# Blood Brain Barrier Dysfunction and Perioperative Neurocognitive Disorders in older adults

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $429,000

## Abstract

PROJECT SUMMARY/ABSTRACT
 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
(S100β 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 m...

## Key facts

- **NIH application ID:** 10108141
- **Project number:** 1R21AG070269-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Rajesh Kumar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2020-09-11 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108141

## Citation

> US National Institutes of Health, RePORTER application 10108141, Blood Brain Barrier Dysfunction and Perioperative Neurocognitive Disorders in older adults (1R21AG070269-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10108141. Licensed CC0.

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