The Apnea Positive Pressure Long-term Efficacy Study (APPLES): rationale, design, methods, and procedures.

STUDY OBJECTIVE To assess the size, time course, and durability of the effects of long-term continuous positive airway pressure (CPAP) therapy on neurocognitive function, mood, sleepiness, and quality of life in patients with obstructive sleep apnea. DESIGN Randomized, double-blinded, 2-arm, sham-controlled, multicenter, long-term, intention-to-treat trial of CPAP therapy. SETTING Sleep clinics and laboratories at 5 university medical centers and community-based hospitals. PATIENTS OR PARTICIPANTS Target enrollment is 1100 randomly assigned subjects across 5 clinical centers. INTERVENTIONS Active versus sham (subtherapeutic) CPAP. MEASUREMENTS AND RESULTS A battery of conventional and novel tests designed to evaluate neurocognitive function, mood, sleepiness, and quality of life. CONCLUSIONS The Apnea Positive Pressure Long-term Efficacy Study (APPLES) is designed to study obstructive sleep apnea and test the effects of CPAP through a comprehensive, controlled, and long-term trial in a large sample of subjects with obstructive sleep apnea.

[1]  Murray Johns,et al.  The Epworth Sleepiness Scale , 2007 .

[2]  L. McEvoy,et al.  Characterizing impaired functional alertness from diphenhydramine in the elderly with performance and neurophysiologic measures. , 2006, Sleep.

[3]  Alan Gevins,et al.  Effects of marijuana on neurophysiological signals of working and episodic memory , 2004, Psychopharmacology.

[4]  L. McEvoy,et al.  The impact of moderate sleep loss on neurophysiologic signals during working-memory task performance. , 2002, Sleep.

[5]  Alan Gevins,et al.  Task-related EEG and ERP changes without performance impairment following a single dose of phenytoin , 2002, Clinical Neurophysiology.

[6]  J. R. Hays,et al.  Concurrent Validity of the Wechsler Abbreviated Scale of Intelligence and the Kaufman Brief Intelligence Test among Psychiatric Inpatients , 2002, Psychological reports.

[7]  B. Axelrod.  Validity of the Wechsler Abbreviated Scale of Intelligence and Other Very Short Forms of Estimating Intellectual Functioning , 2002, Assessment.

[8]  Alan Gevins,et al.  Tracking the Cognitive Pharmacodynamics of Psychoactive Substances with Combinations of Behavioral and Neurophysiological Measures , 2002, Neuropsychopharmacology.

[9]  N. Douglas,et al.  Treatment with Continuous Positive Airway Pressure Is Not Effective in Patients with Sleep Apnea but No Daytime Sleepiness , 2001, Annals of Internal Medicine.

[10]  R. Coppola,et al.  Specific versus Nonspecific Brain Activity in a Parametric N-Back Task , 2000, NeuroImage.

[11]  A. Gevins,et al.  Neurophysiological measures of working memory and individual differences in cognitive ability and cognitive style. , 2000, Cerebral cortex.

[12]  N J Douglas,et al.  Cognitive function in the sleep apnea/hypopnea syndrome (SAHS). , 2000, Sleep.

[13]  J. Montplaisir,et al.  Cognitive deficits associated with sleep apnea syndrome: a proposed neuropsychological test battery. , 2000, Sleep.

[14]  Bonnie K. Lind,et al.  Association of Sleep-Disordered Breathing, Sleep Apnea, and Hypertension in a Large Community-Based Study , 2000 .

[15]  A. Agustí,et al.  Long-term effects of CPAP on daytime functioning in patients with sleep apnoea syndrome. , 2000, The European respiratory journal.

[16]  M. Johns,et al.  Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the Epworth sleepiness scale: Failure of the MSLT as a gold standard , 2000, Journal of sleep research.

[17]  J. Stradling,et al.  Randomised prospective parallel trial of therapeutic versus subtherapeutic nasal continuous positive airway pressure on simulated steering performance in patients with obstructive sleep apnoea , 2000, Thorax.

[18]  I. Deary,et al.  Predictors of improvements in daytime function outcomes with CPAP therapy. , 2000, American journal of respiratory and critical care medicine.

[19]  A Gevins,et al.  Test–retest reliability of cognitive EEG , 2000, Clinical Neurophysiology.

