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Adherence to continuous positive airway pressure treatment in patients with Alzheimer's disease and obstructive sleep apnea

This analysis examined whether patients with Alzheimer disease (AD) tolerate continuous positive airway pressure (CPAP). Thirty patients with AD were randomized to CPAP or sham CPAP and completed sleep, depression, and quality-of-life questionnaires.
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   Adherence to ContinuousPositive Airway Pressure Treatment in Patients With  Alzheimer Disease and Obstructive Sleep Apnea   Liat Ayalon, Ph.D. Sonia Ancoli-Israel, Ph.D. Carl Stepnowsky, Ph.D. Matthew Marler, Ph.D. Barton W. Palmer, Ph.D. Lianqi Liu, M.D.  Jose S. Loredo, M.D.  Jody Corey-Bloom, M.D. Deborah Greenfield, M.A.  Jana Cooke, M.D. Objective:  This analysis examined whether patientswith Alzheimer disease (AD) tolerate continuous pos- itive airway pressure (CPAP).  Method:  Thirty pa- tients with AD were randomized to CPAP or shamCPAP and completed sleep, depression, and quality- of-life questionnaires. Participants could choose tocontinue treatment after the trial.  Results:  Patientswore CPAP for 4.8 hours per night. More depressive symptoms were associated with worse adherence (r  S   0.37; N    30, p  0.04). Patients who continued using CPAP had fewer depressive symptoms (t [19]    2.45, p  0.02) and better adherence (t [19]    2.32, p   0.03) during the trial.  Conclusion:  Patients with AD with obstructive sleep apnea can tolerate CPAP. Adherence and long-term use may be more difficult among those patients with more depressive symp- toms.  (Am J Geriatr Psychiatry 2006; 14:176–180) Key Words:  Sleep apnea, CPAP, Alzheimer disease,adherence O  bstructive sleep apnea (OSA) is characterized by repeated cessations of breathing duringsleep, which result in some potentially serious con-sequences, including neurocognitive impairment.OSA is very prevalent in older adults 1 and in pa-tients with Alzheimer disease (AD). 2 OSA is treated with nasal continuous positive air-way pressure (CPAP). Aloia et al. 3 found that three-months of compliant CPAP use in cognitively intactolder adults resulted in improved attention, psy-chomotor speed, executive functioning, and nonver- bal delayed recall. Despite the documented efficacyof CPAP, it is estimated that over 50% of thosestarted on CPAP will not be using it one year later. 4 Adherence rates range from 3.3 to 5.3 hours pernight. 5 Although determinants of CPAP adherenceare not well understood, depression has been asso-ciated with treatment nonadherence. 6 Because CPAP has been shown to improve cogni-tive functioning in patients with OSA and becauseOSA is very common in dementia, this study exam-ined whether patients with AD would tolerateCPAP. Based on data described here, 6 a secondaryaim was whether lower CPAP adherence is related todepression. METHODS Subjects Thirty patients (23 male; 94% white; mean age: 78.4years, standard deviation [SD]: 6.8, range: 53–91;mean body mass index: 24.7, SD: 3.7, range: 20.4–40.7; mean education: 14.8 years, SD: 3.1, range:8–20) participated in a larger study evaluating theeffect of CPAP on cognitive functioning in patientswith mild-to-moderate AD and OSA. Patients wererecruited from the University of California San Di-ego, CA (UCSD) Alzheimer’s Disease Research Cen- Received November 14, 2004; revised March 25, 2005; accepted March 29, 2005. From the Department of Psychiatry (LA, SA-I, MM, BWP, LL,DG), University of California, San Diego, San Diego, CA, Veterans Affairs San Diego Health Care System (LA, SA-I, CS, LL, JSL, JC-B, DG, JC), theDepartment of Medicine (JSL, JC), University of California, San Diego, San Diego, CA, and the Department of Neurosciences (JC-B), University of California, San Diego, San Diego, CA. Send correspondence and reprint requests to Sonia Ancoli-Israel, Ph.D., Department of Psychiatry 116A, VASDHS, 3350 La Jolla Village Dr., San Diego, CA 92161. e-mail:© 2006 American Association for Geriatric Psychiatry   Am J Geriatr Psychiatry 14:2, February 2006176  BRIEF REPORTS  ter (ADRC), advertisements, and referrals. All sub- jects and caregivers signed consent forms approved by the UCSD Committee for