Exploring Sleep Disturbance in CNS Disorders*

Presidential Symposium

Date/Time: Sunday, September 10, 2023 - 1:00 PM – 3:00 PM
Track: Plenary
Room: Salons E-F (5th Floor)
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Session Evaluation Form: https://myana.org/form/ana2023-session-evaluation-explo

Chair: Frances E. Jensen, MD, FACP, FANA

Co-Chair: Heather Snyder, PhD

Sleep is an underexplored component of many disease processes within neuropsychiatry. In addition, it may serve as a biomarker for disease and a therapeutic target. Sleep is not measured in many clinical trials of devices, pharmaceuticals, and biomarkers. This symposium will highlight the importance of recognizing sleep state in clinical trial design. Additionally, sleep is not recognized as a potential mitigatable target for the treatment of progressive neurological disorders, where sleep disturbance can often be a prodrome in the early stages of the disease. This symposium aims to make stakeholders aware of the importance of sleep in measuring neurobehavioral outcomes and disease progression.


  • Understand the current state of knowledge regarding the mechanisms, function, and characterization of sleep, including changes across the lifespan. 
  • Identify how a genes-first approach can illuminate the bi-directional relationship between disturbed sleep and CNS disorders. 
  • Consider potential relationships among disturbed sleep, CNS disorders, and environmental factors associated with both disturbed sleep and increased risk for CNS disorders, including discussing related disparities and approaches to disentangling causal versus contributing factors.
  • Discuss research gaps and opportunities for cross-disciplinary collaboration between sleep experts and those focused on CNS disorders.


Speaker: Louis Ptáček, MD, FANA

Sleep and Neurodevelopmental Conditions

Speaker: Beth Malow, MD, MS, FANA

Sleep problems are common in conditions of neurodevelopment. In this presentation, the causes and contributors to sleep disturbances across the lifespan in autism and other conditions will be highlighted. These include attention to medical co-occurring conditions, sleep habits, and arousal dysregulation, melatonin processing, and genetic contributors. Approaches to treatment, including novel ways to disseminate findings into practice, and the use of practice pathways will be discussed. Medication options will be presented in the context of best practices.

F.E. Bennett Memorial Lectureship Award:
Glymphatic System – and Relationship to Disorder

Speaker / Award Recipient:  Maiken Nedergaard, MD, DMSc

The glymphatic system - A unidirectional fluid transport pathway that facilitates the clearance of waste products from neuronal metabolism has recently been described (Iliff, Wang et al. 2012) . Glymphatic clearance of macromolecules is driven by cerebrospinal fluid (CSF) that flows in along para-arterial spaces and through the brain parenchyma via support from astroglial aquaporin-4 water channels. The glymphatic circulation constitutes a complete anatomical pathway; para-arterial CSF exchanges with the interstitial fluid, solutes collect along para-venous spaces, then drain into the vessels of the lymphatic system for ultimate excretion from the kidney or degradation in the liver (Rasmussen, Mestre et al. 2022). The glymphatic system is mostly active during sleep and suppressed during wakefulness (Xie, Kang et al. 2013). Cardiovascular, neurological and several inflammatory diseases and aging have all been shown to inhibit glymphatic function and predispose to development of neurodegenerative diseases (Nedergaard and Goldman 2020). Chronic neuropathic and chronic stress are also negatively affecting glymphatic flow (Rasmussen, Mestre et al. 2018). These findings have led to the idea that glymphatic fluid transport acts as an integrator of general well-being and that common approaches that are known to reduce stress and improve sleep and life quality all act by improve glymphatic flow and restoring brain homeostasis.

Bidirectional relationship between sleep and Alzheimer disease-related pathology

Speaker: David Holtzman, MD, FANA

Disrupted sleep has been found to both acutely increase soluble forms of proteins critical to Alzheimer's disease pathogenesis including amyloid-beta and tau in both mouse models and humans. Chronic sleep disruption increases aggregated forms of both amyloid-beta and tau and associated neurodegeneration. Evidence suggests that acute changes in these proteins are due to both altered release and clearance. New evidence suggests that microglia play a key role in both the chronic buildup of amyloid-beta and tau. Increasing sleep has also been shown to decrease both amyloid-beta and tau pathologies. Once amyloid-beta and tau accumulate, there is evidence that these changes disrupt sleep. These findings suggest that sleep may be a novel target to influence the pathogenesis of Alzheimer disease.

Genetic Sleep Variants Protect Against Alzheimer-like Diseases

Speaker: Ying-Hui Fu, PhD

Sleep occupies a significant portion of our daily lives, yet our understanding of sleep, in general, is minimal. Sleep of sufficient duration, continuity, and intensity is necessary to promote high levels of cognitive performance during the wake period and prevent physiological changes that may predispose individuals to many adverse health outcomes. Sleep insufficiency is prevalent in our society due to the high demand for work, school, and many environmental factors, thus significantly contributing to many health conditions we face. Interestingly, the biological need for sleep varies dramatically among humans. We have identified a group of humans with unusual sleep behaviors and have used human genetics approach to identify many genes/mutations that give them unusual sleep behaviors. Mouse models recapitulate the human condition, and in vitro molecular and neurocircuitry studies offer insight into the underlying mechanisms. Because of sleep's fundamental role in our health, the pathways regulating sleep are intertwined with those regulating other functions. Thus, our method also offers opportunities to investigate how sleep can impact other conditions, including the pathology of various brain diseases.