Neuropsychological Effects of One-Week Continuous Positive Airway Pressure Treatment in Patients With Obstructive Sleep Apnea: A Placebo-Controlled Study WAYNE A. BARDWELL,PHD, SONIA ANCOLI-ISRAEL,PHD, CHARLES C. BERRY,PHD, AND JOEL E. DIMSDALE, MD Objective: To determine whether 1-week continuous positive airway pressure (CPAP) treatment, compared with placebo CPAP, improves cognitive functioning in patients with obstructive sleep apnea (OSA). Methods: 36 OSA patients (aged 32– 60 years, respiratory disturbance index [RDI]  15) were monitored 2 nights with polysomnog- raphy, then randomized for 1-week treatment to CPAP or placebo (CPAP at 2 cm H 2 O with holes in mask). Participants completed Wechsler Adult Intelligence Scale—Revised Digit Symbol and Digit Span, Trailmaking A/B, Digit Vigilance, Stroop Color-Word, Digit Ordering, and Word Fluency tests pre- and posttreatment. These produced 22 scores per participant, which were analyzed by use of repeated-measures analysis of variance (ANOVA) and a rank-sum test. Results: In ANOVA, only 1 of the 22 scores showed significant changes specific to CPAP treatment, a number that could be expected by chance alone: Digit Vigilance-Time (p = .035). The CPAP group improved their time (from 7.5 to 6.9 minutes, p = .013). The rank-sum test revealed that the CPAP group had significantly better overall cognitive functioning posttreatment than the placebo group (mean ranks of 17.8 vs. 20.2, respectively; p = .022). Conclusions: Although results suggest overall cognitive improvement due to CPAP, no beneficial effects in any specific cognitive domain were found. Future studies of neuropsychological effects of CPAP treatment should include a placebo CPAP control group. Placebo studies that use longer-term treatment might demonstrate additional effects. It is also possible that, even at 2 cm H 2 O, CPAP conveys some beneficial neuropsychological effects. Key words: apnea, CPAP, neuropsychological functioning, cognitive deficits. AHI = apnea/hypopnea index; ANOVA = analysis of variance; BMI = body mass index; BP = blood pres- sure; CABG = coronary artery bypass graft; COPD = chronic obstructive pulmonary disease; CPAP = con- tinuous positive airway pressure; O 2 = oxygen; PSG = polysomnography; RDI = respiratory disturbance in- dex; REM = rapid eye movement; SD = standard de- viation; WAIS = Wechsler Adult Intelligence Scale. Obstructive sleep apnea (OSA) can be a devastating illness, leaving patients exhausted from sleep depriva- tion and sometimes cognitively impaired (1). Research results are mixed, however, regarding the nature and cause of cognitive deficits in these patients. In 18 studies of cognitive functioning in patients with OSA, all found some impairment (2–17), although the type of impairment observed varied greatly. Most com- monly reported were deficits in global cognitive func- tioning (2–5), memory (6 –11, 17), attention (2, 3, 12, 13), and concentration (2, 7, 17). Six studies compared OSA with other disorders that have a breathing or sleep component (eg, chronic obstructive pulmonary disease or narcolepsy), with four reporting greater cog- nitive impairment in patients having OSA (7, 8, 11, 13) and two finding no differences between conditions (14, 18). Among studies examining the impact of OSA treatment (mainly CPAP) on cognitive functioning, most have reported at least some improvement (9, 16, 19 –21), although one did not (22). Again, the specific areas of cognitive improvement varied greatly. In summary, most but not all of the cited studies found cognitive impairment in OSA. However, tests used to assess cognitive functioning varied greatly. This impairment seems to be exacerbated by the level of hypoxemia (2– 4, 6, 9, 12, 23), RDI (6, 7, 9, 23), and arousals (6). Most research that has examined cogni- tive functioning pre– and post–CPAP treatment has reported significant but inconsistent improvements. Some authors have speculated that neuropsychologi- cal functions that have not shown improvement may be due to cerebral damage from hypoxemia. Therefore, instrument selection and differences between patient groups regarding the presence of hypoxemia and de- gree of OSA severity may contribute to disparities in the literature. The purpose of the present study was to evaluate the effectiveness of CPAP treatment vs. placebo CPAP (at insufficient pressure) on cognitive functioning in pa- tients with OSA. CPAP, by nature, is an obvious inter- vention, and controlled studies are rare. Some have compared CPAP against nontreatment or medication controls, and, recently, two other groups, like ours, used some form of placebo CPAP (24, 25). However, we are unaware of any studies that have used a cred- ible CPAP placebo in an analysis of cognitive function- ing. Placebo CPAP has the advantage of duplicating the mask, airflow, and equipment presence and sounds without having a major impact on RDI. From the University of California, San Diego, Departments of Psychiatry (W.A.B., S.A.-I., J.E.D.) and Family and Preventive Med- icine (C.C.B.); and Veterans Affairs San Diego Healthcare System (W.A.B., S.A.-I.), San Diego, California. Address reprint requests to: Wayne A. Bardwell, PhD, University of California, San Diego, Department of Psychiatry-0804, 9500 Gil- man Drive, La Jolla, CA 92093-0804. Email: wabardwell@ucsd.edu Received for publication May 3, 2000; revision received Novem- ber 13, 2000. 579 Psychosomatic Medicine 63:579 –584 (2001) 0033-3174/01/6304-0579 Copyright © 2001 by the American Psychosomatic Society