the Protection of Hu-man Subjects.Inclusion criteria included being 50 years of age,possible or probable mild-to-moderate AD (diag-nosed by a neurologist according to the NationalInstitute of Neurological and Communicative Disor-ders & Stroke–Alzheimer’s Disease and Related Dis-orders Association [NINCDS-ADRDA] criteria), aMini-Mental Status Examination (MMSE) of    18,OSA of   10 documented respiratory events per hourof sleep, English-speaking, stable health, and a reli-able live-in caregiver. Subjects were allowed to con-tinue acetylcholinesterase inhibitors, psychotropicmedications, memory enhancers, and health foodsupplements as long as they had been stable on thesame dose for at least two months before participa-tion and continued on the same dose for the durationof the study.Because the study included treatment for OSA,exclusion criteria included currently receiving treat-ment for OSA, a history of central apneas or othersleep disorders, taking medications known to influ-ence sleep, moderate chronic obstructive pulmonarydisease, or a history of CO 2  retention, symptomaticcoronary or cerebral vascular disease, history of life-threatening arrhythmias, and cardiomyopathy. Sub- jects were also excluded if they had a history of psychosis, current alcohol or drug abuse, an active,uncontrolled seizure disorder, or any other ad-vanced, severe, and unstable disease that would putthem at special risk or interfere with primary andsecondary variable evaluations. Procedure Questionnaires.  Caregivers and patients togethercompleted questionnaires about sleep, mood, andquality of life. Questionnaire data were collected at baseline, after three weeks, and after six weeks of CPAP use.The Pittsburgh Sleep Quality Index (PSQI), 7 a 19-item questionnaire, was used to evaluate subjectivereports of sleep quality and quantity, specificallysubjective sleep quality, sleep latency, sleep dura-tion, habitual sleep efficiency, sleep disturbances, useof sleep medication, and daytime dysfunction. TotalPSQI scores range from zero to 21 with high scoresreflecting poor sleep quality. A score above five isconsidered poor sleep.The Epworth Sleepiness Scale (ESS) 8 was used torate the likelihood of falling asleep in different situ-ations on a scale of zero (no chance of falling asleep)to three (high likelihood of falling asleep). A score of 10 or above is considered pathologic daytime sleep-iness.The Functional Outcomes of Sleep Questionnaire(FOSQ) 9 was used to measure functional status insituations that produce sleepiness. The FOSQ hasfive subscales: vigilance, intimacy and sexual rela-tionships, general productivity, activity level, andsocial outcome. A score below 18 is considered func-tionalimpairment,withlowerscoresindicatingmoredysfunction.The Cornell Scale for Depression (CSD) in Demen-tia, a 19-item questionnaire, was used to assessmood. 10 The CSD has five categories: mood-relatedsymptoms, behavioral disturbance, physical signs,cyclic functions, and ideational disturbance. Higherscores are suggestive of more depressive symptomsand a total score above six is considered clinicallysignificant for patients with AD. Continuous Positive Airway Pressure.  Patientswereadmitted to the UCSD General Clinical ResearchCenter (GCRC) Gillin Laboratory of Sleep and Chro-nobiology (LSC) for two nights and were random-ized to traditional CPAP treatment (N  14) or shamCPAP treatment (N  16). The sham CPAP consistedof a CPAP mask containing 10-1/4-inch drill holes,and a pressure reducer (reproducing the normalCPAP mask air leak placed between the output tubeof the heated humidifier and the connecting tube tothe CPAP mask). To control for CPAP blower noise,the pressure was set at 8 cm H 2 O. The multiple drillholes allowed for adequate air exchange, thus pre-venting rebreathing. With this system, the pressureat the CPAP mask varied from 0.5 cm H 2 O at endexpiration to 0.0 cm H 2 O during inspiration, and thepatient experienced a gentle air breeze at the nose.On the first night, a CPAP mask was fitted and both patient and caregiver were trained on the use of the CPAP (Remstar Pro CPAP; Respironics, Pitts- burgh, PA) and heated humidifier (HC150 Respira-tory Humidifier; Fisher & Paykel, Auckland, NewZealand). Patients were given ample opportunity topractice wearing the mask. A full polysomnogram  Ayalon et al.  