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Acoustic Enhancement of Sleep: A Tool to Boost Sleep-Mediated Benefits on Memory and Autonomic Nervous System Functions in Aging

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Slow-wave sleep (SWS) is important for overall health since it affects many physiological pathways from cardio-metabolic health to cognitive function. Sleep and autonomic nervous system (ANS) functioning are closely coupled at anatomical and physiological levels. Sleep-related changes in ANS function are likely the main pathway through which SWS affects many systems within the brain and body. Sleep and ANS activity fluctuate in a synchronized manner such that parasympathetic function is highest during SWS. Furthermore, SWS is known to be particularly conducive to hippocampal-dependent memory consolidation. Recently, the ANS has also been implicated in contributing to sleep-mediated benefits on memory consolidation. However, the exact relationship between sleep, the ANS, and memory in young healthy individuals is not well understood, let alone in the context of aging and cognitive decline. SWS and slow wave activity (SWA), the electroencephalographic (EEG) quantification of SWS in the 0.5 to 4 Hz frequency band, decline with aging. They are further reduced in patients with amnestic Mild Cognitive Impairment (aMCI), a condition associated with high risk for developing Alzheimer’s dementia. Autonomic function is also impaired in aMCI and is considered a risk factor for progression to AD. A decline in SWA may contribute to hippocampal-based memory impairment in older adults as well as individuals with aMCI. Therefore, effective interventions to enhance SWA may prove useful as a therapeutic tool to improve age-related and disease-related memory decline. Experimental manipulations that enhance SWA can improve sleep-mediated memory and immune function in young adults. However, the effects of SWA enhancement on the ANS, with specific implications for memory, have not been investigated across multiple age groups. In this thesis, an adaptive algorithm was employed to deliver 50-ms bursts of sound phase-locked to slow-waves during sleep, with regular pauses in stimulation (~5-s ON/~ 5-s OFF), in (1) healthy young adults, (2) healthy older adults, and (3) individuals with aMCI. This thesis sought to determine whether acoustic enhancement of SWA altered ANS function during SWS and the impact of sleep and ANS alterations on overnight memory consolidation. Furthermore, this thesis sought to investigate the ability of acoustic stimuli to increase SWA in aging populations both with and without cognitive decline, and what impact the SWA enhancement had on memory consolidation in older age. The overarching hypothesis of this thesis is that though sleep changes with age, it remains plastic and susceptible to modulation. Such modulation has cascading impact on other sleep-dependent processes, such as learning and memory and autonomic nervous system function. The sleep system continues to interact dynamically with peripheral physiology. It also plays an important role in sleep-dependent memory consolidation, even in the presence of cognitive decline and structural atrophy associated with aging. The studies in this thesis aim to test the ability to modulate sleep in a non-invasive fashion. Furthermore, they aim to understand the impact rhythmic acoustic stimulation can have on the brain and the potential mechanisms by which this tool can benefit sleep function. The findings from these studies open up new questions about brain physiology during sleep and suggest future pathways of disease-related intervention across age.

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