# Clarifying the overlapping pathology of delirium and dementia

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $769,730

## Abstract

Project Summary/Abstract
Dementia is the sixth leading cause of death in the United States and is associated with loss of quality of life and
independence; it cannot be prevented, cured, or even slowed. Delirium is a sudden state of confusion that is
associated with increased morbidity and mortality and impaired long-term cognition. Although there are
substantial costs to both conditions – financial, societal and individual – delirium and dementia are bereft of
therapies, largely due to the limited understanding of their pathogeneses. The bidirectional predisposition of
dementia and delirium to each other offers a unique opportunity to understand their overlapping pathological
mechanisms and to identify new therapeutic approaches. For example, predisposition to delirium and dementia,
denoted by amyloid deposition, is associated with increased frontal alpha power, suggesting that similar changes
in brain dynamics are evident before the onset of either condition. Cortical slow wave activity (SWA) is a shared
electrophysiological hallmark of cognitive changes in aging, delirium and dementia. We propose that
understanding SWA in wakefulness, which affects all these conditions, will lead to novel, mutually informative
insights into the pathogenesis of those conditions. Our overarching hypothesis is that delirium results from
an interaction between inflammation and two key dementia pathologies, amyloid and
neurodegeneration, leading to the electrophysiological disturbance of cortical SWA and impaired
connectivity, which results in delirium. In this application, we will test how amyloid and neurodegeneration
predispose to (Specific Aim 1) and are exacerbated by (Specific Aim 3) an episode of delirium. We will also
investigate the mechanistic role of inflammation to induce delirium, SWA, and connectivity changes through
interaction with amyloid pathology and neurodegeneration (Specific Aim 2). In this way, we can understand how
delirium interacts with the trajectory of two dementia pathologies, while understanding how SWA, and therefore
the cognitive changes of delirium, can arise so abruptly. Our technical innovation is to use 256 channel high-
density electroencephalogram (HD-EEG) to track the electrophysiological changes with behavior. We will source
reconstruct the SWA to individual subject anatomy using state-of-the-art electrode digitization to allow
correspondence of the SWA to a subject's magnetic resonance imaging (MRI) or positron emission tomography
(PET) amyloid data. Mapping spatial overlap in pathologies is our methodological innovation, which enhances
biological plausibility for any relationship. We will track how delirium contributes to neuropathological changes
that may account for the cognitive decline after surgery. Our data will illuminate the pathological overlap of
delirium and dementia, highlighting (i) new avenues for screening/novel biomarker endpoints for amyloid
pathology or risk of delirium (frontal alpha power) and (ii) thera...

## Key facts

- **NIH application ID:** 10408717
- **Project number:** 5R01AG063849-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** ROBERT A PEARCE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $769,730
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408717

## Citation

> US National Institutes of Health, RePORTER application 10408717, Clarifying the overlapping pathology of delirium and dementia (5R01AG063849-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10408717. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*