Mild Cognitive Impairment, Obstructive Sleep Apnea
Conditions
Keywords
apnea, cognition, memory, function, amnestic mild cognitive impairment, older adults, Alzheimer's Disease
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.
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.
Interventions
BEHAVIORALCPAP 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.
BEHAVIORALAttention 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.
Sponsors
National Institute on Aging (NIA)
University of Pennsylvania
George Mason University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Persons collecting and analyzing neurocognitive data were blinded to participants' CPAP adherence.
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.
Eligibility
Sex/Gender
ALL
Age
55 Years to 89 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Epworth Sleepiness Scale [ESS] | 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). |
| Digit Symbol Subtest (DS) | 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. |
| Mini Mental State Evaluation Exam (MMSE) | 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). |
| Stroop Color and Word Test (SCW) | 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 wordsredblue 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. |
| The Psychomotor Vigilance Task (PVT) | 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). |
| Hopkins Verbal Learning Test-Revised (HVLT-R) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Everyday Function Outcome: Everyday Cognition (E-Cog) | 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. |
| Alzheimer's Disease Cooperative Study - Clinicians' Global Impression of Change Scale (ADCS-CGIC) | 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. |
| Clinical Dementia Rating Scale (CDR) | 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. |
| Functional Outcomes Sleep Questionnaire (FOSQ) | 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. |
Countries
United States
Participant flow
Recruitment details
From 9/2012 to 12/2014, study investigators identified potential participants from clinical practices, advertisements in newspapers, clinical trials registries, senior centers, advertisements in public transportation centers, the Alzheimer's Association, and support groups.
Participants by arm
| Arm | Count |
|---|---|
| MCI/OSA/CPAP Adherent Device: Continuous Positive Airway Pressure \[CPAP\]. 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 equal to or greater than 4 hours per night over one year.
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. | 29 |
| MCI/OSA/CPAP Non-adherent Device: Continuous Positive Airway Pressure \[CPAP\]. 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 less than 4 hours per night over one year.
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. | 25 |
| Total | 54 |
Baseline characteristics
| Characteristic | MCI/OSA/CPAP Non-adherent | Total | MCI/OSA/CPAP Adherent |
|---|---|---|---|
| Age, Continuous | 73.2 years STANDARD_DEVIATION 8.6 | 70.1 years STANDARD_DEVIATION 8.3 | 67.4 years STANDARD_DEVIATION 7.2 |
| ApoE-E2/E3 | 0 Participants | 1 Participants | 1 Participants |
| ApoE-E2/E4 | 0 Participants | 1 Participants | 1 Participants |
| ApoE-E3/E3 | 18 Participants | 34 Participants | 16 Participants |
| ApoE-E3/E4 | 4 Participants | 13 Participants | 9 Participants |
| ApoE-E4/E4 | 2 Participants | 2 Participants | 0 Participants |
| Apolipoprotein E (ApoE)-E2/E2 | 1 Participants | 1 Participants | 0 Participants |
| ARES - Apnea-Hypopnea Index | 14.6 events/hour STANDARD_DEVIATION 2.7 | 17.1 events/hour STANDARD_DEVIATION 5.8 | 21.3 events/hour STANDARD_DEVIATION 7.8 |
| ARES - Lowest oxygen saturation | 82.9 percentage of blood oxygen saturation STANDARD_DEVIATION 2.8 | 83.1 percentage of blood oxygen saturation STANDARD_DEVIATION 3.1 | 83.6 percentage of blood oxygen saturation STANDARD_DEVIATION 4.3 |
| ARES - Total sleep time | 334.2 minutes STANDARD_DEVIATION 35.6 | 374.3 minutes STANDARD_DEVIATION 84 | 441.0 minutes STANDARD_DEVIATION 107 |
| BDI-II | 6.4 units on a scale STANDARD_DEVIATION 6.6 | 7.1 units on a scale STANDARD_DEVIATION 5.6 | 7.7 units on a scale STANDARD_DEVIATION 4.6 |
| BMI | 29.5 kg/m^2 STANDARD_DEVIATION 6.5 | 29.9 kg/m^2 STANDARD_DEVIATION 6.6 | 30.3 kg/m^2 STANDARD_DEVIATION 6.7 |
| CDR | 0.7 units on a scale STANDARD_DEVIATION 0.7 | 0.6 units on a scale STANDARD_DEVIATION 0.5 | 0.5 units on a scale STANDARD_DEVIATION 0.3 |
| Education | 21 participants | 47 participants | 26 participants |
