Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: The apnea positive pressure long-term efficacy study (APPLES)

Clete A. Kushida, Deborah A. Nichols, Tyson H. Holmes, Stuart F. Quan, James K. Walsh, Daniel J. Gottlieb, Richard D. Simon, Christian Guilleminault, David P. White, James L. Goodwin, Paula K. Schweitzer, Eileen B. Leary, Pamela R. Hyde, Max Hirshkowitz, Sylvan Green, Linda K. McEvoy, Cynthia Chan, Alan Gevins, Gary G. Kay, Daniel A. BlochTami Crabtree, William C. Dement

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172 Scopus citations


Study Objective: To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA). Design, Setting, and Participants: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures. Intervention: Active or sham CPAP Measurements: Three neurocognitive variables, each representing a neurocognitive domain: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F]) Results: The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test. Conclusions: CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship.

Original languageEnglish (US)
Pages (from-to)1593-1602
Number of pages10
Issue number12
StatePublished - Dec 1 2012



  • Continuous positive airway pressure
  • Neurocognitive function
  • Obstructive sleep apnea
  • Randomized controlled trial
  • Sleepiness

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology (medical)

Cite this

Kushida, C. A., Nichols, D. A., Holmes, T. H., Quan, S. F., Walsh, J. K., Gottlieb, D. J., Simon, R. D., Guilleminault, C., White, D. P., Goodwin, J. L., Schweitzer, P. K., Leary, E. B., Hyde, P. R., Hirshkowitz, M., Green, S., McEvoy, L. K., Chan, C., Gevins, A., Kay, G. G., ... Dement, W. C. (2012). Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: The apnea positive pressure long-term efficacy study (APPLES). Sleep, 35(12), 1593-1602. https://doi.org/10.5665/sleep.2226