[20]  T. Akashiba,et al.  Long-term effects nasal continuous positive airway pressure on daytime sleepiness, mood and traffic accidents in patients with obstructive sleep apnoea. , 2000, Respiratory medicine.

[21]  C. Dowrick,et al.  The use of the Beck Depression Inventory to screen for depression in the general population: a preliminary analysis. , 2000, Journal of affective disorders.

[22]  S. Ancoli-Israel,et al.  Effect of continuous positive airway pressure vs placebo continuous positive airway pressure on sleep quality in obstructive sleep apnea. , 1999, Chest.

[23]  Cross-validation of the two- and three-subtest short forms of the Wechsler Memory Scale-Revised. , 1999, Applied neuropsychology.

[24]  A. Gevins,et al.  Detecting transient cognitive impairment with EEG pattern recognition methods. , 1999, Aviation, space, and environmental medicine.

[25]  S. Ancoli-Israel,et al.  Effect of CPAP treatment on mood states in patients with sleep apnea. , 1999, Journal of psychiatric research.

[26]  Daniel J Buysse,et al.  Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. , 1999, Sleep.

[27]  A Gevins,et al.  Electroencephalographic imaging of higher brain function. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[28]  Crispin Jenkinson,et al.  Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial , 1999, The Lancet.

[29]  D. Navajas,et al.  Sham continuous positive airway pressure for placebo-controlled studies in sleep apnoea , 1999, The Lancet.

[30]  N. Douglas,et al.  Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome. , 1999, American journal of respiratory and critical care medicine.

[31]  M. Partinen,et al.  Cognitive function and treatment of obstructive sleep apnea syndrome , 1999, Journal of sleep research.

[32]  D. Chadwick,et al.  Placebo-controlled studies in neurology , 1999, Neurology.

[33]  R. Rodríguez-Roisín,et al.  Evidence of the effectiveness of continuous positive airway pressure in the treatment of sleep apnea/hypopnea syndrome. , 1999, American journal of respiratory and critical care medicine.

[34]  I. Deary,et al.  Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep Apnea/Hypopnea syndrome. , 1999, American journal of respiratory and critical care medicine.

[35]  D. Nyenhuis,et al.  Adult and geriatric normative data and validation of the profile of mood states. , 1999, Journal of clinical psychology.

[36]  W. Gouvier,et al.  External validation of the equivalence of two computational formulas for a WAIS-R seven-subtest short form. , 1999, Applied neuropsychology.

[37]  L. McEvoy,et al.  Neurophysiological indices of strategy development and skill acquisition. , 1999, Brain research. Cognitive brain research.

[38]  N J Douglas,et al.  Does arousal frequency predict daytime function? , 1998, The European respiratory journal.

[39]  R M Kaplan,et al.  The Quality of Well-Being Scale: critical similarities and differences with SF-36. , 1998, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[40]  A Gevins,et al.  Dynamic cortical networks of verbal and spatial working memory: effects of memory load and task practice. , 1998, Cerebral cortex.

[41]  R. Kaplan,et al.  Performance of a self-administered mailed version of the Quality of Well-Being (QWB-SA) questionnaire among older adults. , 1998, Medical care.

[42]  W. Flemons,et al.  Development of a disease-specific health-related quality of life questionnaire for sleep apnea. , 1998, American journal of respiratory and critical care medicine.

[43]  J. Malin,et al.  Neuropsychological investigations and event-related potentials in obstructive sleep apnea syndrome before and during CPAP-therapy , 1998, Journal of the Neurological Sciences.

[44]  C. Feuerstein,et al.  Cognitive executive dysfunction in patients with obstructive sleep apnea syndrome (OSAS) after CPAP treatment. , 1998, Sleep.

[45]  A. Gevins.  The future of electroencephalography in assessing neurocognitive functioning. , 1998, Electroencephalography and clinical neurophysiology.

[46]  T. Hergueta,et al.  The mini international neuropsychiatric interview , 1998, European Psychiatry.

[47]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[48]  J. Samet,et al.  The Sleep Heart Health Study: design, rationale, and methods. , 1997, Sleep.

[49]  M M Mitler,et al.  A normative study of the maintenance of wakefulness test (MWT). , 1997, Electroencephalography and clinical neurophysiology.

