Paper Title: Acute OSA Impacts Diurnal Alzheimer’s Biomarkers Through Nocturnal Hypoxemia and State Transitions

Journal: American Journal of Respiratory and Critical Care Medicine, June 2022

Authors: Andrew Varga, MD, Associate Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) at the Icahn School of Medicine at Mount Sinai; and other coauthors.

Bottom Line: Mount Sinai researchers have conducted one of the first studies to show the acute effect of obstructive sleep apnea on Alzheimer’s disease biomarkers, or a biological molecule in the body that signals a disease or abnormality, and the ability to even measure Alzheimer's disease biomarkers from blood.

How: Positive airway pressure (PAP) is used to treat patients with severe obstructive sleep apnea. This study uses a crossover PAP withdrawal paradigm in patients who are normally responsive to PAP at home, to evaluate overnight changes in their plasma Alzheimer’s disease biomarkers once the therapy is immediately stopped, or acute withdrawal. The researchers also evaluated whether sleep patterns including breath measures and sleep time, and measures of hypoxemic, or low levels of oxygen, fluctuate between the on and off use of PAP therapy to determine whether these conditions correlate with changes in plasma Alzheimer’s disease biomarkers.

They analyzed blood collected in the evening and next morning across a night of recorded sleep in 30 patients with severe obstructive sleep apnea during the use of therapeutic PAP or the third consecutive night without any PAP therapy.

Results: The researchers observed significant differences in the overnight change in Neurofilament Light, a marker of neural injury, and Aβ40, a peptide that serves as a building block for amyloid plaques in the brain, when they examined a patient that went from PAP therapy to immediate withdrawal of the therapeutic. Their findings suggest that obstructive sleep apnea without PAP treatment critically promotes neural injury and may foster plaque formation during overnight sleep, while use of this treatment prevents these changes. This novel evidence concludes that the burden of low oxygen levels and sleep fragmentation from obstructive sleep apnea may serve as factors contributing to overnight neural injury.

Why the Research Is Interesting: This study identifies that withdrawal of PAP therapy is linked to changes in plasma Alzheimer’s disease biomarkers, and suggests the importance of PAP therapies to restore a patient’s sleep continuity and oxygenation. The Mount Sinai team said further research is needed to determine whether the rapidly observed changes in missed PAP treatment can also predict long-term risk and progression of Alzheimer’s disease.

Said Mount Sinai's Dr. Andrew Varga of the research: Our findings add to a growing literature suggesting that untreated sleep apnea is poor for brain health and may increase risk for neurodegenerative disease. We believe this research will spark further investigations into the mechanisms by which intermittent hypoxia or sleep fragmentation injure neurons, and whether we need to consider metrics beyond the apnea-hypopnea index (AHI) in assessing brain health risk from sleep apnea—such as capturing a new measure of hypoxic burden.

Researchers from the Johns Hopkins University and New York University contributed to this study.


Journal Link: AJRCCM, June 2022