Session Schedule

Find a specific presentation in the session by navigating to the timestamp indicated below.

0:00:00
How does OSA lead to neurodegeneration? Discussion of mechanisms of oxidative stress to glymphatics.
Camilla Hoyos (Australia)

0:14:05
Can physiologic biomarkers from polysomnography predict neurodegeneration?
Najib Ayas (Canada)

0:35:05
Predicting and monitoring neurodegeneration with plasma biomarkers
Andrew Varga (United States)

0:52:08
Predicting neurocognitive response to CPAP - A step towards precision medicine?
Scott Sands (United States)
 
1:05:05
Questions and answer

Summary

Accumulating evidence implicates Obstructive sleep apnea (OSA) as a risk factor for neurodegeneration and cognitive decline, including mild cognitive impairment and Alzheimer’s disease. Mechanisms of OSA-driven neuronal injury include intermittent hypoxia, sleep fragmentation, impaired glymphatic clearance, oxidative stress and inflammation. However, there is considerable heterogeneity in the associations of OSA severity markers (e.g., apnea-hypopnea index) with neurodegeneration, making risk stratification difficult. This challenge is highlighted by a recent multidisciplinary and multinational Workshop Report (PMID: 35913462). The proposed symposium (which included co-authors of the above workshop – Ayas, Hoyos, Varga) explores emerging research on the mechanistic links, biomarkers, and therapeutic strategies for OSA-related neurodegeneration. The symposium aims to clarify the heterogeneity of neurodegeneration risk in the context of OSA, identify future research directions, and indicate potential future clinical applications.

The first talk by Dr. Hoys (Australia), How does OSA Lead to Neurodegeneration? Discussion of Mechanisms from Oxidative Stress to Glymphatics, examines the physiological and biochemical pathways by which OSA could cause neurodegeneration. In addition to systemic/cerebral inflammation and oxidative stress, this presentation will highlight the disruption of endothelial and glymphatic systems, which may influence the clearance of amyloid-beta and tau proteins. Such dysfunction accelerates brain aging and the progression of MCI to AD, providing a connection between OSA and neurodegenerative disease.

Can Polysomnographic Physiologic Biomarkers Help Predict Neurodegeneration? talk by Dr. Hajipour (senior PhD student, Canada) will discuss how novel markers could enable early detection and risk stratification for neurodegeneration in people with OSA. He will compare conventional metrics such as the AHI or duration of desaturation to the novel biomarkers derived from polysomnography, including hypoxic burden, arousal burden, EEG power spectra, and pulse rate variability in neurodegeneration. These novel metrics have shown associations with white matter hyperintensity volume, a marker of small vessel disease, cognitive decline, and incident dementia.

The third talk, Predicting and Monitoring Neurodegeneration with Plasma Biomarkers, Dr. Varga (USA) focuses on advancements in blood-based dementia markers, such as neurofilament light chain, amyloid-beta, and tau proteins. These minimally invasive tools offer promise for predicting and tracking disease progression and monitoring therapeutic responses. This talk will shed light on how integrating plasma biomarkers and sleep-dependent neurocognitive testing into clinical research designs may improve the ability of clinical trials to identify neurocognitive responses specific to OSA-related impairments.

The fourth talk, Predicting Neurocognitive Response to CPAP: A Step Towards Precision Medicine?, will explore tailoring OSA treatments to optimize cognitive outcomes. Dr. Zinchuk (USA) will summarize findings from randomized clinical trials of OSA treatment for neurocognition and present findings from secondary analyses demonstrating how physiological characteristics like arousal threshold can modify the effects of CPAP on neurocognition. Such insights may pave the way for precision medicine approaches in OSA.

Finally, an interactive Questions and Discussion Session will focus on integrating multi-modal biomarkers into research studies and clinical care. This approach could help refine patient selection, enhance therapeutic monitoring, and guide targeted interventions. By identifying those most likely to benefit, such strategies hold promise for preventing OSA-related neurocognitive decline.