[50]  J. Stradling,et al.  Comparison of three measures of quality of life outcome in the evaluation of continuous positive airways pressure therapy for sleep apnoea , 1997, Journal of sleep research.

[51]  I. Fietze,et al.  Arousals and sleep stages in patients with obstructive sleep apnoea syndrome: changes under nCPAP treatment , 1997, Journal of sleep research.

[52]  J. Pépin,et al.  Frontal lobe-related cognitive functions in patients with sleep apnea syndrome before and after treatment. , 1997, Acta Neurologica Belgica.

[53]  Daphne N. Yu,et al.  High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice. , 1997, Cerebral cortex.

[54]  R. Chervin,et al.  Compliance with nasal CPAP can be improved by simple interventions. , 1997, Sleep.

[55]  T. Sheldon,et al.  Health effects of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure: a systematic review of the research evidence , 1997, BMJ.

[56]  J. Walsworth-Bell.  Sleep apnoea and the misuse of evidence-based medicine , 1997, The Lancet.

[57]  W. Flemons,et al.  Quality of life consequences of sleep-disordered breathing. , 1997, The Journal of allergy and clinical immunology.

[58]  J. Stradling.  Sleep apnoea and the misuse of evidence-based medicine , 1997, The Lancet.

[59]  Edward E. Smith,et al.  A Parametric Study of Prefrontal Cortex Involvement in Human Working Memory , 1996, NeuroImage.

[60]  W. Flemons,et al.  The diagnosis of sleep apnea: questionnaires and home studies. , 1996, Sleep.

[61]  E. Sforza,et al.  Long-term compliance with CPAP therapy in obstructive sleep apnea patients and in snorers. , 1996, Sleep.

[62]  J Zieliński,et al.  Effects of CPAP treatment on psychological status in patients with severe obstructive sleep apnoea , 1996, Journal of sleep research.

[63]  C. Guilleminault,et al.  Cognitive function in patients with sleep apnea after acute nocturnal nasal continuous positive airway pressure (CPAP) treatment: sleepiness and hypoxemia effects. , 1996, Journal of clinical and experimental neuropsychology.

[64]  L. McEvoy,et al.  High resolution evoked potential imaging of the cortical dynamics of human working memory. , 1996, Electroencephalography and clinical neurophysiology.

[65]  N J Douglas,et al.  The effect of sleep fragmentation on daytime function. , 1996, American journal of respiratory and critical care medicine.

[66]  J. Greene.  Contributions to Neuropsychological Assessment , 1995 .

[67]  J. Pépin,et al.  Deficits of cognitive executive functions in patients with sleep apnea syndrome. , 1995, Sleep.

[68]  R. Kaplan.  Value Judgment in the Oregon Medicaid Experiment , 1994, Medical care.

[69]  I. Deary,et al.  Effect of continuous positive airway pressure treatment on daytime function in sleep apnoea/hypopnoea syndrome , 1994, The Lancet.

[70]  R. Kaplan.  An outcomes-based model for directing decisions in women's health care. , 1994, Clinical obstetrics and gynecology.

[71]  D. Dinges,et al.  Vigilance decrement and sleepiness. , 1994 .

[72]  A. Gevins,et al.  Spatiotemporal dynamics of component processes in human working memory. , 1993, Electroencephalography and clinical neurophysiology.

[73]  A. Pack,et al.  Effects of one night without nasal CPAP treatment on sleep and sleepiness in patients with obstructive sleep apnea. , 1993, The American review of respiratory disease.

[74]  F. Richer,et al.  Persistent neuropsychological deficits and vigilance impairment in sleep apnea syndrome after treatment with continuous positive airways pressure (CPAP). , 1993, Journal of clinical and experimental neuropsychology.

[75]  R. Reitan,et al.  The Halstead-Reitan neuropsychological test battery: Theory and clinical interpretation , 1993 .

[76]  M. Johns.  Daytime sleepiness, snoring, and obstructive sleep apnea. The Epworth Sleepiness Scale. , 1993, Chest.

[77]  F. Richer,et al.  Neurobehavioral manifestations in obstructive sleep apnea syndrome before and after treatment with continuous positive airway pressure. , 1992, Sleep.

[78]  M. Johns,et al.  Reliability and factor analysis of the Epworth Sleepiness Scale. , 1992, Sleep.

