Mild Cognitive Impairment and Obstructive Sleep Apnea

NCT01482351 | Completed Results DMC

• 2 other identifiers: 7584R01AG034682-01A2
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Obstructive Sleep Apnea; Mild Cognitive Impairment

Keywords

apnea; cognition; memory; function; amnestic mild cognitive impairment; older adults; Alzheimer's Disease

Outcome Measures

Primary Outcomes (6)

• Hopkins Verbal Learning Test-Revised (HVLT-R)

  Memory (immediate and delayed recall) will be assessed using HVLT-R. HVLT-R has been used in elders with Alzheimer's Disease and takes 10 minutes to complete. Total score ranges from 0 to 60, a higher score indicates a better memory (better outcome).

  Change from baseline at 6 months and 1 year

• Digit Symbol Subtest (DS)

  The Digit Symbol subtest (DS) from the Wechsler Adult Intelligence Scale (WAIS-R) was used to measure psychomotor/cognitive processing speed. An age-adjusted total scaled score was used for analysis. The adjusted total score ranges from -5.7 to+27. A higher score indicates a better outcome.

  Change from baseline at 6 months and 1 year

• Mini Mental State Evaluation Exam (MMSE)

  Global cognitive function will be assessed using MMSE. It is a 30-item cognitive screen measuring orientation, registration, short-term memory, attention/concentration, language, and constructional capacity. Summary score will be used as a measure of global cognitive function. Total score ranges from 0 to 30, equal to and above 24 is normal (better outcome), less than 21 indicates increasing odds of dementia (worse outcome).

  Change from baseline at 6 months and 1 year

• Stroop Color and Word Test (SCW)

  Attention will be measured using SCW. We used the Golden and Freshwater's (2002) version. This version provides paper stimuli for each trial: in the first, columns of the words"red""blue" and "green" are printed in black ink (Word Reading; W); in the second, columns of the same words are printed in red, blue, or green ink (Color Naming; C); in the third, the words "red" "blue" and "green" are printed in a colored ink (red, blue or green) that does not match the word (Color-Word; CW). Participants read each page aloud as quickly as possible for 45 seconds and receive a score for each trial representing the number of items correctly read aloud. The Interference T-score is obtained by first calculating a deviation score by subtracting a predicted CW score from the obtained raw CW score (in 45s). The obtained deviation score is then converted to an Interference T-score. Lower T scores(T\<40) in the Interference condition show reductions in inhibitory control.

  Change from baseline at 6 months and 1 year

• The Psychomotor Vigilance Task (PVT)

  Attention/reaction time will assessed using the PVT. The participants sat in a closed and quiet examination room, without any auditory or visual disturbance. A 1-minute mock PVT demonstration was done prior to each test. The PVT visual display was held 14-22 inches from the subject's eyes. The participants were asked to either use the index finger or thumb of their dominant hand to respond to the PVT signals. The participants were instructed to maintain the fastest possible reaction times to a simple visual stimulus: a red light emitting diode displaying time in milliseconds in a window of the portable PVT device. We used number of lapses, defined as mean reaction time above 500 milliseconds (errors of omission) as the primary outcome. Lower score indicates better outcomes (Less lapses).

  Change from baseline at 6 months and 1 year

• Epworth Sleepiness Scale [ESS]

  Daytime sleepiness be assessed using ESS. The ESS asks the respondent to rate the likelihood of falling asleep in eight specific situations using a four-point Likert scale ranging from never dozing to high chance of dozing. The scale significantly correlates with the frequency of apneas and is a clinical and research standard for the assessment of daytime sleepiness. The total score ranges from 0 to 24, a higher score indicates higher chance of daytime sleepiness (worse outcome).

  Change from baseline at 6 months and 1 year

Secondary Outcomes (4)

• Functional Outcomes Sleep Questionnaire (FOSQ)

  Change from baseline at 6 months and 1 year

• Everyday Function Outcome: Everyday Cognition (E-Cog)

  Change from baseline at 6 months and 1 year

• Alzheimer's Disease Cooperative Study - Clinicians' Global Impression of Change Scale (ADCS-CGIC)

  Change from baseline at 1 year

• Clinical Dementia Rating Scale (CDR)

  Change from baseline at 1 year

Study Arms (2)

MCI/OSA/CPAP Adherent

EXPERIMENTAL

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.

Behavioral: CPAP adherence intervention

MCI/OSA/CPAP Non-adherent

EXPERIMENTAL

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.

Behavioral: Attention control intervention

Interventions

CPAP adherence intervention 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 Adherent

Attention control intervention 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.

MCI/OSA/CPAP Non-adherent

Eligibility Criteria

• Age: 55 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• George Mason University: lead
• National Institute on Aging (NIA): collaborator
• University of Pennsylvania: collaborator

Study Sites (3)

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

George Mason University

Fairfax, Virginia, 22030, United States

Location

Related Publications (21)

• 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.

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• 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.

  PMID: 25878183 BACKGROUND

• 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.

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• 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.

  PMID: 26350607 BACKGROUND

• 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.

  PMID: 21652236 BACKGROUND

• 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.

  PMID: 20726284 BACKGROUND

• 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.

  PMID: 10190820 BACKGROUND

• 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.

  PMID: 12136057 BACKGROUND

• 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.

  PMID: 21744389 BACKGROUND

• 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.

  PMID: 8479064 BACKGROUND

• 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.

  PMID: 24826508 BACKGROUND

• 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.

  PMID: 24402217 BACKGROUND

• 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.

  PMID: 28162150 BACKGROUND

• 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.

  PMID: 21532951 BACKGROUND

• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

  PMID: 17166995 BACKGROUND

• 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.

  PMID: 30724333 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Cognitive Dysfunction; Apnea; Alzheimer Disease

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Limitations and Caveats

The study was not a randomized double-blind trial, and the sample is small. The groups may have been different on unidentified variables, and it is possible that these differences affected the study outcomes.

Results Point of Contact

• Title: Dr. Kathy C. Richards
• Organization: George Mason University

kricha11@gmu.edu

(703) 946-3725

Study Officials

• Kathy Richards, PhD, RN

  George Mason University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Persons collecting and analyzing neurocognitive data were blinded to participants' CPAP adherence.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: University Professor

Model Details: 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.

Study Record Dates

• First Submitted: November 28, 2011
• First Posted: November 30, 2011
• Study Start: September 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 6, 2019
• Results First Posted: January 29, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be made available 6 months after publication of the main study findings and will be available in perpetuity.
• Access Criteria: Individual participant data (IPD) will be publicly available via the following url

Locations

US (3)