NEUROCOGNITIVE AND PSYCHOSOCIAL OUTCOMES IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA TREATED WITH CONTINUOUS POSITIVE AIRWAY PRESSURE by Esther Yuet Ying Lau Submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Dalhousie University Halifax, Nova Scotia June 2008 © Copyright by Esther Yuet Ying Lau, 2008 Library and Bibliotheque et 1*1 Archives Canada Archives Canada Published Heritage Direction du Branch Patrimoine de I'edition 395 Wellington Street 395, rue Wellington Ottawa ON K1A0N4 Ottawa ON K1A0N4 Canada Canada Your file Votre reference ISBN: 978-0-494-43943-2 Our file Notre reference ISBN: 978-0-494-43943-2 NOTICE: AVIS: The author has granted a non­ L'auteur a accorde une licence non exclusive exclusive license allowing Library permettant a la Bibliotheque et Archives and Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par telecommunication ou par I'lnternet, prefer, telecommunication or on the Internet, distribuer et vendre des theses partout dans loan, distribute and sell theses le monde, a des fins commerciales ou autres, worldwide, for commercial or non­ sur support microforme, papier, electronique commercial purposes, in microform, et/ou autres formats. paper, electronic and/or any other formats. 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TABLE OF CONTENTS LIST OF TABLES viii LIST OF FIGURES x ABSTRACT xi LIST OF ABBREVIATIONS AND SYMBOLS USED xii ACKNOWLEDGEMENTS xiv CHAPTER ONE: INTRODUCTION 1 OVERVIEW OF OSA 1 Definitions and Prevalence 1 Pathophysiology of OSA 3 Sleep Architecture Associated with OSA 5 Treatments for OSA 5 MEDICAL SEQUELAE OF OSA 6 DAYTIME CONSEQUENCES OF OSA 8 Excessive Daytime Sleepiness and Daily Functioning 8 Mood 12 Quality of Life 17 OSA AND NEUROCOGNITIVE CONSEQUENCES 21 Global Intellectual Functioning 22 Attention and Concentration 23 Motor Functions 24 Memory 26 Executive Function 27 MECHANISMS OF THE NEUROCOGNITIVE DYSFUNCTION 33 NEUROIMAGING FINDINGS ON PATIENTS WITH OSA 43 Prefrontal Cortex (PFC) and Sleep 50 REVERSIBILITY OF DAYTIME DYSFUNCTIONS WITH TREATMENT OF CPAP 52 THEORY OF WORKING MEMORY 61 PURPOSE OF THE PRESENT STUDY 65 CHAPTER TWO: METHODS 68 PARTICIPANTS AND DESIGN 68 OSA Group 68 Controls 69 Design 70 Procedures 71 v MEASURES AND TESTS 72 Screening 72 Hospital Record 74 Clinical and Demographic Variables 74 Sleep Questionnaires (Appendix D) 74 Mood Assessment 76 Functional Outcomes and Quality of Life 77 Polysomnography 79 Neuropsychological Variables 80 Working Memory Components 81 STATISTICAL ANALYSES 92 CHAPTER THREE: RESULTS 95 PARTICIPANTS' CHARACTERISTICS 95 PRE- AND POST-TREATMENT COMPARISONS 95 BETWEEN-GROUP COMPARISONS 97 Polysomnography 97 Working Memory Tasks 97 Neuropsychological Tests 103 Sleep Questionnaires 105 Mood Assessment 105 Daily Functioning and Quality of Life 106 REGRESSION ANALYSES 106 Working Memory Tasks 106 Neuropsychological Tests 107 Mood, Daily Functioning, and Quality of Life 108 CORRELATIONAL ANALYSES 109 CHAPTER FOUR: DISCUSSION 111 EFFECTIVENESS OF CPAP TREATMENT 111 PERFORMANCE OF INDIVIDUALS WITH OSA TREATED WITH CPAP ON NEUROCOGNITIVE MEASURES 116 Basic Storage and Rehearsal Components of Working Memory 117 Central Executive Function of Working Memory 117 Neuropsychological Tests 123 PREDICTORS OF RESIDUAL NEUROCOGNITIVE DEFICITS 127 VI PREDICTORS OF PSYCHOSOCIAL OUTCOMES 130 Emotional Functioning 131 Daily Functioning 132 Quality of Life 133 IMPACT OF EXECUTIVE DIFFICULTIES ON PERCEIVED COGNITIVE EFFICIENCY AND QUALITY OF LIFE 134 FACTORS RELATING TO QUALITY OF LIFE 135 OTHER FINDINGS OF INTERESTS 137 Between-Group Comparison on Sleep Related Variables After Treatment 137 Between-Group Comparison on Emotional Functioning After Treatment 138 Between-Group Comparison on Daily Functioning and Quality of Life 138 Undetected OSA in Community Dwelling Individuals 139 STRENGTHS AND LIMITATIONS OF THE CURRENT STUDY 140 FUTURE RESEARCH DIRECTIONS 144 CHAPTER FIVE: CONCLUSIONS 147 REFERENCES 200 APPENDIX A - SCREENING QUESTIONNAIRES 229 APPENDIX B - MEDICAL RECORD SUMMARY & PRE-TREATMENT