| ESS | 9.3 units on a scale STANDARD_DEVIATION 5.3 | 8.9 units on a scale STANDARD_DEVIATION 4.4 | 8.5 units on a scale STANDARD_DEVIATION 3.5 |
| Income - >$100,000 | 4 Participants | 16 Participants | 12 Participants |
| Income - <$20,000 | 9 Participants | 12 Participants | 3 Participants |
| Income - $20,000 - $39,999 | 2 Participants | 4 Participants | 2 Participants |
| Income - $40,000 - $69,999 | 4 Participants | 7 Participants | 3 Participants |
| Income - $70,000 - $99,999 | 2 Participants | 6 Participants | 4 Participants |
| Married/Cohabitate | 8 participants | 31 participants | 23 participants |
| Medications-Antidepressants | 1 Participants | 7 Participants | 6 Participants |
| Medications-Antihypertensives | 21 Participants | 40 Participants | 19 Participants |
| Medications-Cholesterol medications | 18 Participants | 39 Participants | 21 Participants |
| Medications-Cholinesterase inhibitors | 2 Participants | 3 Participants | 1 Participants |
| Medications-NMDA Receptor Antagonist | 0 Participants | 0 Participants | 0 Participants |
| Medications-Opioid Analgesics | 3 Participants | 3 Participants | 0 Participants |
| Medications-Sedatives/anxiolytics | 5 Participants | 10 Participants | 5 Participants |
| MMSE | 28.0 units on a scale STANDARD_DEVIATION 2.1 | 28.2 units on a scale STANDARD_DEVIATION 1.7 | 28.3 units on a scale STANDARD_DEVIATION 1.4 |
| PSG - Apnea-Hypopnea Index | 31.1 events/hour STANDARD_DEVIATION 20.8 | 27.2 events/hour STANDARD_DEVIATION 15 | 25.3 events/hour STANDARD_DEVIATION 11.5 |
| PSG - Lowest oxygen saturation | 81.8 percentage of blood oxygen saturation STANDARD_DEVIATION 5 | 82.2 percentage of blood oxygen saturation STANDARD_DEVIATION 6.3 | 82.3 percentage of blood oxygen saturation STANDARD_DEVIATION 6.9 |
| PSG - Total sleep time | 270.5 minutes STANDARD_DEVIATION 95.9 | 279.0 minutes STANDARD_DEVIATION 86.7 | 283.2 minutes STANDARD_DEVIATION 84 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 17 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 35 Participants | 24 Participants |
| Region of Enrollment United States | 25 participants | 54 participants | 29 participants |
| Reported/known conditions-Cardiovascular Disease | 14 Participants | 25 Participants | 11 Participants |
| Reported/known conditions-Diabetes | 8 Participants | 15 Participants | 7 Participants |
| Reported/known conditions-Hypertension | 14 Participants | 29 Participants | 15 Participants |
| Sex: Female, Male Female | 15 Participants | 24 Participants | 9 Participants |
| Sex: Female, Male Male | 10 Participants | 30 Participants | 20 Participants |
| Split-night PSG - Apnea-Hypopnea index | 14.6 events/hour STANDARD_DEVIATION 7.8 | 17.7 events/hour STANDARD_DEVIATION 9.4 | 25.6 events/hour STANDARD_DEVIATION 9.2 |
| Split-night PSG - Lowest oxygen saturation | 82.9 percentage of blood oxygen saturation STANDARD_DEVIATION 6.3 | 83.8 percentage of blood oxygen saturation STANDARD_DEVIATION 6 | 86.0 percentage of blood oxygen saturation STANDARD_DEVIATION 5 |
| Split-night PSG - Total sleep time | 150.4 minutes STANDARD_DEVIATION 77.4 | 166.1 minutes STANDARD_DEVIATION 95.7 | 218.2 minutes STANDARD_DEVIATION 150.6 |
| Study Partner-Adult child | 6 Participants | 7 Participants | 1 Participants |
| Study Partner-Other | 10 Participants | 12 Participants | 2 Participants |
| Study Partner-Spouse/cohabitate | 9 Participants | 35 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 25 |
| other Total, other adverse events | 0 / 29 | 0 / 25 |
| serious Total, serious adverse events | 5 / 29 | 0 / 25 |
Outcome results
Primary
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.
Time frame: Change from baseline at 6 months and 1 year
Population: 14 participants lost to follow-up prior to 6-months testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI/OSA/CPAP Adherent | Digit Symbol Subtest (DS) | 6-months | 9.90 score on a scale | Standard Deviation 2.74 |
| MCI/OSA/CPAP Adherent | Digit Symbol Subtest (DS) | Baseline | 9.18 score on a scale | Standard Deviation 2.59 |
| MCI/OSA/CPAP Adherent | Digit Symbol Subtest (DS) | 1 year | 10.21 score on a scale | Standard Deviation 3.03 |
| MCI/OSA/CPAP Non-adherent | Digit Symbol Subtest (DS) | Baseline | 8.06 score on a scale | Standard Deviation 2.65 |
| MCI/OSA/CPAP Non-adherent | Digit Symbol Subtest (DS) | 6-months | 8.02 score on a scale | Standard Deviation 2.36 |
| MCI/OSA/CPAP Non-adherent | Digit Symbol Subtest (DS) | 1 year | 8.09 score on a scale | Standard Deviation 2.78 |
Primary
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).
