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VOLUME 35, ISSUE 12

EFFECTS OF CPAP ON NEUROCOGNITIVE FUNCTION IN OSA PATIENTS: APPLES
Effects of Continuous Positive Airway Pressure on Neurocognitive Function in Obstructive Sleep Apnea Patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES)

http://dx.doi.org/10.5665/sleep.2226

Clete A. Kushida, MD, PhD1; Deborah A. Nichols, MS1; Tyson H. Holmes, PhD1; Stuart F. Quan, MD2,5; James K. Walsh, PhD3; Daniel J. Gottlieb, MD, MPH4,5; Richard D. Simon, MD6; Christian Guilleminault, MD1; David P. White, MD5; James L. Goodwin, PhD2; Paula K. Schweitzer, PhD3; Eileen B. Leary, RPSGT1; Pamela R. Hyde, MA1; Max Hirshkowitz, PhD7; Sylvan Green, MD2; Linda K. McEvoy, PhD8; Cynthia Chan, BS9; Alan Gevins, DSc9; Gary G. Kay, PhD10; Daniel A. Bloch, PhD1; Tami Crabtree, MS11; William C. Dement, MD, PhD1

1Stanford University, Stanford, CA ; 2University of Arizona, Tucson, AZ ; 3St. Luke's Hospital, Chesterfield, MO ; 4VA Boston Healthcare System, Boston, MA ; 5Brigham and Women's Hospital, Boston, MA ; 6Providence St. Mary Medical Center, Walla Walla, WA ; 7VAMC Sleep Center, Houston, TX ; 8University of California, San Diego, CA ; 9SAM Technology Inc. & The San Francisco Brain Research Institute, San Francisco, CA ; 10Georgetown University School of Medicine, Washington, DC ; 11Santa Rosa, CA



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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.

Clinical Trial Information:

Registered at clinicaltrials.gov. Identifier: NCT00051363.

Citation:

Kushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602.

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