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Mild Cognitive Impairment and Obstructive Sleep Apnea (MEMORIES)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01482351
Recruitment Status : Completed
First Posted : November 30, 2011
Results First Posted : January 29, 2019
Last Update Posted : March 6, 2019
Sponsor:
Collaborators:
National Institute on Aging (NIA)
University of Pennsylvania
Information provided by (Responsible Party):
Kathy C. Richards, George Mason University

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.

Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnea Mild Cognitive Impairment Behavioral: CPAP adherence intervention Behavioral: Attention control intervention Not Applicable

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Single (Outcomes Assessor)
Masking Description: Persons collecting and analyzing neurocognitive data were blinded to participants' CPAP adherence.
Primary Purpose: Treatment
Official Title: Mild Cognitive Impairment and Obstructive Sleep Apnea
Study Start Date : September 2012
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory Sleep Apnea

Arm Intervention/treatment
Experimental: 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.
Behavioral: 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.

Experimental: 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.
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.




Primary Outcome Measures :
  1. Hopkins Verbal Learning Test-Revised (HVLT-R) [ Time Frame: Change from baseline at 6 months and 1 year ]
    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).

  2. Digit Symbol Subtest (DS) [ Time Frame: Change from baseline at 6 months and 1 year ]
    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.

  3. Mini Mental State Evaluation Exam (MMSE) [ Time Frame: Change from baseline at 6 months and 1 year ]
    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).

  4. Stroop Color and Word Test (SCW) [ Time Frame: Change from baseline at 6 months and 1 year ]
    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.

  5. The Psychomotor Vigilance Task (PVT) [ Time Frame: Change from baseline at 6 months and 1 year ]
    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).

  6. Epworth Sleepiness Scale [ESS] [ Time Frame: Change from baseline at 6 months and 1 year ]
    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).


Secondary Outcome Measures :
  1. Functional Outcomes Sleep Questionnaire (FOSQ) [ Time Frame: Change from baseline at 6 months and 1 year ]
    Everyday function will be assessed using FOSQ. It is a 30-item Likert-scale, self-report, disease-specific functional status measure written at the 4th grade level. The total score ranges from 0 to 120, a higher score indicates a better outcome.

  2. Everyday Function Outcome: Everyday Cognition (E-Cog) [ Time Frame: Change from baseline at 6 months and 1 year ]
    This informant-rated composes of multiple subscales, to evaluate cognitively based functional abilities in older adults. The factor structure of Everyday Cognition was assessed with confirmatory factor analysis, which supported a 7-factor model including 1 global factor and 6 domain-specific factors (Everyday Memory, Language, Visuospatial Abilities, Planning, Organization, and Divided Attention). The total mean score ranges from 0 to 57. A higher score indicates a worse outcome.

  3. Alzheimer's Disease Cooperative Study - Clinicians' Global Impression of Change Scale (ADCS-CGIC) [ Time Frame: Change from baseline at 1 year ]
    Global change (progression) will be assessed using ADCS-CGIC at 1 year. It has 8 categories as markedly improved, moderately improved, minimally improved, not changed, minimally worse, moderately worse, markedly worse, missing response.

  4. Clinical Dementia Rating Scale (CDR) [ Time Frame: Change from baseline at 1 year ]
    Cognitive ability will be assessed and staged using CDR. It contains 6 items (memory, orientation, judgement and problem solving, community affairs, home and hobbies, personal care), and each item ranges from 0 to 3. The total score ranges from 0 to 18, a higher score indicates a worse outcome. We observed the change of CDR score from baseline to 1-year follow up. Improved on CDR was defined as a lower CDR score compared to baseline. Reference group is unimproved, defined as worsened (higher) CDR or unchanged CDR compared to baseline.



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Ages Eligible for Study:   55 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01482351


Locations
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United States, Pennsylvania
Abington Memorial Hospital
Abington, Pennsylvania, United States, 19001
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Virginia
George Mason University
Fairfax, Virginia, United States, 22030
Sponsors and Collaborators
George Mason University
National Institute on Aging (NIA)
University of Pennsylvania
Investigators
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Principal Investigator: Kathy Richards, PhD, RN George Mason University
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kathy C. Richards, University Professor, George Mason University
ClinicalTrials.gov Identifier: NCT01482351    
Other Study ID Numbers: 7584
R01AG034682-01A2 ( U.S. NIH Grant/Contract )
First Posted: November 30, 2011    Key Record Dates
Results First Posted: January 29, 2019
Last Update Posted: March 6, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data have been prepared for sharing with other investigators. Data can be accessed at http://dx.doi.org/10.15139/S3/12081 after publication of the main study findings.
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
URL: http://dx.doi.org/10.15139/S3/12081
Keywords provided by Kathy C. Richards, George Mason University:
apnea
cognition
memory
function
amnestic mild cognitive impairment
older adults
Alzheimer's Disease
Additional relevant MeSH terms:
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Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Cognitive Dysfunction
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Cognition Disorders
Neurocognitive Disorders
Mental Disorders