# Characterizing the Relationship between Brain Electrophysiology, Delirium, and Cognitive Decline

> **NIH NIH P01** · HEBREW REHABILITATION CENTER FOR AGED · 2021 · $360,154

## Abstract

ABSTRACT 
Delirium is a common and costly problem, affecting up to half of hospitalized older adults, and resulting in 
substantial morbidity, cognitive decline, loss of functional independence, and increased mortality. Delirium is 
particularly problematic in patients with Alzheimer's dementia who have an increased risk for delirium, and in 
whom delirium accelerates the rate of cognitive decline. However, our understanding of the neurological basis 
of the risk for and effects of delirium in a given individual remains very limited. This project seeks to address 
this important knowledge gap by utilizing magnetic resonance imaging (MRI)-guided (neuronavigated) 
transcranial magnetic stimulation (TMS) with simultaneous electroencephalography (EEG) and 
electromyography (EMG) to evaluate cortical function in patients undergoing elective surgery. In a prospective 
cohort of 180 patients we will examine whether decreased brain network connectivity and altered mechanisms of 
cortical plasticity as characterized by TMS-EEG-EMG are associated with the risk of developing post-operative 
delirium. We will record TMS-evoked potentials (TEP) from dorsolateral prefrontal cortex, inferior parietal 
lobule, and primary motor cortex, before and after intermittent theta-burst stimulation (iTBS). We hypothesize 
that baseline EEG spectral power and connectivity, TMS-based measures of cortical reactivity and 
connectivity, and iTBS measures of cortical plasticity will be decreased in patients who subsequently develop 
delirium, and that patients with greater abnormalities in EEG features and TMS measures at baseline will have 
greater delirium severity and greater short-term cognitive decline after an episode of delirium. We will correlate 
neurophysiologic measures with changes in cognitive performance and subsequent cognitive decline in patients 
with versus without delirium. We hypothesize that EEG alpha power and connectivity, TMS reactivity, TEP 
cortical connectivity, and efficacy of the mechanisms of cortical plasticity will show greater decreases in 
patients with delirium than in those without, and will correlate with the magnitude of cognitive decline. Finally, in 
patients with a previously observed episode of delirium (in SAGES I) we will compare those with and without a 
history of delirium, and hypothesize that cortical physiology abnormalities will correlate with long-term cognitive 
decline after delirium (complicated delirium). Ultimately, our results will define neurophysiologic characteristics 
that can identify individuals with a vulnerable brain susceptible to delirium and subsequent cognitive decline, 
will provide novel tools to efficiently assess the effectiveness of interventions to help increase individual 
cerebral resilience and reduce the risk of delirium, and will guide development of therapeutic interventions to 
help normalize cerebral dysfunction and minimize long-term cognitive decline after delirium.

## Key facts

- **NIH application ID:** 10168403
- **Project number:** 5P01AG031720-09
- **Recipient organization:** HEBREW REHABILITATION CENTER FOR AGED
- **Principal Investigator:** Alvaro Pascual-Leone
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $360,154
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168403

## Citation

> US National Institutes of Health, RePORTER application 10168403, Characterizing the Relationship between Brain Electrophysiology, Delirium, and Cognitive Decline (5P01AG031720-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10168403. Licensed CC0.

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