# The Role of the Aging Brain-Heart-Immune Axis in Postoperative Delirium

> **NIH NIH R03** · DUKE UNIVERSITY · 2022 · $161,000

## Abstract

ABSTRACT
Postoperative delirium (POD) is a syndrome of acute fluctuating changes in attention and
consciousness that affects up to 50% of surgery patients 65 and older, increases the risk for
Alzheimer's disease (AD) and AD-related dementias (ADRD), and accelerates dementia
progression. Yet, interventions for POD are limited because its pathophysiologic mechanisms are
poorly understood.
The vagus nerve mediates the brain-heart-immune axis, which allows the brain to suppress
systemic inflammation via the cholinergic anti-inflammatory reflex. Advanced age, preoperative
stressors, the condition requiring surgery, and surgery and anesthesia themselves all decrease
vagal tone. Without sufficient vagal tone to keep inflammation in check, excessive inflammation
will result, including neuroinflammation. Excessive postoperative inflammation is thought to play
a role in POD pathogenesis. Furthermore, excessive postoperative inflammation can injure
neurons, providing a plausible mechanistic link between POD and AD+ADRD. Thus, there is a
critical need to evaluate the role of the brain-heart-immune axis in POD among older adults.
To interrogate the aging brain-heart-immune axis as a possible contributor to POD pathogenesis,
heart rate variability (HRV), the standard measure of vagal tone, will be measured before general
surgery in 100 patients 65 and older. Specifically, the prospective, observational HIPPIE - HRV
In POD and Postoperative Inflammatory Endpoints - study will quantify the relationship between
preoperative vagal tone and (1) POD incidence and (2) postoperative increase in serum
biomarkers of inflammation and neuronal injury. Successful completion of the HIPPIE study will
demonstrate the involvement of the brain-heart-immune axis in POD pathogenesis and will
provide novel biomarker(s) of POD risk. Furthermore, a mechanistic link between POD and the
brain-heart-immune axis is anticipated to provide strong scientific justification for future trials of
vagal tone enhancement as an intervention for POD. Finally, this work will provide a rich new
perioperative geriatric data set including measurements of the previously unexplored
perioperative brain-heart-immune axis. The data, experience, and training from this proposal will
lay the foundation of a successful career in geriatrics research.

## Key facts

- **NIH application ID:** 10517672
- **Project number:** 1R03AG078891-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Leah Acker
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $161,000
- **Award type:** 1
- **Project period:** 2022-09-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10517672

## Citation

> US National Institutes of Health, RePORTER application 10517672, The Role of the Aging Brain-Heart-Immune Axis in Postoperative Delirium (1R03AG078891-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10517672. Licensed CC0.

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