# Epigenetic Changes and Delirium After Intensive Care Unit Admission

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $195,625

## Abstract

PROJECT SUMMARY/ABSTRACT
Intensive care provides lifesaving monitoring and intervention. However, extensive literature reports that
intensive care unit (ICU) survivors, particularly older patients, too often experience significant deficits following
discharge that impair quality of life for at least 1 year after discharge. Delirium, which presents in 30-80% of
ICU patients depending upon specific population, has been associated with worse outcomes, including
cognitive dysfunction and progression to dementia, and therefore has been a focus of intervention studies to
improve ICU survivor outcomes. The majority of these studies focus on two areas- modifying the sedation
regime and promoting early mobility. While important, these studies do not target the underlying mechanism
that leads to delirium. The pathophysiologic underpinnings of delirium are not well understood and there are no
known efficacious treatments.
This proposal focuses on increasing understanding of the complex pathophysiologic mechanisms, and
specifically persistent inflammation, contributing to ICU delirium and the individual variability contributing to this
process. While all ICU patients are at risk, not all individuals experience ICU delirium and older individuals are
more likely to develop delirium. Identifying mechanisms that contribute to delirium can provide information
crucial to decreasing its’ frequency and improving the poor outcomes in ICU survivors. We hypothesize that
there is variable inflammatory gene methylation during critical illness influenced by age, sex and medical
condition and, in addition, distinct inflammatory gene methylation profiles characteristic to patients who develop
ICU delirium. Identification of these profiles will clarify time dependent changes in inflammatory status
important for brain function. The aims of this project will identify changes in inflammatory gene methylation
during the first 7 days after ICU admission in subjects of different age and sex and with different medical
diagnoses, as well as the specific changes occurring before and during ICU delirium, while controlling for
relevant cell counts. Additionally we will quantify gene product (protein) in serum of a subset of the population
to explore the relationship between inflammatory gene methylation and associated inflammatory proteins. This
project capitalizes on the experience and expertise of a multi-disciplinary investigative team including
representation from the fields of nursing, genetics, neuropsychology, statistics and critical care medicine. The
overall goal of this project is to clarify one possible source of genetic variability contributing to a persistent
inflammatory state common in delirium in ICU patients.

## Key facts

- **NIH application ID:** 9998817
- **Project number:** 5R21AG059167-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** SHEILA A ALEXANDER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,625
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998817

## Citation

> US National Institutes of Health, RePORTER application 9998817, Epigenetic Changes and Delirium After Intensive Care Unit Admission (5R21AG059167-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9998817. Licensed CC0.

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