# A Breakdown of Memory Replay: Elucidating the Relationship Between Sleep and Alzheimer's Disease from Surface Electroencephalography

> **NIH NIH R03** · UNIVERSITY OF COLORADO DENVER · 2024 · $155,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer's disease is a leading cause of death in the U.S., and its prevalence is expected to climb from nearly
6 million today to 13 million Americans by 2050. Sleep disruption is known to be a risk factor for age-associated
cognitive decline and for the development of Alzheimer's disease. Efforts to understand the connections between
sleep and Alzheimer's disease have focused on key neuroprotective aspects of slow wave sleep, including its
role in memory processing via regulation of synaptic remodeling and restoration of synaptic homeostasis. A
critical process in sleep's memory functions is a form of memory replay, during which sequences of neuronal
activity repeat and reproduce patterns that mirror the wake state of memory. My research team has focused on
the identification of the neuronal communication elements that constitute memory replay, and several of these
elements are observable from simple surface electroencephalography (EEG). Slow waves, theta bursts, and
sleep spindles mark the timing of memory replay cycles, and understanding their role in cognitive aging and
Alzheimer's disease may offer a novel method to detect and/or predict neurodegenerative disease, as well as
provide a target for efforts to restore the neuroprotective properties of sleep. Our preliminary results suggest that
changes in theta bursts are associated with cognitive decline among aging adults and may also predict future
decline. My overall goal is to fill knowledge gaps in the connections between memory replay of sleep and
Alzheimer's disease pathogenesis to help guide the development of novel diagnostics and interventional
approaches for Alzheimer's disease. My overarching hypothesis is that changes in theta burst EEG power are
associated with cognitive decline among aging adults. My research objectives are to determine the relationships
between theta burst EEG power and cognitive changes in the context of age-associated cognitive decline as the
basis for future biomarker development and causation/mechanistic studies in early Alzheimer's disease. I will
accomplish these objectives by pursuing the following Specific Aims: Aim 1a) Determine whether changes in
theta burst power occur in aging adults who experience cognitive decline, Aim 1b) Determine whether changes
in cognitive scores and baseline theta burst power among aging adults serve as an effective predictor of future
cognitive decline, and Aim 2) Determine the contribution of theta burst size and theta burst temporal alignment
to the reductions in observed theta burst EEG power. My proposed experiments are innovative because they
are the first to examine the relationships between theta burst changes and cognitive aging. My proposal is
significant because it will further our understanding of the neuroprotective properties of sleep and will advance
a clinical tool that may measure the integrity of critical neuronal functions as a biomarker and treatment target.

## Key facts

- **NIH application ID:** 10843761
- **Project number:** 5R03AG080427-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Brice V McConnell
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $155,500
- **Award type:** 5
- **Project period:** 2023-06-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843761

## Citation

> US National Institutes of Health, RePORTER application 10843761, A Breakdown of Memory Replay: Elucidating the Relationship Between Sleep and Alzheimer's Disease from Surface Electroencephalography (5R03AG080427-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10843761. Licensed CC0.

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