Mild Cognitive Impairment and Obstructive Sleep Apnea

NCT ID: NCT01482351

Last Updated: 2019-03-06

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2014-12-31

Brief Summary

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Obstructive sleep apnea (OSA) has been linked to increased risk for Alzheimer's disease (AD), but little prospective evidence exists on the effects of OSA treatment in preclinical AD. The objective was to determine if CPAP treatment adherence, controlling for baseline differences, predicts cognitive and everyday function after 1 year in older adults with MCI and to determine effect sizes for a larger trial. The aim of the Mild Cognitive Impairment and Obstructive Sleep Apnea (Memories 1) trial was to determine whether CPAP treatment adherence, controlling for any baseline differences in OSA severity, ApoE4, and other previously identified demographic and patient factors, might predict cognitive and everyday function after 1 year in older adults with amnestic MCI.

Detailed Description

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In this prospective open label clinical trial, primary inclusions were age 55-89 years and apnea-hypopnea index ≥ 10. Groups were: (1) MCI, OSA, and CPAP adherent (MCI+CPAP); (2) MCI, OSA, CPAP nonadherent(MCI-CPAP). There were 68 MCI+OSA participants at baseline, and 14 (21%) dropped out during the 1 year follow-up. At 1 year, n=54, with MCI+CPAP group n=29, and MCI-CPAP group n=25. Statistically significant improvements in psychomotor/cognitive processing speed in the MCI+CPAP group versus the MCI-CPAP group were observed at 1 year after adjustment for age, race, and marital status. There were small to moderate effect sizes (ES) for memory, attention, daytime sleepiness, and everyday function, favoring the MCI+CPAP group versus the MCI-CPAP group.

Conditions

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Obstructive Sleep Apnea Mild Cognitive Impairment

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Memories 1 was originally designed as a 6-month double-blind randomized controlled pilot trial of active versus placebo CPAP followed by a 6-month open label trial. However, after 1 year of recruitment of 371 individuals, no one consented to be randomized. Both older adults with MCI and their physicians perceived the placebo arm as an unnecessary risk. Although CPAP eliminates OSA, it must be consistently used for at least 4 hours per night for a therapeutic response, and only 30-60% of individuals prescribed CPAP adhere to it. The investigators, the study Data Safety Monitoring Board, and the NIH approved a change to a quasi-experimental study with 2 comparison groups: 1) an MCI, OSA, and CPAP adherent group (MCI+CPAP, ≥4 hr mean CPAP use per night for 1 year); and (2) an MCI, OSA, CPAP non-adherent group (MCI-CPAP, \<4 hr mean CPAP use per night for 1 year). The final sample at 1 year consisted of 54 older adults with MCI: (1) MCI+CPAP, n = 29; and (2) MCI-CPAP, n = 25.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Persons collecting and analyzing neurocognitive data were blinded to participants' CPAP adherence.

Study Groups

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MCI/OSA/CPAP Adherent

Device: Continuous Positive Airway Pressure (CPAP). This arm included those diagnosed with mild cognitive impairment (MCI) and obstructive sleep apnea (OSA). The diagnostic criteria for OSA was defined as an Apnea Hypopnea Index (AHI) score of greater than or equal to 10. CPAP was prescribed for nightly use. Mean CPAP use in this arm was equal to or greater than 4 hours per night over one year. CPAP adherence Intervention was provided by research staff.

Group Type EXPERIMENTAL

CPAP adherence intervention

Intervention Type BEHAVIORAL

Critical factors were (1) OSA education, treatment expectations, and ways to minimize barriers and facilitate CPAP use; (2) promotion of a positive initial CPAP experience; (3) motivational interviewing to reinforce participants' health-related goals and CPAP self-efficacy; (4) anticipatory guidance and follow-up of common CPAP problems; and (5) social support by a study partner. Trained project staff provided the intervention by phone and face to face for a total of 12-14 hours over the 1 year project.