[79]  E. Sforza,et al.  Daytime sleepiness after long-term continuous positive airway pressure (CPAP) treatment in obstructive sleep apnea syndrome , 1992, Journal of the Neurological Sciences.

[80]  J. Conway,et al.  Treatment of obstructive sleep apnea with nasal continuous positive airway pressure. Patient compliance, perception of benefits, and side effects. , 1992, The American review of respiratory disease.

[81]  N J Douglas,et al.  Factors impairing daytime performance in patients with sleep apnea/hypopnea syndrome. , 1992, Archives of internal medicine.

[82]  F. Richer,et al.  Obstructive sleep apnea syndrome: pathogenesis of neuropsychological deficits. , 1991, Journal of clinical and experimental neuropsychology.

[83]  M. Johns,et al.  A new method for measuring daytime sleepiness: the Epworth sleepiness scale. , 1991, Sleep.

[84]  A S Gevins,et al.  Effects of prolonged mental work on functional brain topography. , 1990, Electroencephalography and clinical neurophysiology.

[85]  S. Derderian,et al.  Neuropsychologic symptoms in obstructive sleep apnea improve after treatment with nasal continuous positive airway pressure. , 1988, Chest.

[86]  L. Findley,et al.  Automobile accidents involving patients with obstructive sleep apnea. , 1988, The American review of respiratory disease.

[87]  D. Deptula,et al.  Neuropsychological dysfunction in sleep apnea. , 1987, Sleep.

[88]  L J Findley,et al.  Cognitive impairment in patients with obstructive sleep apnea and associated hypoxemia. , 1986, Chest.

[89]  H. Julia Hannay,et al.  Experimental techniques in human neuropsychology , 1986 .

[90]  David F. Dinges,et al.  Microcomputer analyses of performance on a portable, simple visual RT task during sustained operations , 1985 .

[91]  H. Levin,et al.  Selective reminding test: an examination of the equivalence of four forms. , 1985, Journal of clinical and experimental neuropsychology.

[92]  J. Yesavage,et al.  Preliminary communication: intellectual deficit and sleep-related respiratory disturbance in the elderly. , 1985, Sleep.

[93]  K. K. Lan,et al.  Discrete sequential boundaries for clinical trials , 1983 .

[94]  I. Grant,et al.  Neuropsychologic findings in hypoxemic chronic obstructive pulmonary disease. , 1982, Archives of internal medicine.

[95]  M. Mitler,et al.  Maintenance of wakefulness test: a polysomnographic technique for evaluation treatment efficacy in patients with excessive somnolence. , 1982, Electroencephalography and clinical neurophysiology.

[96]  C. Golden,et al.  Neuropsychological deficits among patients with chronic obstructive pulmonary disease. , 1982, The International journal of neuroscience.

[97]  R Broughton,et al.  Sensitivity of the stanford sleepiness scale to the effects of cumulative partial sleep deprivation and recovery oversleeping. , 1981, Sleep.

[98]  ColinE. Sullivan,et al.  REVERSAL OF OBSTRUCTIVE SLEEP APNOEA BY CONTINUOUS POSITIVE AIRWAY PRESSURE APPLIED THROUGH THE NARES , 1981, The Lancet.

[99]  P. O'Brien,et al.  A multiple testing procedure for clinical trials. , 1979, Biometrics.

[100]  S. Pocock.  Randomised clinical trials. , 1977, British medical journal.

[101]  D. Gronwall.  Paced Auditory Serial-Addition Task: A Measure of Recovery from Concussion , 1977, Perceptual and motor skills.

[102]  J. Horne,et al.  A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. , 1976, International journal of chronobiology.

[103]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[104]  HERMAN BUSCHKE,et al.  Evaluating storage, retention, and retrieval in disordered memory and learning , 1974, Neurology.

[105]  Herman Buschke,et al.  Selective reminding for analysis of memory and learning , 1973 .

[106]  W. Dement,et al.  Quantification of sleepiness: a new approach. , 1973, Psychophysiology.

[107]  A. Rechtschaffen,et al.  A manual of standardized terminology, technique and scoring system for sleep stages of human subjects , 1968 .

[108]  A. Rechtschaffen.  A manual of Standardized Terminology , 1968 .

[109]  A. Beck,et al.  An inventory for measuring depression. , 1961, Archives of general psychiatry.

[110]  M. Hamilton.  A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.