# Cognition and the immunology of postoperative outcomes

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $270,818

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Culley, Deborah J
ABSTRACT
Surgery triggers a cascade of humoral, cellular, and subcellular events involved in inflammation and its
resolution. These profound immune responses have a major influence on postoperative outcomes, and many
complications of surgery are due to dysregulated inflammation. Older persons have more surgery than younger
ones and are especially prone to serious postoperative morbidity. The immune system becomes dysregulated
with age and this dysfunction contributes to the pathogenesis of age-related diseases, including cognitive
decline. Poor cognition is a potent and consistent risk factor for adverse surgical outcomes; we have shown it
doubles the risk of postoperative delirium and halves the chance of being discharged home after elective joint
replacement surgery. We have also demonstrated that between 22-40% of elective surgical patients ≥ 70 years
of age are probably cognitively impaired at the time of surgery. Therefore, the combination of poor preoperative
cognition and poor surgical outcomes is both common and clinically important. Yet, it is not known how poor
cognition increases susceptibility to postoperative morbidity, and the situation is little studied. We propose that
poor preoperative cognition signifies a state of immune disequilibrium / dysfunction that shapes the immune
response to surgery and increases postoperative morbidity. We will test this proposition by examining humoral
(plasma inflammatory and resolution mediators; Aim 1), cellular (monocyte transcriptome and function; Aim 2),
and subcellular (circulating extracellular vesicle [EV] concentration, cargo, and function; Aim 3) components of
inflammation in cognitively screened patients having surgical procedures common in old age (total joint
replacement; spine surgery), with delirium and discharge to place other than home as clinical and patient-
centered-outcomes, respectively. Preliminary results showing cognition- or outcome-related differences in the
ratio of circulating proinflammatory and proresolution mediators, the transcriptome of blood-borne monocytes,
and the distribution of plasma extracellular vesicles support our model. This research is innovative because the
impact of preoperative cognition on the immunology of surgical recovery has not been studied previously, it will
test novel pathogenic mechanisms (monocyte dysfunction, EVs) for preoperative cognition-driven risk and use
state-of-the-art ex vivo and in vitro methods (multiplexed gene panels), and may identify a molecular signature
for adverse postoperative outcomes and, thereby, potential therapeutic targets. Given the magnitude and
importance of the clinical problem being addressed, this is a high impact proposal that may increase the
precision and personalization of surgical care and improve outcomes for older patients.
OMB No. 0925-0001/0002 (Rev. 03/16 Approved Through 10/31/2018) Page Continuation Format Page

## Key facts

- **NIH application ID:** 9983732
- **Project number:** 5R01GM132668-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** DEBORAH J CULLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $270,818
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983732

## Citation

> US National Institutes of Health, RePORTER application 9983732, Cognition and the immunology of postoperative outcomes (5R01GM132668-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9983732. Licensed CC0.

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