MCI/OSA/CPAP Non-adherent

Device: Continuous Positive Airway Pressure (CPAP). This arm included those diagnosed with mild cognitive impairment (MCI) and obstructive sleep apnea (OSA). The diagnostic criteria for OSA was defined as an Apnea Hypopnea Index (AHI) score of greater than or equal to 10. CPAP was prescribed for nightly use. Mean CPAP use in this arm was less than 4 hours per night or CPAP use was withdrew for any reason over one year. Attention control intervention was provided by staff.

Group Type EXPERIMENTAL

Attention control intervention

Intervention Type BEHAVIORAL

This intervention, provided by phone and face to face by project staff, provided equal time and attention. Critical factors were (1) education about OSA and risks, (2) education about memory, and other health topics of interest to the participants; (3) motivational interviewing to reinforce participants' health-related goals; (4) building rapport, and (5) social support by a study partner.

Interventions

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CPAP adherence intervention

Critical factors were (1) OSA education, treatment expectations, and ways to minimize barriers and facilitate CPAP use; (2) promotion of a positive initial CPAP experience; (3) motivational interviewing to reinforce participants' health-related goals and CPAP self-efficacy; (4) anticipatory guidance and follow-up of common CPAP problems; and (5) social support by a study partner. Trained project staff provided the intervention by phone and face to face for a total of 12-14 hours over the 1 year project.

Intervention Type BEHAVIORAL

Attention control intervention

This intervention, provided by phone and face to face by project staff, provided equal time and attention. Critical factors were (1) education about OSA and risks, (2) education about memory, and other health topics of interest to the participants; (3) motivational interviewing to reinforce participants' health-related goals; (4) building rapport, and (5) social support by a study partner.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

Participants are included in the study if all of the following criteria are met:

(1) Are able to provide written informed consent by self or legally authorized representative. MacArthur Competency Assessment Tool for Clinical Research (MacCAT-CR) will be used to assess decision making capacity; (2) OSA defined as an apnea-hypopnea index (AHI) ≥10, using either a clinical split- or whole-night polysomnography. We chose an AHI cut-off of ≥10 as opposed to ≥15, the conventional cut-off for moderate OSA because split-night studies underestimate the AHI; (3) education-adjusted scores of 28-35 on the modified Telephone Interview for Cognitive Status; (4) 0-0.5 on the Clinical Dementia Rating (CDR); (5) 24-30 on the Mini-Mental State Examination (MMSE); (6) memory impairment approximately 1.0-1.5 standard deviations below normal (adjusted for age and education), determined by scores on the Logical Memory II test; (7) performance approximately 1.0-1.5 standard deviations below normal (adjusted for age and education) in no more than one cognitive domain in addition to memory; (8) medications stable for at least 4 weeks; washout from psychoactive medications (e.g., excluded anti-depressants, neuroleptics, chronic anxiolytics, and sedative hypnotics) for 4 weeks; (9) score of ≤28 on the 21-item Beck Depression Inventory II; (10) a study partner who spends at least 10 hours per week in phone or in-person contact with participant; (11) visual and auditory acuity for testing; (12) 6 or more grades of education completed, or a history to exclude intellectual disability; and (13) English fluency.

Exclusion Criteria

Patients are excluded from participating in this study if 1 or more of the following criteria are met:

(1) significant neurologic disease other than MCI; (2) MRI exclusions, e.g. metal; (3) psychiatric disorders, including uncontrolled major depression, bipolar disorder, or schizophrenia; (4) history of alcohol dependence within 6 months; (5) current significant unstable medical condition; (6) participation in studies involving neuropsychological testing; (7) currently receiving CPAP; (8) requiring oxygen during CPAP; (9) dementia indicated by impairment in 3-5 age and education adjusted cognitive domains.
Minimum Eligible Age

55 Years

Maximum Eligible Age

89 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role collaborator

George Mason University

OTHER

Sponsor Role lead

Responsible Party

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Kathy C. Richards

University Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kathy Richards, PhD, RN

Role: PRINCIPAL_INVESTIGATOR

George Mason University

Locations

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Abington Memorial Hospital

Abington, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

George Mason University

Fairfax, Virginia, United States

Site Status

Countries

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United States

References

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Terpening Z, Lewis SJ, Yee BJ, Grunstein RR, Hickie IB, Naismith SL. Association between Sleep-Disordered Breathing and Neuropsychological Performance in Older Adults with Mild Cognitive Impairment. J Alzheimers Dis. 2015;46(1):157-65. doi: 10.3233/JAD-141860.

