CPAP and cognition in OSA (APPLES)

David J. Berlowitz, Shirin Shafazand

Research output: Contribution to journalComment/debatepeer-review

5 Scopus citations


Question: What is the effect of continuous positive airway pressure (CPAP) therapy versus Sham CPAP therapy on neurocognitive function in patients with obstructive sleep apnea (OSA)? Design: Multi-center, randomized, double blinded, sham controlled trial; Identifier: NCT00051363. Allocation: The Data Coordinating Center used a computerized permuted block design to randomize participants to the 2 study arms. Blinding: Participants and most personnel were blinded to treatment assignments, with the exception of site coordinators, polysomnography (PSG) technologists, and the database administrator/data manager. Follow-up period: 6 month follow-up; the first participant was enrolled in 11/2003 and the final completion month was 8/2008. Setting: 5 clinical sleep centers in the United States (academic and private settings). Subjects: 1,098 participants (556 active CPAP, 542 sham CPAP, 35% women, mean age 52 years in active CPAP group) who were diagnosed with OSA with apnea hypopnea index (AHI) ≥ 10 events per hour were randomized. The primary exclusion criteria were: 1) prior OSA treatment with CPAP or surgery; 2) anyone in the household with current/past CPAP use; 3) sleepiness-related automobile accident within past year; 4) oxygen saturation < 75% for > 10% of the diagnostic PSG total sleep time; and/or 5) conditions (including known neurocognitive impairment), disorders, medications, or substances that could potentially affect neurocognitive function and/or alertness. Subjects were recruited primarily from patients scheduled in a regular sleep clinic for evaluation of possible OSA and from local advertising. Although recruitment source was not tracked, it was estimated that initial contact with ∼70% of the subjects occurred as a result of advertisement. Intervention: Participants were randomized to receive CPAP treatment or sham CPAP. Outcomes: The primary outcomes were 3 neurocognitive variables, each representing a neurocognitive domain: 1) Pathfinder Number Test-Total Time assesses attention and psychomotor function; 2) Buschke Selective Reminding Test-Sum Recall assesses verbal learning and memory; and 3) Sustained Working Memory Test-Overall Mid-Day Index assesses an executive and frontal-lobe function (E/F). The secondary outcomes were 7 neurocognitive and 2 sleepiness measures (the maintenance of wakefulness test and the Epworth Sleepiness Scale). The sample size was based on pilot study results for the Pathfinder Number Test. A target of 1,100 total participants (assuming 90% power, 2-sided α = 0.05, 20% study dropout, and allowing for 3 interim analyses) was estimated to achieve an effect size of 0.2, translating to the clinically significant difference of 26 msec in reaction time between the Active and Sham CPAP groups. An effect size of ≥ 0.2 is also a clinically significant between group difference for the other two primary outcome measures. Patient Follow-Up: intention to treat analysis, 79% completed follow-up in active arm, 74% in sham arm. Main Results: There was no statistically significant difference between the groups in the primary outcomes at 6 months. 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 that did not persist at 6 months. When primary neurocognitive analyses were restricted to CPAP-adherent individuals (mean nightly active or sham CPAP adherence ≥ 4 h for the 2 months prior to each neurocognitive testing visit), no differences in means were detected between arms for any of the primary outcomes at any visit. 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. Conclusion: In adults with OSA, CPAP therapy did not improve neurocognitive measures at 6 months compared with those on sham CPAP therapy.

Original languageEnglish (US)
Pages (from-to)515-516
Number of pages2
JournalJournal of Clinical Sleep Medicine
Issue number5
StatePublished - May 15 2013

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Neurology
  • Clinical Neurology


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