Mild Cognitive Impairment and Obstructive Sleep Apnea (MEMORIES)

February 20, 2019 updated by: Kathy C. Richards, George Mason University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Abington Memorial Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Virginia
      • Fairfax, Virginia, United States, 22030
        • George Mason University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Change from baseline at 6 months and 1 year
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.
Change from baseline at 6 months and 1 year
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).
Change from baseline at 6 months and 1 year
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.
Change from baseline at 6 months and 1 year
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).
Change from baseline at 6 months and 1 year
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).
Change from baseline at 6 months and 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Change from baseline at 6 months and 1 year
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.
Change from baseline at 6 months and 1 year
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.
Change from baseline at 1 year
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.
Change from baseline at 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

George Mason University

Collaborators

University of Pennsylvania
National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Kathy Richards, PhD, RN, George Mason University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

November 28, 2011

First Submitted That Met QC Criteria

November 28, 2011

First Posted (Estimate)

November 30, 2011

Study Record Updates

Last Update Posted (Actual)

March 6, 2019

Last Update Submitted That Met QC Criteria

February 20, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 7584
  • R01AG034682-01A2 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Time Frame

Data will be made available 6 months after publication of the main study findings and will be available in perpetuity.

IPD Sharing Access Criteria

Individual participant data (IPD) will be publicly available via the following url

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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