Cortical Hemodynamism and Oxygenation During Sleep and Cognition: Window to Cognitive Impairment and Neurodegeneration in Aging

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Project Summary My long-term goal is to become a leading physician-scientist in the field of “sleep medicine in aging and neurodegenerative disorders.” Specifically, I aim to become a leading expert in developing innovative methods for sleep and sleep-disordered breathing (SDB) evaluation and concomitant cognition in older adults in order to better understand neurodegenerative disorders. The proposed investigation of sleep, SDB and cognition in older adults will be the basis for my career development as a physician scientist. Sleep and SDB are under-characterized in older adults, particularly in the context of the progression from normal aging to Mild Cognitive Impairment (MCI) to dementia. This is partially because current assessments of sleep are limited due to the lack of information regarding cortical hemodynamism or oxygenation to capture sleep fragmentation or cortical hypoxia from SDB. Thus, simultaneous and synchronized recording of functional neuroimaging monitoring cortical hemodynamism and oxygenation with PSG would substantially contribute to our understanding of the effect of aging on sleep and its subsequent impact on cognitive decline and/or neurodegeneration. Newer technologies such as Near Infrared Spectroscopy (NIRS) have the potential to significantly improve the ability to acquire simultaneous synchronized recording of brain hemodynamism and oxygenation with PSG in order to better understand the aging effects on brain function during sleep and SDB. The project I propose will be to conduct simultaneous NIRS and PSG during sleep, and cognitive tests on older adults with SDB and without SDB. I aim to identify potential sleep biomarkers in hemodynamism or oxygenation patterns from SDB and sleep itself, which will form the basis for my future longitudinal study to examine the extent to which sleep architecture and associated brain function can serve as potent predictors of cognitive decline, MCI and neurodegenerative disorders. Building on my prior training as a Sleep MD and Neurologist, my career development plan is to gain the necessary additional skills to achieve this career goal. My mentorship team will guide my training in 1) combining NIRS with PSG to assess the brain function underlying sleep; 2) other modalities of functional neuroimaging; 3) analysis of functional neuroimaging technologies; 4) characterizing cognitive function, MCI and dementia; 5) understanding the pathophysiology of neurodegenerative disorders and associated comorbidities; and 6) methodological and statistical approaches to cross-sectional and longitudinal data, and analysis of medical/psychiatric comorbidities and medications that impact sleep and aging.