# Circadian Multiscale Activity Regulation and the Risk for Delirium in Elderly Hospitalized Patients

> **NIH NIH R03** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $134,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Developing effective interventions for delirium in the elderly urgently requires a better understanding of
modifiable risk factors and underlying mechanisms in earlier life. There is evidence that alterations in the ~24-
hour sleep/wake cycle, known as circadian rhythms, coincide with the development of delirium. Disturbances in
circadian rhythm and sleep are more common in the elderly, in neurodegenerative diseases such as Alzheimer’s
dementia, and become more pronounced after critical illness. Inflammatory changes have been shown after
circadian/sleep disruption, while conditions associated with delirium often involve high inflammatory states. This
project hypothesizes that earlier life circadian/sleep regulation predicts incident delirium after hospitalization, and
that systemic inflammatory burden underlies this link. We propose the analysis of rest/activity data collected from
wearable technology (actigraphy watches), repeated serum high-sensitivity (hs-CRP) and insulin-like growth
factor-1 (IGF-1) measurements and genetic data in middle/elderly age subjects from the UK Biobank, a unique
database of ~500,000 subjects aged between 40-69 years who were recruited between 2006 and 2010, and
agreed to have their health followed. Normalized 24h amplitude, acrophase of daily activity rhythm, inter-daily
stability (IS), intra-daily variability (IV) and fractal scaling property (α) will be derived from actigraphy as measures
for circadian multiscale activity regulation (CMAR), as well as quantitative sleep measures (sleep fragmentation
index, sleep efficiency and total sleep duration), in ~96,600 subjects from the UK Biobank. In those who become
hospitalized/undergo surgery, we will test whether CMAR/sleep measures independently predict incident
delirium, and how they augment the effects of cognition and aging on delirium risk (Aim 1). Relationships
between CMAR/sleep measures, systemic inflammation and delirium will be studied by examining the
associations between baseline and change in hs-CRP and IGF-1 over two visits, and later risk for delirium, as
well as the associations between CMAR/sleep measures and baseline inflammation and (Aim 2). Mendelian
randomization (MR) will be used to test whether recently discovered genetic variants of circadian/sleep
disturbances and established genetic variants of the CRP gene are causally related to delirium. Genetic variants
associated with delirium will be explored using a Genome-wide association study (GWAS) (Exploratory Aim 3).
Taken together, the proposed three aims may provide modifiable, objective measures of delirium risk, expand
on our knowledge of delirium pathophysiology, and lead to novel genetic insights into how circadian/sleep
regulation and inflammation influence future delirium vulnerability.

## Key facts

- **NIH application ID:** 10027773
- **Project number:** 1R03AG067985-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Lei Gao
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $134,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10027773

## Citation

> US National Institutes of Health, RePORTER application 10027773, Circadian Multiscale Activity Regulation and the Risk for Delirium in Elderly Hospitalized Patients (1R03AG067985-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10027773. Licensed CC0.

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