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

项目总结/文摘

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.