorly understood, but may include postsurgery-compromised blood brain barrier (BBB) function. Surgery can disrupt the BBB function via the release of inflammatory mediators that facilitate migration of macrophages and pro-inflammatory cytokines into brain regions. However, clinical reports of links between PND and BBB function, and brain tissue, are scarce and small in number. This project proposes that perioperative BBB disfunction is associated with measurable brain morphologic findings in cognitive control areas that can be discovered with non-invasive magnetic resonance imaging. Patients scheduled for surgery with an age range of 65-75 years of age, will participate in brain diffusion-weighted pseudo-continuous arterial spin labeling and diffusion tensor imaging, cognitive assessment, and evaluation of a BBB marker from blood (at baseline, at two weeks, and at six months after surgery).
The specific aims are to: 1) examine BBB function, using diffusion-weighted pseudo-continuous arterial spin labeling procedures, and BBB marker from blood (S100? levels); 2) assess brain tissue changes, using diffusion tensor imaging-based mean diffusivity measures, and cognition function; 3) examine the relationships between BBB blood biomarker, BBB function index, and mean diffusivity values in cognitive control areas (prefrontal cortex, caudate, and hippocampus). In summary, the overall purpose of this study is to examine the potential mechanisms contributing to PND in an older surgical population, with the hypothesis that BBB will be altered, contributing to brain tissue changes in cognitive control areas, reflected as PND. The proposed study has the potential to dramatically impact clinical practice, benefiting not only older adults undergoing surgery, but also the general surgical population. The successful completion will advance understanding of how surgery affects the blood-brain barrier interface, and will provide new mechanisms of relevance to PND, neurodegeneration, and aging. This study will expand current scientific understanding of PND and provide critical pilot data for future intervention-based studies that can further the development of preventive measures, improving patient outcomes, and greatly impacting the quality of life for millions of older patients in the United States.

Public Health Relevance

Millions of older Americans require common surgical interventions, placing them at risk for developing devastating postoperative neurocognitive disorders. However, the exact pathophysiology of postoperative neurocognitive disorders remains poorly understood, but may include compromised blood brain barrier function induced brain changes. We will examine the potential mechanisms of brain injury contributing to postoperative neurocognitive disorders opening up groundbreaking avenues for future interventions that identify, prevent, and treat these diseases, and thus, reduce morbidity and mortality in older surgical patients.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Aging Systems and Geriatrics Study Section (ASG)
Program Officer
Roberts, Luci
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Schools of Medicine
Los Angeles
United States
Zip Code