Associations Between Sleep Quality, Sleep Architecture and Sleep Disordered Breathing and Memory After Continuous Positive Airway Pressure in Patients with Obstructive Sleep Apnea in the Apnea Positive Pressure Long-term Efficacy Study (APPLES)

Objective The role of sleep architecture in consolidation of memory has not been extensively investigated. In this study, the association of continuous positive airway pressure (CPAP) and sleep architecture and quality, and sleep disordered breathing on changes in memory are explored during the course of a 6 month clinical trial of CPAP or sham CPAP (APPLES).

Methods 848 participants had polysomnographic and memory assessments (Buschke Selective Reminding Test [Buschke] and Digit Symbol Substitution Test [DSST]) at baseline, CPAP/Sham CPAP titration, and the 2 and 6 month time points. Half were assigned to the CPAP and Sham CPAP groups respectively. Changes in performance on the Buschke and the DSST were analyzed over the course of the study between CPAP and Sham CPAP as well as in relationship to changes in sleep architecture, sleep quality and sleep disordered breathing (SDB).

Results Sleep architecture, sleep quality and SDB improved in the CPAP group at 6 months; performance on the Buschke and DSST improved equally in both CPAP and Sham CPAP groups. There also were no significant correlations between changes in the amount or percentage of sleep stages between baseline and the 6 months, and corresponding changes in either the Buschke or the DSST. However, when stratified by the upper quartile and lower 3 quartiles, greater changes in the Buschke occurred over 6 months in the top quartile of total sleep time (5.7±7.3 vs. 4.0±6.8,p≤0.01) and amount of N3 sleep (55.9±7.7 vs. 53.6±8.9 min, p≤0.01). Those with more %N3 at 6 months scored better on the Buschke as well (55.9±7.8 vs. 53.6±8.9, p≤0.01). Borderline improvement in the DSST over 6 months was observed in the top quartiles of amount of N3 and %N3. Those in the top quartile of the amount of REM and %REM also showed greater improvement in the Buschke after 6 months. No differences were observed for the AHI, but those in the top quartile of oxygen desaturation had worse scores on the Buschke at 6 months. CPAP/Sham CPAP adherence did not impact 6 month Buschke or DSST performance.

Conclusions CPAP improved long-term sleep duration, quality and architecture, but did not memory. However, large changes in REM and N3 sleep as well as moderate amounts of nocturnal hypoxemia are associated with changes in assessments of memory.

Sleep - Obstructive Sleep Apnea Syndrome - Memory - Continuous Positive Airway Pressure

Administrative Core: Clete A. Kushida, MD, PhD; Deborah A. Nichols, MS; Eileen B. Leary, BA, RPSGT; Pamela R. Hyde, MA; Tyson H. Holmes, PhD; Daniel A. Bloch, PhD; William C. Dement, MD, PhD

Data Coordinating Center: Daniel A. Bloch, PhD; Tyson H. Holmes, PhD; Deborah A. Nichols, MS; Rik Jadrnicek, Microflow, Ric Miller, Microflow Usman Aijaz, MS; Aamir Farooq, PhD; Darryl Thomander, PhD; Chia-Yu Cardell, RPSGT; Emily Kees, Michael E. Sorel, MPH; Oscar Carrillo, RPSGT; Tami Crabtree, MS; Booil Jo, PhD; Ray Balise, PhD; Tracy Kuo, PhD

Clinical Coordinating Center: Clete A. Kushida, MD, PhD, William C. Dement, MD, PhD, Pamela R. Hyde, MA, Rhonda M. Wong, BA, Pete Silva, Max Hirshkowitz, PhD, Alan Gevins, DSc, Gary Kay, PhD, Linda K. McEvoy, PhD, Cynthia S. Chan, BS, Sylvan Green, MD