Am J Geriatr Psychiatry 14:2, February 2006 177  (PSG) was obtained (Embla; Flaga Medical Devices/Medcare, Reykjavik, Iceland). For the CPAP group,CPAP was titrated to establish therapeutic pressureat which both apneas and hypopneas and sleep dis-ruption were reduced to the lowest possible levels(i.e., optimal therapeutic pressure). Sham CPAP sub- jects underwent a mock titration. On the secondnight, all subjects slept with the CPAP pressure set tolevels determined on night one. In the morning, pa-tients were discharged and sent home for threeweeks with their CPAP machine.At the end of three weeks, patients returned to theGCRC LSC for two additional nights of sleep record-ings. On the first night, patients in the sham CPAPgroup had their CPAP mask switched to a new intactmask and underwent standard CPAP titration to theoptimal therapeutic pressure. For patients in the realCPAP group, pressure was checked and adjusted.On the second night, all patients used the CPAPmachine, again set at the predetermined level. In themorning,patientsweredischargedandsenthomewiththeir CPAP machine for another three weeks. Anotherhome PSG was conducted at the end of the study.During the six weeks of treatment, patients werecontacted on a regular basis. If any problems werereported, the research assistant made visits to theirhomes. Common problems included complaintsabout how the mask felt or the noise of the CPAPmachine.Adherence with CPAP therapy was monitored byhidden clocks that counted number of hours thecompressor was switched on and the CPAP pressurewas within 2 cm H 2 O of the prescribed pressure.AdherencedatafromthefirstthreeweeksfortherealCPAP group and from the last three weeks for shamCPAP group were used in analyses. Postprotocol Continuous Positive Airway PressureContinuation.  Within 1–10 months (mean: 4.8months, SD: 2.8) after study completion, patientswere contacted to determine if they had continuedusing CPAP. Statistical Analysis.  Spearman correlations werecomputed between average hours of CPAP use pernight during the three weeks of real CPAP (i.e., thefirst three weeks for the real CPAP group and thesecond three weeks for the sham CPAP group) andthe following variables collected at baseline: sleepquestionnaires (FOSQ, PSQI, ESS), mood (CSD), de-mentia (MMSE), and demographics (age, body massindex, education).Student  t -tests were used to compare those pa-tients who continued using CPAP with those whowere no longer using CPAP at the time of the fol-low-up phone interview. The two groups were com-pared on reported sleep variables (FOSQ, PSQI, ESS),mood (CSD), dementia (MMSE), and demographics(age, body mass index, education). When the twogroups had different variances, the Mann-Whitneytest was used.Because the analysis tested the a priori hypothesisthat depression was related to adherence, unlike therest of the measurements, statistics related to thedepression measure were not subjected to a Bonfer-roni correction. RESULTS Subject Characteristics.  Therewerenosignificantdif-ferences between patients in the two groups in initialnumber of respiratory events ( t [28]  0.19, p  0.84).The mean AHI for the full group at initial evaluationwas 25.6 (SD: 14.1, range: 11–76.4). There were nosignificant differences between groups in initialMMSE (total group mean: 25.3, SD: 3.0, range: 18–30), depression (CSD total group mean: 4.8, SD: 3.9,range: 0–14), self-reports of sleep (PSQI total groupmean: 4.7, SD: 3.0, range: 1–13), daytime sleepiness(ESS total group mean: 8.6, SD: 4.5, range: 0–16), orfunctional outcome (FOSQ total group mean: 18.3,SD: 1.3, range: 15.1–19.9). Continuous Positive Airway Pressure Adherence. There were no significant differences in hours of CPAP use between patients in the two groups(Mann-Whitney U  76, n 1  16 [sham CPAP], n 2  14 [CPAP], p  0.14). The mean number of hours of CPAP use per night for the entire group was 4.8hours (SD: 2.0; range: 0.3–8.34). Factors Related to Continuous Positive Airway Pressure Adherence Spearman correlations between hours of CPAP useper night and the demographic variables, sleep andmood questionnaires, and dementia ratings weretested. All p values were   