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)
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
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.
Active or sham CPAP
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])
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.
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.
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.