Time frame: Change from baseline at 6 months and 1 year
Population: 14 participants were lost to follow-up prior to 6-months testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI/OSA/CPAP Adherent | Epworth Sleepiness Scale [ESS] | Baseline | 8.50 score on a scale | Standard Deviation 3.52 |
| MCI/OSA/CPAP Adherent | Epworth Sleepiness Scale [ESS] | 6-months | 6.54 score on a scale | Standard Deviation 3.17 |
| MCI/OSA/CPAP Adherent | Epworth Sleepiness Scale [ESS] | 1-year | 6.34 score on a scale | Standard Deviation 3.71 |
| MCI/OSA/CPAP Non-adherent | Epworth Sleepiness Scale [ESS] | Baseline | 9.32 score on a scale | Standard Deviation 5.34 |
| MCI/OSA/CPAP Non-adherent | Epworth Sleepiness Scale [ESS] | 6-months | 8.00 score on a scale | Standard Deviation 5.53 |
| MCI/OSA/CPAP Non-adherent | Epworth Sleepiness Scale [ESS] | 1-year | 7.57 score on a scale | Standard Deviation 4.37 |
Primary
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).
Time frame: Change from baseline at 6 months and 1 year
Population: 14 participants lost to follow-up prior to 6-months testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI/OSA/CPAP Adherent | Hopkins Verbal Learning Test-Revised (HVLT-R) | Baseline | 23.52 score on a scale | Standard Deviation 5.56 |
| MCI/OSA/CPAP Adherent | Hopkins Verbal Learning Test-Revised (HVLT-R) | 6-month | 23.68 score on a scale | Standard Deviation 5.08 |
| MCI/OSA/CPAP Adherent | Hopkins Verbal Learning Test-Revised (HVLT-R) | 1 year | 23.59 score on a scale | Standard Deviation 5.73 |
| MCI/OSA/CPAP Non-adherent | Hopkins Verbal Learning Test-Revised (HVLT-R) | Baseline | 20.04 score on a scale | Standard Deviation 5.3 |
| MCI/OSA/CPAP Non-adherent | Hopkins Verbal Learning Test-Revised (HVLT-R) | 6-month | 20.39 score on a scale | Standard Deviation 5.48 |
| MCI/OSA/CPAP Non-adherent | Hopkins Verbal Learning Test-Revised (HVLT-R) | 1 year | 20.82 score on a scale | Standard Deviation 5.69 |
Primary
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).
Time frame: Change from baseline at 6 months and 1 year
Population: 14 participants lost to follow-up prior to 6-months testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI/OSA/CPAP Adherent | Mini Mental State Evaluation Exam (MMSE) | Baseline | 28.34 score on a scale | Standard Deviation 1.4 |
| MCI/OSA/CPAP Adherent | Mini Mental State Evaluation Exam (MMSE) | 6-month | 28.61 score on a scale | Standard Deviation 1.62 |
| MCI/OSA/CPAP Adherent | Mini Mental State Evaluation Exam (MMSE) | 1-year | 27.93 score on a scale | Standard Deviation 2.05 |
| MCI/OSA/CPAP Non-adherent | Mini Mental State Evaluation Exam (MMSE) | Baseline | 28.00 score on a scale | Standard Deviation 2.1 |
| MCI/OSA/CPAP Non-adherent | Mini Mental State Evaluation Exam (MMSE) | 6-month | 27.48 score on a scale | Standard Deviation 2 |
| MCI/OSA/CPAP Non-adherent | Mini Mental State Evaluation Exam (MMSE) | 1-year | 26.43 score on a scale | Standard Deviation 2.46 |
Primary
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 wordsredblue 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.
Time frame: Change from baseline at 6 months and 1 year
Population: 14 participants were lost to follow-up prior to 6-months testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI/OSA/CPAP Adherent | Stroop Color and Word Test (SCW) | Baseline | 47.36 score on a scale | Standard Deviation 6.15 |
| MCI/OSA/CPAP Adherent | Stroop Color and Word Test (SCW) | 6-month | 48.22 score on a scale | Standard Deviation 8.2 |
| MCI/OSA/CPAP Adherent | Stroop Color and Word Test (SCW) | 1-year | 50.00 score on a scale | Standard Deviation 7.4 |
| MCI/OSA/CPAP Non-adherent | Stroop Color and Word Test (SCW) | Baseline | 44.28 score on a scale | Standard Deviation 8.19 |
| MCI/OSA/CPAP Non-adherent | Stroop Color and Word Test (SCW) | 6-month | 45.36 score on a scale | Standard Deviation 8.57 |
| MCI/OSA/CPAP Non-adherent | Stroop Color and Word Test (SCW) | 1-year | 45.14 score on a scale | Standard Deviation 9.47 |
Primary
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).
