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. Identifier: NCT01482351
Recruitment Status : Completed
First Posted : November 30, 2011
Last Update Posted : March 17, 2015
National Institute on Aging (NIA)
University of Pennsylvania
Information provided by (Responsible Party):
Kathy C. Richards, George Mason University

Brief Summary:
The goal of the research is to determine the power and the feasibility of the study design and methods to inform a full-scale clinical trial that will determine whether treatment of obstructive sleep apnea in older adults with mild cognitive impairment delays cognitive decline and preserves everyday function.

Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnea Mild Cognitive Impairment Device: Continuous Positive Airway Pressure [CPAP] Phase 3

Detailed Description:
We will collect pilot data from 110 participants on 1-year outcomes of treatment of obstructive sleep apnea using continuous positive airway pressure and the validity of neuroimaging for measuring clinical change in persons with mild cognitive impairment and obstructive sleep apnea. The results will inform the study design, sample size, participant recruitment and retention methods, and measures for a full-scale trial.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 participants
Intervention Model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Official Title: Mild Cognitive Impairment and Obstructive Sleep Apnea
Study Start Date : February 2012
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory Sleep Apnea

Arm Intervention/treatment
Experimental: Continuous Positive Airway Pressure
Participants diagnosed with OSA who choose to treat their apnea with Continuous Positive Airway Pressure (CPAP) will be compared with those who do not choose to use CPAP and no-apnea controls at 1 year to assess changes in mild cognitive impairment.
Device: Continuous Positive Airway Pressure [CPAP]
Study participants with sleep apnea will choose to use or not use a continuous positive airway pressure (CPAP) machine to treat their apnea after a consultation with their doctor. Dosage of CPAP will be individually determined using standardized methods in an overnight CPAP titration polysomnography.

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. We will use 6 alternative forms. Forms 1, 2, and 4 will be used for half the participants and forms 3, 5 and 6 will be used for the rest of the participants.

  2. Everyday Cognition [E-Cog] [ Time Frame: Change from baseline at 6 months and 1 year ]
    Cognitively mediated functional abilities will be assessed using E-Cog. It is a study-partner rated 39-item questionnaire.

Secondary Outcome Measures :
  1. Digit Symbol-Coding [DSC] [ Time Frame: Change from baseline at 6 months and 1 year ]
    Psychomotor/cognitive processing speed will be assessed using the DSC subtest from the Wechsler Adult Intelligence Test (WAIS-III).

  2. Mini Mental State 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. It takes about 5 minutes to complete.

  3. Stroop Color and Word Test [SCW] [ Time Frame: Change from baseline at 6 months and 1 year ]
    Attention will be measured using SCW. We will use the Golden format, which is sensitive to age-related declines in processing speed. The SCW has been used in elders with Alzheimer's Disease and it takes about 30 minutes to complete.

  4. The Psychomotor Vigilance Task (PVT) [ Time Frame: Change from baseline at 6 months and 1 year ]
    Attention/reaction time will assessed using the PVT. PVT has been used in elders with Alzheimer's Disease and requires about 30 minutes to complete.

  5. 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. Persons with cognitive impairment are able to complete the scale. It requires 5 minutes to complete.

  6. 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.

  7. 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 can be completed at home by participants or their study partners. It is sensitive to small differences in several domains that may add up to a clinically meaningful change.

  8. Clinical Dementia Rating Scale [CDR] [ Time Frame: Change from baseline at 1 year ]
    Cognitive ability will be assessed and staged using CDR. It uses a structured interview takes 60-90 minutes to complete. The CDR will be completed by the graduate assistant with input from the geriatrician and neuropsychologist.

  9. Neuroimaging Biomarker: Hippocampal Volume [ Time Frame: Change in hippocampal volume between baseline and 1 year follow-up magnetic resonance imaging scan. ]
    Change in hippocampal volume between baseline and 1 year follow-up scan (atrophy) will be quantified automatically using unbiased registration between 2 time points. Structural and calibration scans used in this protocol have been adopted from the Alzheimer's Disease Neuroimaging Initiative [ADNI] protocol.

  10. Neuroimaging Biomarker: Regional Brain Volume and Thickness. [ Time Frame: Change in regional brain volume and thickness between baseline and 1 year follow-up magnetic resonance imaging scan. ]
    Structural effects of CPAP outside of the hippocampus will be measured using FreeSurfer software to automatically estimate hemispheric and lobar cortical thickness; cortical and subcortical gray matter volume; white matter volume; and ventricular volume. The FreeSurfer longitudinal module will be used to estimate change in these measures.

  11. Neuroimaging Biomarker: Hippocampal Subfield Volumes. [ Time Frame: Change in hippocampal subfield volume between baseline and 1 year follow-up magnetic resonance imaging scan ]
    We will perform automatic segmentation of hippocampal subfields in the baseline T2-weighted turbo spin echo [TSE] images. This will estimate volumes of subfields CA1, CA2, CA3, dentate gyrus, subiculum, and entorhinal cortex. We will then quantify longitudinal change in subfield volumes using the approach for the whole hippocampus, modified to account for anisotropic voxel size in TSE images.