0.25 except for the CSD  Adherence to CPAP Treatment in Patients with AD and OSA  Am J Geriatr Psychiatry 14:2, February 2006178  with those with fewer depressive symptoms having better adherence (r S  0.37; N  30, p  0.04). TheCPAP and sham CPAP groups did not differ ondepression at the end of the first three weeks (t   0.58, df   28, p  0.58). Continuous Positive Airway PressureContinuation  CPAP continuation data were available for 21 (17male) patients. Of these, nine patients continued us-ing CPAP after completion of the study. Student t -tests comparing baseline values of those continuingCPAP (N    9) versus not continuing (N    12) re-vealed that they differed only in their baseline CSDscores with the CPAP continuation group (meanCSD: 2.3, SD: 2.8, range: 0–8) having fewer depres-sive symptoms than the noncontinuation group(mean CSD: 6.7, SD: 4.6, range: 0–14;  t [19]  2.45, p   0.02) (Figure 1). Patients who continued usingCPAP also had significantly higher CPAP adherenceduring the srcinal three-week treatment (mean: 5.5hours/night, SD: 1.5; range: 2.8–7.7) than those whodid not continue (mean: 3.7 hours/night, SD: 1.8,range: 0.8–6.0) ( t [19]  2.32, p  0.03). DISCUSSION To our knowledge, this is the first study to suggestthat patients with AD who have OSA can use CPAPwith reasonable adherence. Adherence with CPAPtherapy in uncomplicated OSA has been marginal at best. It was surprising that the average number of hours of CPAP use per night in the patients with AD,4.8 hours, was not very different from the number of hours reported in sleep disorders clinic patients. 5 Because there can be beneficial effects of treatingOSA on the cardiovascular system, mood, and qual-ity of life, and perhaps cognition, it is important thatclinicians do not rule out treating OSA in patientswith AD just because of the dementia.Understanding of the determinants of CPAP ad-herence is just emerging. Substantial evidence fromthe literature on treatment adherence in otherchronic conditions suggests that depression maynegatively impact treatment adherence. 6 In this-study, although patients in general were not clini-cally depressed, those with fewer depressive symp-toms had significantly higher adherence. In addition,those patients who continued to use CPAP after theend of the study had less severe depressive symp-toms at baseline. Patients with less depressive symp-toms may do better in adjusting and may havehigher motivation to improve their sleep and qualityof life than those with more depressive symptoms.In summary, this study showed that patients withmild-to-moderate AD were able to tolerate CPAP.The presence of mild-to-moderate dementia shouldnot be a deterrent to the use of CPAP to treat OSA inpatients who have a full-time caregiver. The authors acknowledge support from National In-stitue on Aging AG08415, National Institute of Mental Health 5 T32 MH18399-17, National Institute of HealthGeneral Clinical Research Center M01 RR00827, Na-tional Institute of Aging P50 AG05131, Veterans Affairs Health Services Research & Development Service 02-275,and the research service of the Veterans Affairs SanDiego Healthcare System. FIGURE 1. Pretreatment Score on the Cornell Scale of Depression for Those Who Did and Did Not Continue Using CPAP After the End of the Study Protocol   Note:  *Dotted line represents the cutoff for clinically significantdepression in patients with AD.CPAP: continuous positive airway pressure; AD: Alzheimer disease.  Ayalon et al.  Am J Geriatr Psychiatry 14:2, February 2006 179  References 1. Ancoli-Israel S, Kripke DF, Klauber MR, et al: Sleep disorderedbreathing in community-dwelling elderly. Sleep 1991; 14:486–4952. Gehrman PR, Martin JL, Shochat T, et al: Sleep disordered breath-ing and agitation in institutionalized adults with Alzheimer’sdisease. Am J Geriatr Psychiatry 2003; 11:426–4333. Aloia MS, Ilniczky N, Di Dio P, et al: Neuropsychological changesand treatment compliance in older adults with sleep apnea. JPsychosom Res 2003; 54:71–764. 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Biol Psychiatry 1988; 23:271–284  Adherence to CPAP Treatment in Patients with AD and OSA  Am J Geriatr Psychiatry 14:2, February 2006180
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