Reference Type BACKGROUND
PMID: 25720400 (View on PubMed)

Osorio RS, Gumb T, Pirraglia E, Varga AW, Lu SE, Lim J, Wohlleber ME, Ducca EL, Koushyk V, Glodzik L, Mosconi L, Ayappa I, Rapoport DM, de Leon MJ; Alzheimer's Disease Neuroimaging Initiative. Sleep-disordered breathing advances cognitive decline in the elderly. Neurology. 2015 May 12;84(19):1964-71. doi: 10.1212/WNL.0000000000001566. Epub 2015 Apr 15.

Reference Type BACKGROUND
PMID: 25878183 (View on PubMed)

Guarnieri B, Adorni F, Musicco M, Appollonio I, Bonanni E, Caffarra P, Caltagirone C, Cerroni G, Concari L, Cosentino FI, Ferrara S, Fermi S, Ferri R, Gelosa G, Lombardi G, Mazzei D, Mearelli S, Morrone E, Murri L, Nobili FM, Passero S, Perri R, Rocchi R, Sucapane P, Tognoni G, Zabberoni S, Sorbi S. Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients. Dement Geriatr Cogn Disord. 2012;33(1):50-8. doi: 10.1159/000335363. Epub 2012 Mar 8.

Reference Type BACKGROUND
PMID: 22415141 (View on PubMed)

Dzierzewski JM, Wallace DM, Wohlgemuth WK. Adherence to Continuous Positive Airway Pressure in Existing Users: Self-Efficacy Enhances the Association between Continuous Positive Airway Pressure and Adherence. J Clin Sleep Med. 2016 Feb;12(2):169-76. doi: 10.5664/jcsm.5478.

Reference Type BACKGROUND
PMID: 26350607 (View on PubMed)

Sawyer AM, Gooneratne NS, Marcus CL, Ofer D, Richards KC, Weaver TE. A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions. Sleep Med Rev. 2011 Dec;15(6):343-56. doi: 10.1016/j.smrv.2011.01.003. Epub 2011 Jun 8.

Reference Type BACKGROUND
PMID: 21652236 (View on PubMed)

Khawaja IS, Olson EJ, van der Walt C, Bukartyk J, Somers V, Dierkhising R, Morgenthaler TI. Diagnostic accuracy of split-night polysomnograms. J Clin Sleep Med. 2010 Aug 15;6(4):357-62.

Reference Type BACKGROUND
PMID: 20726284 (View on PubMed)

Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999 Mar;56(3):303-8. doi: 10.1001/archneur.56.3.303.

Reference Type BACKGROUND
PMID: 10190820 (View on PubMed)

Bennett DA, Wilson RS, Schneider JA, Evans DA, Beckett LA, Aggarwal NT, Barnes LL, Fox JH, Bach J. Natural history of mild cognitive impairment in older persons. Neurology. 2002 Jul 23;59(2):198-205. doi: 10.1212/wnl.59.2.198.

Reference Type BACKGROUND
PMID: 12136057 (View on PubMed)

Rosness TA, Haugen PK, Engedal K. The clinical dementia rating scale could be helpful in differentiating frontotemporal dementia from Alzheimer's disease. Int J Geriatr Psychiatry. 2011 Aug;26(8):879-80. doi: 10.1002/gps.2555. No abstract available.

Reference Type BACKGROUND
PMID: 21744389 (View on PubMed)

Crum RM, Anthony JC, Bassett SS, Folstein MF. Population-based norms for the Mini-Mental State Examination by age and educational level. JAMA. 1993 May 12;269(18):2386-91.