  12. Neuroimaging Biomarker: Ischemic Lesion Volume. [ Time Frame: Change in ischemic lesion volume between baseline and 1 year follow-up magnetic resonance imaging scan ]
    The volume of white matter hyperintensity (leuokoaraiosis) will be assessed in CSFsuppressed T2-weighted (FLAIR) structural MRI. A semi-automated intensity-based segmentation technique will be used to identify cortical and subcortical strokes as well as ischemic lesions in subcortical white matter considered to be the sequelae of hypoperfusion.

  13. Neuroimaging Biomarker: Cerebral Blood Flow. [ Time Frame: Change in cerebral blood flow between baseline and 1 year follow-up magnetic resonance imaging scan ]
    ASL perfusion MRI provides regional cerebral blood flow (rCBF) in absolute units of ml/100g/min. Arterial Spin Labeling [ASL] signal processing will follow established procedures in our laboratory using the ASL data processing toolbox (ASL tbx). CBF will then be quantified within cortical gray matter, hippocampal gray matter, and white matter regions based on FreeSurfer templates.

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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

Inclusion Criteria

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

  • Are able to provide written informed consent by self or legally authorized representative. MacArthur Competency Assessment Tool [MacCAT-CR] will be used to assess decision making capacity
  • Moderate to severe obstructive sleep apnea (OSA) as defined by an apnea-hypopnea index (AHI) >= 15 using either the Apnea Risk Evaluation System (ARES) OR diagnostic polysomnography as a screening measure
  • Scoring < = 11 on Dementia Severity Rating Scale
  • Scoring education-adjusted total scores < 26 on Montreal Cognitive Assessment
  • Scoring education adjusted scores 28-35 (inclusive) on Telephone Interview for Cognitive Status Modified
  • Permitted medications stable for at least 4 weeks
  • Scoring less than or equal to14 on the Beck Depression Inventory II (BDI-II) 21-item scale (i.e., non-depressed)
  • Having a study partner, defined as an informant/caregiver who has an average of 10 hours per week or more contact with and accompanies participant to most study visits
  • Adequate visual and auditory acuity to allow testing
  • Women must be surgically sterile, 2 years postmenopausal
  • Testability - willing and able to complete baseline, 6-month, and 1-year outcome measures, and willing to send in the CPAP Smartcard for adherence
  • Willing to undergo magnetic resonance imaging (MRI) and provide DNA for ApoE4 assessments
  • Completed at least 6 grades of education or had a good work history inside or outside the home (to exclude mental retardation)
  • Fluent in English.

Exclusion criteria:

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

  • Any significant neurologic disease other than MCI, such as Parkinson's Disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defects or known structural brain abnormalities
  • Any MRI exclusions - presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin, or body
  • Psychiatric disorders, including major depression or bipolar disorder based on DSM-IV diagnostic criteria within the past 3 months, psychotic features, agitation or behavioral problems within the last 3 months that could lead to difficulty complying with the protocol, or history of schizophrenia (also by DSM-IV criteria)
  • History of alcohol abuse or dependence within the past 2 years (DSM-IV criteria)
  • Any current significant systemic illness or unstable medical condition that could lead to difficulty in complying with the protocol (bronchospasm or symptomatic chronic obstructive pulmonary disease as indicated by regular use of bronchodilators, steroids, history of carbon dioxide retention, waking hypoxemia, or use of supplemental oxygen; uncontrolled thyroid disease, diabetes, or seizure disorder; cirrhosis; recently diagnosed cancer; clinically significant laboratory abnormalities such as B12)
  • Any current known conditions that may increase short-term risk from untreated OSA: symptomatic coronary or cerebrovascular disease as indicated by recent myocardial infarction or stroke (6 months), congestive heart failure (New York Heart Classification stage 3), unstable angina, life-threatening arrhythmias, cardiomyopathy, transient ischemic attacks and history of driving accidents related to daytime sleepiness
  • Participating in clinical studies involving neuropsychological measures being conducted more than twice a year or another clinical trial
  • Currently receiving CPAP or bi-level pressure for OSA; and
  • Requires oxygen or bi-level pressure during CPAP titration polysomnography

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 identifier (NCT number): NCT01482351

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

Responsible Party: Kathy C. Richards, University Professor, George Mason University Identifier: NCT01482351     History of Changes
Other Study ID Numbers: 7584
R01AG034682-01A2 ( U.S. NIH Grant/Contract )
First Posted: November 30, 2011    Key Record Dates
Last Update Posted: March 17, 2015
Last Verified: March 2015

Keywords provided by Kathy C. Richards, George Mason University:
amnestic mild cognitive impairment
older adults
Alzheimer's Disease

Additional relevant MeSH terms:
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Cognitive Dysfunction
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Nervous System Diseases
Cognition Disorders
Neurocognitive Disorders
Mental Disorders