SLEEP STUDY FORM 246 APPENDIX C - HEALTH INTERVIEW 248 APPENDIX D - SLEEP AND PSYCHOSOCIAL QUESTIONNAIRES 250 APPENDIX E - NEUROPSYCHOLOGICAL TESTS 267 APPENDIX F - WORKING MEMORY SPAN 277 vn LIST OF TABLES Table 1 Group Demographic Characteristics 150 Table 2 OSA Group Medical History 150 Table 3 Pre- and Post-treatment Comparisons on Respiratory and Hypoxemia Indices, Sleep Questionnaires, Daytime Function, and Quality of Life 151 Table 4 Comparison between the OSA Group Treated with CPAP and the Control Group on Polysomnographic Variables 152 Table 5 Comparison between the OSA Group Treated with CPAP and the Control Group on Verbal Working Memory Tasks 153 Table 6 Comparison between the OSA Group Treated with CPAP and the Control Group on Spatial Working Memory Tasks 154 Table 7 Comparison between the OSA Group Treated with CPAP and the Control Group on the Verbal-Spatial Dual Task 155 Table 8 Comparison between the OSA Group Treated with CPAP and the Control Group on the Working Memory Span Task 155 Table 9 Comparison between the OSA Group Treated with CPAP and the Control Group on Standardized Neuropsychological Tests (Raw Scores) 156 Table 10 Number of Participants and Within-group Percentages of the OSA Group Treated with CPAP and the Control Group with Scores Below Clinical Cut-offs Defined by Norms on Standardized Neuropsychological Tests 158 Table 11 Comparison between the OSA Group Treated with CPAP and the Control Group on Sleep Questionnaires 160 Table 12 Comparison between the OSA Group Treated with CPAP and the Control Group on Mood Questionnaires 161 Table 13 Comparison between the OSA Group Treated with CPAP and the Control Group on Functional Outcome Measures 162 Table 14 Comparison between the OSA Group Treated with CPAP and the Control Group on Quality of Life Measures 163 Table 15a Significant Predictors of Neurocognitive Outcomes Based on Stepwise Regressions in Participants with OSA Treated with CPAP 164 Vlll Table 15b Stepwise Regression Model of the Verbal 2-back Task in Participants with OSA Treated with CPAP 165 Table 15c Stepwise Regression Model of the Spatial 2-back Task in Participants with OSA Treated with CPAP 166 Table 15d Stepwise Regression Model of the Working Memory Span - Sentence Verification Proportion in Participants with OSA Treated with CPAP 167 Table 15e Stepwise Regression Model of Digit Symbol in Participants with OSA Treated with CPAP 168 Table 15f Stepwise Regression Model of Wisconsin Card Sorting Test in Participants with OSA Treated with CPAP 169 Table 15g Stepwise Regression Model of Grooved Pegboard Test in Participants with OSA Treated with CPAP 170 Table 16a Significant Predictors of Psychosocial Outcomes Based on Stepwise Regressions in Participants with OSA Treated with CPAP 171 Table 16b Stepwise Regression Model of the Beck Depression Inventory in Participants with OSA Treated with CPAP 172 Table 16c Stepwise Regression Model of the Profile of Mood States in Participants with OSA Treated with CPAP 173 Table 16d Stepwise Regression Model of the Functional Outcomes of Sleep Questionnaire in Participants with OSA Treated with CPAP 177 Table 16e Stepwise Regression Model of the Cognitive Failures Questionnaire in Participants with OSA Treated with CPAP 180 Table 16f Stepwise Regression Model of the Quebec Sleep Questionnaire in Participants with OSA Treated with CPAP 181 Table 16g Stepwise Regression Model of the Quality of Life - Visual Analogue Scale in Participants with OSA Treated with CPAP 184 Table 17 Correlations of Quebec Sleep Questionnaire with Functional Outcomes of Sleep Questionnaire, Beck Depression Inventory, and Profile of Mood States 185 IX LIST OF FIGURES Figure 1 Prefrontal Model of OSA Deficits 186 Figure 2 Working Memory Model 187 Figure 3 Sequence of Events in the Verbal Memory Scanning Task 188 Figure 4 Sequence of Events in the Spatial Memory Scanning Task 189 Figure 5 Schematic of the Tracking Component of the Verbal-Spatial Dual Task 190 Figure 6 Sequence of Events in the Verbal 2-Back Task 191 Figure 7 Sequence of Events