Noninvasive Quantification of Age-Related Alterations in Sleep-Dependent CMRO2 Attenuation Using EEG-Correlated MRI

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Project Summary A significant fraction of the US population suffers from various degrees of insomnia, conditions particularly prevalent in the elderly. Fractured sleep has adverse effects on cognitive function and memory, and may contribute to age-related cognitive decline. The brain is a highly metabolic organ, but during slow-wave sleep, cerebral glucose and oxygen metabolism decline. This reduction in brain metabolism may be critical for long-term homeostasis, while an inability to adequately lower brain energy expenditure during sleep may lead to oxidative injury. Prior work examining alterations in brain metabolism during slow-wave sleep relied on invasive methods. We have, in preliminary work, developed a noninvasive MRI-based method, termed OxFlow, to noninvasively quantify the cerebral metabolic rate of oxygen consumption (CMRO2) at a tem- poral resolution of seconds, along with concurrent, in-scanner EEG monitoring. OxFlow quantifies CMRO2 via Fick's principle using concurrent measurement of venous O2 saturation and total brain cerebral blood flow (tCBF). The approach's feasibility has been demonstrated in test subjects in whom neurometabolic pa- rameters were measured during wakefulness and sleep. In Aim 1 of this project we propose to further de- velop the OxFlow method for use in sleep research. Specifically, we will modify the gradient structure to at- tenuate acoustic noise so as to facilitate subjects' ability to initiate and maintain sleep. We will also optimize EEG filtering procedures to minimize interference of MRI gradient-induced electronic noise to reliably allow simultaneous EEG recordings needed as a means to establish the subject's stage of consciousness. In Aim 2 we will test the hypothesis that in older subjects, slow-wave sleep is associated with a reduced awake-to- sleep decrement in CMRO2 as compared to younger subjects. We will address this hypothesis by subjecting 12 young and 12 older subjects (25-40 vs. 60-80 years) to a combined MRI/EEG sleep protocol. This study will provide new noninvasive methods for measuring sleep dependent brain energy regulation and begin to demonstrate its utility in research on brain aging and dementia.