Sleep, breathing, hemodynamic oscillations, and cerebrospinal fluid movements - Building toward a novel treatment approach for Alzheimer's disease

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Sleep, breathing, hemodynamic oscillations, and cerebrospinal fluid movements – Building toward a novel treatment approach for Alzheimer's disease Sleep deficiencies/problems are common in Alzheimer's disease with several hypothesized connections to the movement of cerebral spinal fluid (CSF) in the brain. For example, within Alzheimer's disease the accumulation of beta-amyloid and tau proteins may reflect inefficiencies in neuro-metabolic waste clearance during sleep (a glymphatic system process that is intricately linked with CSF movement). Within neurodegenerative research, the circulation of CSF has hypothesized links to several biological/physiological processes (e.g., sleep, hemodynamic oscillations, breathing); however, we are limited in our understanding of how to potentially improve CSF movement and neuro-metabolic waste clearance to ultimately slow the progression of Alzheimer's disease. The present study fills these critical gaps by (1) quantifying sleep-coupled CSF movement and (2) documenting how CSF movement is coupled with other (more easily assessed and manipulated) biological signals (i.e., hemodynamic oscillations, breathing). The overarching goals of this line of work are to improve our understanding of CSF movement and how this knowledge can be leveraged to slow the progression of Alzheimer's disease. Unlike blood circulation, CSF has no `engine' to drive its flow; therefore, changes in cerebral blood volume (CBV) likely serve as a `driver' of CSF movement. Previous research demonstrates that increases in CBV can be neuronally driven (e.g., sleep); arterial pulsation driven; or breath driven (e.g., meditation/guided breathing). However, we do not understand the magnitude of these changes/couplings. Improving CSF movement/circulation for individuals with Alzheimer's disease has the potential to slow the pathology progression and could prolong higher quality of life for the millions of Americans currently diagnosed.  Aim 1: Assess the degree of coupling between cerebral blood volume (CBV) and cerebral spinal fluid (CSF) movement during wake and sleep states.  Aim 2: Assess the relative contributions of breathing oscillations on CBV and CSF fluctuations during wake and sleep states.