Graduation Date

Spring 5-10-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Neuroscience

First Advisor

Tony W. Wilson

Second Advisor

Pamela E. May-Weeks

Abstract

There has been a significant shift in the demographics of the United States towards an older populace, which has been accompanied by an increase in the prevalence of age-related neurodegenerative disorders, including Alzheimer’s disease (AD). A major component of AD-related cognitive impairment is attention deficits. While alterations of neurophysiological activity are well-documented in other domains, those which underlie the observed attentional deficits are less understood. Moreover, sleep disruptions are a common comorbidity of AD and sleep has been proven to be a modifiable risk factor in the development of AD. Sleep disruptions may contribute to the development and more rapid progression of cognitive decline in AD, including attention deficits, but these factors are understudied, and the key neurophysiological features of these comorbidities remain unknown. The studies reported herein aim to fill this knowledge gap by integrating cutting-edge multimodal brain mapping methods, with neuropsychological testing and subjective and objective sleep measures to quantify spontaneous neural activity during the resting-state and the neural dynamics underlying visual attention. Our primary goals were to determine how these neural indices were related to sleep disturbances and amyloid-beta protein deposition in the context of AD. Overall, we observed aberrant multi-spectral cortical oscillations in individuals on the AD spectrum. These aberrations were related to cognitive deficits, subjective and objective sleep measurements, and regional pathological protein deposition. Specifically in Chapter 1, we show that sleep is tightly related to spontaneous neural activity in patients on the AD spectrum and associated with cognitive function and regional amyloid accumulation. In Chapter 2, we demonstrate that neural oscillations important for visual attention are modulated by AD and that attention-related oscillations differentially predict neuropsychological outcomes in patients on the AD spectrum compared to cognitively-normal older adults. Finally, in Chapter 3 we examine the relationship between objective sleep metrics and neural oscillations during an attention task, as well as how sleep hygiene together with neural activity relates to cognitive outcomes. Altogether, our results show that AD strongly modulates neural oscillatory activity and support a mechanistic role for sleep disturbances in the widely reported neurophysiological aberrations seen in patients on the AD spectrum. Our primary findings help further the field’s understanding of the complex interactions between sleep quality, AD-related pathologies, and cognitive function, and suggest that sleep should be a major focus of future research, as it could be a potentially pivotal modifiable risk factor in AD.

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