Continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea is most effective in improving neurocognition in people who have a high arousal threshold, according to a new research analysis. The study, published in the European Respiratory Journal, suggests that CPAP, currently used as a one-size-fits-all treatment, may not be beneficial for all people with obstructive sleep apnea.
Obstructive sleep apnea is a common chronic condition in which the soft tissues in the back of the throat relax and block the airway during sleep. This leads to pauses in breathing, resulting in low oxygen levels and repeated awakenings throughout the night. Obstructive sleep apnea is associated with cognitive decline, particularly with impairments in executive function—a set of skills that includes the capacity to plan, display self-control, and follow directions.
While CPAP is the go-to treatment for all patients with obstructive sleep apnea, randomized clinical trials have yet to find that it can improve neurocognition.
“When we see patients in clinic, we find that cognition improves with CPAP in some people, but not in others,” said Andrey Zinchuk, MD, MHS, assistant professor and director of the Advanced Apnea Management Program in the Section of Pulmonary, Critical Care and Sleep Medicine at Yale School of Medicine.
Part of the reason why this is important is because sleep apnea is so prevalent, affecting as many as one billion people worldwide.
Zinchuk and his collaborators from Harvard, Mount Sinai, Stanford, and SUNY Upstate wanted to understand why. “So, we went back and re-analyzed data from the Apnea Positive Pressure Long-term Efficacy Study (APPLES), the largest clinical trial of CPAP for neurocognition. This study showed no effect of CPAP in all-comers.”
The investigators measured a recently discovered physiological feature of obstructive sleep apnea, the arousal threshold, from sleep studies of APPLES participants. People with obstructive sleep apnea who have a low arousal threshold wake up easily from minor disturbances in breathing or oxygen levels; those with a high arousal threshold only wake up in response to worse airway collapse or deeper drops in oxygen levels.
“Instead of looking at whether people simply got CPAP or not, we looked to see if CPAP had different effects in those with low versus high arousal threshold,” said Zinchuk. “What we found was that if you have a high arousal threshold, you are going to benefit from CPAP therapy in terms of executive function. The effect is like drinking a cup of coffee. But you're unlikely to benefit if you have a low arousal threshold.”
Typically, people with a low arousal threshold also have a harder time sticking with CPAP treatment.
Current clinical guidelines recommend CPAP therapy across the board without taking arousal threshold into account. “This study shows that we can now begin to identify which patients are most likely to benefit from CPAP based on their physiological characteristics,” Zinchuk said.
Klar Yaggi, MD, MPH, professor of medicine and director of the Yale New Haven Health Sleep Centers and the Program in Clinical and Translational Sleep and Lung Neurobiology Research in the Section of Pulmonary, Critical Care and Sleep Medicine, noted that the study is an excellent example of applying precision medicine approaches to better understand which patients are most likely to derive specific benefits from CPAP therapy.
“By identifying physiological traits like arousal threshold, we are moving towards more tailored and effective treatments for obstructive sleep apnea,” Yaggi said.
Future research will focus on the mechanisms of why arousal threshold matters in response to CPAP and prospectively examine CPAP adherence and cardiovascular and neurocognitive health. Findings could help clinicians and patients make more informed decisions and prioritize CPAP for those most likely to benefit.
“Part of the reason why this is important is because sleep apnea is so prevalent, affecting as many as one billion people worldwide,” Zinchuk said. “There's no way that you can treat everybody with sleep apnea, and you probably shouldn't be treating everybody with CPAP. It’s very exciting because now we have a way of classifying people into who might and who might not benefit from treatment. This knowledge may help us find the right treatment for the right patient.”
Other authors of the study include Clete A. Kushida, MD, PhD, from Stanford University; Alexander Walker, MD, from SUNY Upstate Medical University; Andrew Wellman, MD, PhD, Ali Azarbarzin, PhD, Raichel M. Alex, PhD, and Scott A. Sands, PhD, from Harvard Medical School; and Andrew W. Varga, MD, from Mount Sinai Integrative Sleep Center.
The Section of Pulmonary, Critical Care and Sleep Medicine is one of the 11 sections within Yale School of Medicine’s Department of Internal Medicine. To learn more about Yale-PCCSM, visit PCCSM's website, or follow us on Facebook and Twitter.