Clinical Centers

Stanford University: Christian Guilleminault, MD; Eileen B. Leary, BA, RPSGT; David Claman, MD; Stephen Brooks, MD; Julianne Blythe, PA-C, RPSGT; Jennifer Blair, BA; Pam Simi, Ronelle Broussard, BA; Emily Greenberg, MPH; Bethany Franklin, MS; Amirah Khouzam, MA; Sanjana Behari Black, BS, RPSGT; Viola Arias, RPSGT; Romelyn Delos Santos, BS; Tara Tanaka, PhD

University of Arizona: Stuart F. Quan, MD; James L. Goodwin, PhD; Wei Shen, MD; Phillip Eichling, MD; Rohit Budhiraja, MD; Charles Wynstra, MBA; Cathy Ward, Colleen Dunn, BS; Terry Smith, BS; Dane Holderman, Michael Robinson, BS; Osmara Molina, BS; Aaron Ostrovsky, Jesus Wences, Sean Priefert, Julia Rogers, BS; Megan Ruiter, BS; Leslie Crosby, BS, RN

St. Mary Medical Center: Richard D. Simon Jr., MD; Kevin Hurlburt, RPSGT; Michael Bernstein, MD; Timothy Davidson, MD; Jeannine Orock-Takele, RPSGT; Shelly Rubin, MA; Phillip Smith, RPSGT; Erica Roth, RPSGT; Julie Flaa, RPSGT; Jennifer Blair, BA; Jennifer Schwartz, BA; Anna Simon, BA; Amber Randall, BA

St. Luke's Hospital: James K. Walsh, PhD, Paula K. Schweitzer, PhD, Anup Katyal, MD, Rhody Eisenstein, MD, Stephen Feren, MD, Nancy Cline, Dena Robertson, RN, Sheri Compton, RN, Susan Greene, Kara Griffin, MS, Janine Hall, PhD

Brigham and Women's Hospital: Daniel J. Gottlieb, MD, MPH, David P. White, MD, Denise Clarke, BSc, RPSGT, Kevin Moore, BA, Grace Brown, BA, Paige Hardy, MS, Kerry Eudy, PhD, Lawrence Epstein, MD, Sanjay Patel, MD

Sleep HealthCenters for the use of their clinical facilities to conduct this research

Consultant Teams

Methodology Team: Daniel A. Bloch, PhD, Sylvan Green, MD, Tyson H. Holmes, PhD, Maurice M. Ohayon, MD, DSc, David White, MD, Terry Young, PhD

Sleep-Disordered Breathing Protocol Team: Christian Guilleminault, MD, Stuart Quan, MD, David White, MD

EEG/Neurocognitive Function Team: Jed Black, MD, Alan Gevins, DSc, Max Hirshkowitz, PhD, Gary Kay, PhD, Tracy Kuo, PhD

Mood and Sleepiness Assessment Team: Ruth Benca, MD, PhD, William C. Dement, MD, PhD, Karl Doghramji, MD, Tracy Kuo, PhD, James K. Walsh, PhD

Quality of Life Assessment Team: W. Ward Flemons, MD, Robert M. Kaplan, PhD

APPLES Secondary Analysis-Neurocognitive (ASA-NC) Team: Dean Beebe, PhD, Robert Heaton, PhD, Joel Kramer, PsyD, Ronald Lazar, PhD, David Loewenstein, PhD, Frederick Schmitt, PhD

National Heart, Lung, and Blood Institute (NHLBI)

Michael J. Twery, PhD, Gail G. Weinmann, MD, Colin O. Wu, PhD

Data and Safety Monitoring Board (DSMB)

Seven-year term: Richard J. Martin, MD (Chair), David F. Dinges, PhD, Charles F. Emery, PhD, Susan M. Harding MD, John M. Lachin, ScD, Phyllis C. Zee, MD, PhD

Other term: Xihong Lin, PhD (2 y), Thomas H. Murray, PhD (1 y).

Publication History

Received: 12 June 2018

Accepted: 27 September 2018

Article published online:
16 October 2023

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