# Delirium Dynamics: Understanding Causes and Effects

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $812,175

## Abstract

Project Summary / Abstract
Delirium is an acute disturbance of attention and awareness that afflicts >20% of hospitalized older adults and
costs up to $152 billion each year due to associations with prolonged hospitalization, cognitive decline, and an
accelerated course of dementia and Alzheimer’s disease. Delirium is especially challenging to evaluate and
treat because it is dynamic: patients fluctuate between severe symptoms one hour to minimal the next,
exposing a knowledge gap: we do not know which factors mediate those fluctuations. Many delirium risk
factors, such as age, are irreversible and do not explain delirium’s dynamic course. In contrast, sleep-wake
activity and circadian rhythms are highly dynamic and potentially modifiable. While the incidences of sleep
disturbance and delirium are generally associated, whether and how they interact remains unclear, and clinical
trials targeting sleep do not consistently improve delirium. There is a critical need to determine the sequence of
events through which specific disturbances of sleep-wake activity impact delirium’s trajectory. These efforts
have been limited by a lack of tools to measure delirium and sleep-wake activity continuously. The long-term
goal of this project is to identify new delirium treatments by understanding the characteristics, causes, and
effects of delirium fluctuations. The current objective is to apply novel continuous monitoring to test the central
hypothesis that specific sleep-wake and circadian features predict acute delirium fluctuations, which in turn
forecast long-term cognitive decline. The rationale for the proposed work is that continuous monitoring of
delirium and sleep-wake activity will identify specific disturbances in sleep-wake and circadian activity that
impact delirium’s trajectory, sharpening focus on those specific disturbances to manage delirium acutely. This
project utilizes an innovative approach that integrates recently developed measures of physiologic delirium
severity, sleep-wake activity, and circadian rhythms with artificial intelligence (AI) algorithms to quantify the
course of delirium rigorously. These measures will be used to study the acute course and long-term trajectory
of delirium in 400 hospitalized, non-intubated adults aged 65 years or older, admitted to the hospital with
pneumonia, one of the most common causes of delirium in older adults. Aim 1 will establish the temporal
characteristics of delirium using EEG in hospitalized older adults. Aim 2 will determine which features of sleep-
wake activity affect the subsequent course of delirium. Aim 3 will identify the features of acute delirium
trajectories that predict long-term cognitive impairment. The proposed research is significant because it will
lead to the following expected outcomes: (1) new methods to quantify and track delirium severity at the
bedside, (2) identification of specific sleep, circadian biology, and environmental factors as therapeutic targets
to improve deli...

## Key facts

- **NIH application ID:** 10804256
- **Project number:** 1R01AG078261-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Eyal Yaacov Kimchi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $812,175
- **Award type:** 1
- **Project period:** 2024-05-15 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10804256

## Citation

> US National Institutes of Health, RePORTER application 10804256, Delirium Dynamics: Understanding Causes and Effects (1R01AG078261-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10804256. Licensed CC0.

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