# The Association of Blood-Brain Barrier Breakdown with Sleep Apnea and Postoperative Delirium

> **NIH NIH R03** · DUKE UNIVERSITY · 2021 · $161,000

## Abstract

ABSTRACT
Blood-brain barrier (BBB) breakdown occurs in older patients after anesthesia/surgery, and could
increase risk for postoperative delirium. BBB breakdown could play a role in postoperative delirium
because 1) anesthesia/surgery are associated with BBB breakdown and 2) BBB breakdown is
associated with neuroinflammation, which has been linked to delirium and Alzheimer’s disease (AD).
The BBB, which normally restricts diffusion of large molecules into the central nervous system, can be
assessed by measuring large molecules, such as albumin, in the cerebrospinal (CSF). BBB breakdown
results in an increased CSF-to-serum ratio of albumin (Qalbumin). Increased Qalbumin is associated
with neuroinflammation, increased AD risk, and accelerated cognitive decline. Although BBB
breakdown is theorized to play a role in postoperative delirium, no studies have yet determined whether
postoperative delirium is associated with BBB breakdown (ie, increased Qalbumin).
 One potentially modifiable risk factor for BBB breakdown is obstructive sleep apnea (OSA),
characterized by repeated interruptions in breathing during sleep, that is associated with postoperative
delirium, mild cognitive impairment, and accelerated AD pathology. Since OSA is a frequently
undiagnosed, highly prevalent (~50% of older adults) disorder, OSA could represent a pervasive, yet
treatable, risk factor for BBB breakdown.Thus, we will also determine whether OSA patients have
increased preoperative BBB breakdown (ie, Qalbumin), which could potentially predispose OSA
patients to postoperative delirium.
 The overall aim of this study is to measure the magnitude of blood-brain barrier (BBB) breakdown
in older adults undergoing non-cardiac surgery, and determine the extent that BBB breakdown is
associated with OSA and postoperative delirium severity. To test these hypotheses, I will prospectively
study 200 non-cardiac surgery patients over age 60 from my ongoing foundation-funded study: Sleep
Apnea, Neuroinflammation, and cognitive Dysfunction Manifesting After Non-cardiac surgery
(SANDMAN), and my mentor’s larger NIA K76-funded study. These patients already undergo
preoperative OSA testing, pre- and postoperative blood/CSF sampling, and delirium assessment.
Leveraging this unique, existing cohort and cerebrospinal fluid samples makes these proposed studies
feasible as all the samples will already be collected by the anticipated grant period. Our findings will
help us understand mechanisms of OSA-related neurocognitive dysfunction, and eventually inform the
development of therapies to reduce postoperative delirium and to help prevent AD for >16 million older
Americans who undergo surgery every year

## Key facts

- **NIH application ID:** 10302785
- **Project number:** 1R03AG067976-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Michael Joseph Devinney
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $161,000
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302785

## Citation

> US National Institutes of Health, RePORTER application 10302785, The Association of Blood-Brain Barrier Breakdown with Sleep Apnea and Postoperative Delirium (1R03AG067976-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10302785. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*