Determining the Optimal Sleep Pattern to Promote Glymphatic Clearance of Amyloid-Beta in Individuals at Risk for Alzheimer's Disease: A Research Protocol

Abstract

Introduction: Neurodegenerative disorders such as Alzheimer’s disease (AD) are increasingly prevalent amongst older populations. Sleep irregularities are one of the chief complaints in people diagnosed with sleep disorders. Sleep has been hypothesized to ensure metabolic homeostasis and remove neurotoxic waste. Inadequate sleep leads to an accumulation of Amyloid-Beta (Aβ) levels which is associated with neurodegenerative diseases including AD and other dementias. Sleep is the driver of the glymphatic system, located in the perivascular space. The glymphatic system eliminates soluble proteins, including Aβ, from the central nervous system; transporting cerebrospinal fluid through the brain; and distributing macromolecules across the brain. This research proposal aims to identify optimal sleep patterns that decrease neurodegeneration by increasing glymphatic system functioning. Methods: This study will be an ad-hoc study conducted over a 6-month period utilizing participants who have reported a family history of AD. Aß accumulation and cortisol levels will be measured to identify signs of neurodegeneration using brain scans, such as Positron Emission Tomography, and blood tests. Other parameters such as memory, energy rating, and sleep latency will be measured. Results: Reduced slow-wave sleep may lead to a disruption in the glymphatic system. Monophasic sleep is said to have the most slow-wave sleep, and least rapid eye movement sleep which is most similar to wakefulness. Therefore, we hypothesize that monophasic sleep will slow neurodegeneration compared to biphasic and polyphasic sleep, contrary to popular belief that biphasic sleep is more beneficial than monophasic sleep. Discussion: In this experiment, we expect to see increased glymphatic clearance after monophasic sleep. There are many factors that can impact sleep patterns and glymphatic clearance including work style, environment, culture, race, sex, and genetic markers for AD. Conclusion: Further research that applies this suggested methodology should account for these variabilities when making conclusions on the optimal sleep pattern for plaque clearance in the brain. This proposal may improve research on AD by identifying the effects different sleep patterns have on the brain and neurodegeneration. Future research may study changes in sleep habits as a preventative measure for individuals who are at risk for or have been diagnosed with AD.