Breathing therapy to improve clearance of brain toxins in elder poor sleepers
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Clearance of the brain metabolic waste products is a critical function of sleep. It is well established that toxins linked to Alzheimer’s disease (AD) are elevated in elder poor sleepers compared to good sleepers, most likely due to impaired clearance, yet the mechanism linking poor sleep with toxins accumulation and accelerated neurodegeneration is not fully understood. Current studies on impaired clearance of toxins during sleep focus on the cranial pathways of toxins clearance, i.e., the traditional pathway, namely CSF absorption into the superior sagittal sinus, and the more recently discovered pathways, the meningeal lymphatics and the glymphatic systems. The efflux of amyloid beta (Aβ) from the glymphatic system across the blood brain barrier (BBB) is carried by specific transporters whose expression decreases with age, which contributes to the buildup of Aβ in the aging brain. In contrast, studies focusing on clearance of toxins through spinal pathways are sparse. Our lab proposed the existence of a spinal pathway that is most effective during deep sleep. In this pathway, soluble toxins in the cranial CSF are transferred to the CSF in the spinal canal. In humans, between one and two thirds of total CSF formation are cleared to the blood by the spinal CSF absorption sites. Therefore, transferring toxins from the toxin-rich cranial CSF to the spinal CSF augments overall toxin clearance. The transfer of toxins to the spinal CSF is driven by CSF oscillations between the cranium and spinal canal. Breathing influences the craniospinal (cs)CSF oscillations, and thereby, breathing patterns determine the level of the toxin clearance through this pathway. Using real-time velocity encoding MRI, our lab found that during slow abdominal breathing (SAB), which approximates breathing during deep sleep, the csCSF volume displaced to-and-from the spinal canal is over 50% larger compared to breathing during the awake state. These finding supports the hypothesis that toxin clearance can be augmented by manipulation of breathing. Thus, our goal is to demonstrate the feasibility of a breathing-based therapy to augment toxins clearance in elderly poor sleepers. The proposed research is significant because it addresses a knowledge gap in the role of the csCSF oscillations in the clearance of toxins during sleep, and it addresses a critical need for a noninvasive therapy which negates the ill effect of poor sleep on the brain. The proposed therapy applies modified positive airways pressure (PAP) to manipulate the breathing such that toxins clearance is significantly enhanced. PAP therapy is safe and is already widely used to treat obstructive sleep apnea (OSA). The availability of PAP devices will fast track the implementation of a new therapy for the treatment of non-OSA elderly poor sleepers who are at elevated risk for developing AD. Since poor sleep is widespread in the elderly, the proposed therapy is timely and could become an important tool in the armament available to combat cognitive decline and AD dementia in elderly poor sleepers.