Reference Type BACKGROUND
PMID: 8479064 (View on PubMed)

Morris J, Swier-Vosnos A, Woodworth C, Umfleet LG, Czipri S, Kopald B. Development of alternate paragraphs for the Logical Memory subtest of the Wechsler Memory Scale-IV. Appl Neuropsychol Adult. 2014;21(2):143-7. doi: 10.1080/09084282.2013.780172. Epub 2013 Sep 11.

Reference Type BACKGROUND
PMID: 24826508 (View on PubMed)

Wang YP, Gorenstein C. Psychometric properties of the Beck Depression Inventory-II: a comprehensive review. Braz J Psychiatry. 2013 Oct-Dec;35(4):416-31. doi: 10.1590/1516-4446-2012-1048. Epub 2013 Dec 23.

Reference Type BACKGROUND
PMID: 24402217 (View on PubMed)

Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, Harrod CG. Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017 Mar 15;13(3):479-504. doi: 10.5664/jcsm.6506.

Reference Type BACKGROUND
PMID: 28162150 (View on PubMed)

Basner M, Dinges DF. Maximizing sensitivity of the psychomotor vigilance test (PVT) to sleep loss. Sleep. 2011 May 1;34(5):581-91. doi: 10.1093/sleep/34.5.581.

Reference Type BACKGROUND
PMID: 21532951 (View on PubMed)

Tomaszewski Farias S, Mungas D, Harvey DJ, Simmons A, Reed BR, Decarli C. The measurement of everyday cognition: development and validation of a short form of the Everyday Cognition scales. Alzheimers Dement. 2011 Nov;7(6):593-601. doi: 10.1016/j.jalz.2011.02.007.

Reference Type BACKGROUND
PMID: 22055976 (View on PubMed)

Billings ME, Rosen CL, Auckley D, Benca R, Foldvary-Schaefer N, Iber C, Zee PC, Redline S, Kapur VK. Psychometric performance and responsiveness of the functional outcomes of sleep questionnaire and sleep apnea quality of life instrument in a randomized trial: the HomePAP study. Sleep. 2014 Dec 1;37(12):2017-24. doi: 10.5665/sleep.4262.

Reference Type BACKGROUND
PMID: 25325491 (View on PubMed)

Schwartz SW, Sebastiao Y, Rosas J, Iannacone MR, Foulis PR, Anderson WM. Racial disparity in adherence to positive airway pressure among US veterans. Sleep Breath. 2016 Sep;20(3):947-55. doi: 10.1007/s11325-016-1316-1. Epub 2016 Jan 25.

Reference Type BACKGROUND
PMID: 26810493 (View on PubMed)

Hakansson K, Rovio S, Helkala EL, Vilska AR, Winblad B, Soininen H, Nissinen A, Mohammed AH, Kivipelto M. Association between mid-life marital status and cognitive function in later life: population based cohort study. BMJ. 2009 Jul 2;339:b2462. doi: 10.1136/bmj.b2462.

Reference Type BACKGROUND
PMID: 19574312 (View on PubMed)

Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the challenge to effective treatment. Proc Am Thorac Soc. 2008 Feb 15;5(2):173-8. doi: 10.1513/pats.200708-119MG.

Reference Type BACKGROUND
PMID: 18250209 (View on PubMed)

Zimmerman ME, Arnedt JT, Stanchina M, Millman RP, Aloia MS. Normalization of memory performance and positive airway pressure adherence in memory-impaired patients with obstructive sleep apnea. Chest. 2006 Dec;130(6):1772-8. doi: 10.1378/chest.130.6.1772.

Reference Type BACKGROUND
PMID: 17166995 (View on PubMed)

Richards KC, Gooneratne N, Dicicco B, Hanlon A, Moelter S, Onen F, Wang Y, Sawyer A, Weaver T, Lozano A, Carter P, Johnson J. CPAP Adherence May Slow 1-Year Cognitive Decline in Older Adults with Mild Cognitive Impairment and Apnea. J Am Geriatr Soc. 2019 Mar;67(3):558-564. doi: 10.1111/jgs.15758. Epub 2019 Feb 6.

Reference Type DERIVED
PMID: 30724333 (View on PubMed)

Other Identifiers

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R01AG034682-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

7584

Identifier Type: -

Identifier Source: org_study_id

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