Time frame: Change from baseline at 6 months and 1 year
Population: 14 participants were lost to follow-up prior to 6-months testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI/OSA/CPAP Adherent | The Psychomotor Vigilance Task (PVT) | Baseline | 3.09 score on a scale | Standard Deviation 1.53 |
| MCI/OSA/CPAP Adherent | The Psychomotor Vigilance Task (PVT) | 6-month | 2.58 score on a scale | Standard Deviation 1.64 |
| MCI/OSA/CPAP Adherent | The Psychomotor Vigilance Task (PVT) | 1-year | 2.77 score on a scale | Standard Deviation 1.91 |
| MCI/OSA/CPAP Non-adherent | The Psychomotor Vigilance Task (PVT) | Baseline | 6.46 score on a scale | Standard Deviation 3.66 |
| MCI/OSA/CPAP Non-adherent | The Psychomotor Vigilance Task (PVT) | 6-month | 4.29 score on a scale | Standard Deviation 2.71 |
| MCI/OSA/CPAP Non-adherent | The Psychomotor Vigilance Task (PVT) | 1-year | 4.76 score on a scale | Standard Deviation 2.94 |
Secondary
Alzheimer's Disease Cooperative Study - Clinicians' Global Impression of Change Scale (ADCS-CGIC)
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.
Time frame: Change from baseline at 1 year
Population: Participants who completed the study and improved on ADCS-CGIC scores at 1year adjusted for age, race and marital status.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI/OSA/CPAP Adherent | Alzheimer's Disease Cooperative Study - Clinicians' Global Impression of Change Scale (ADCS-CGIC) | ADCS-CGIC Improved | 34 participants |
| MCI/OSA/CPAP Adherent | Alzheimer's Disease Cooperative Study - Clinicians' Global Impression of Change Scale (ADCS-CGIC) | ADCS-CGIC Unimproved | 7 participants |
Secondary
Clinical Dementia Rating Scale (CDR)
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.
Time frame: Change from baseline at 1 year
Population: Study participants who completed the study and improved on CDR data adjusted for age, race and marital status.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI/OSA/CPAP Adherent | Clinical Dementia Rating Scale (CDR) | CDR Improved | 21 participants |
| MCI/OSA/CPAP Adherent | Clinical Dementia Rating Scale (CDR) | CDR Unimproved | 21 participants |
Secondary
Everyday Function Outcome: Everyday Cognition (E-Cog)
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.
Time frame: Change from baseline at 6 months and 1 year
Population: 14 participants were lost to follow up prior to 6 months testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI/OSA/CPAP Adherent | Everyday Function Outcome: Everyday Cognition (E-Cog) | Baseline | 1.46 score on a scale | Standard Deviation 0.54 |
| MCI/OSA/CPAP Adherent | Everyday Function Outcome: Everyday Cognition (E-Cog) | 6 months | 1.35 score on a scale | Standard Deviation 0.36 |
| MCI/OSA/CPAP Adherent | Everyday Function Outcome: Everyday Cognition (E-Cog) | 1-year | 1.35 score on a scale | Standard Deviation 0.51 |
| MCI/OSA/CPAP Non-adherent | Everyday Function Outcome: Everyday Cognition (E-Cog) | Baseline | 1.29 score on a scale | Standard Deviation 0.41 |
| MCI/OSA/CPAP Non-adherent | Everyday Function Outcome: Everyday Cognition (E-Cog) | 6 months | 1.43 score on a scale | Standard Deviation 0.52 |
| MCI/OSA/CPAP Non-adherent | Everyday Function Outcome: Everyday Cognition (E-Cog) | 1-year | 1.52 score on a scale | Standard Deviation 0.7 |
Secondary
Functional Outcomes Sleep Questionnaire (FOSQ)
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.
Time frame: Change from baseline at 6 months and 1 year
Population: 14 participants were lost to follow-up prior to 6-months testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI/OSA/CPAP Adherent | Functional Outcomes Sleep Questionnaire (FOSQ) | Baseline | 17.31 score on a scale | Standard Deviation 1.99 |
| MCI/OSA/CPAP Adherent | Functional Outcomes Sleep Questionnaire (FOSQ) | 6-month | 18.17 score on a scale | Standard Deviation 1.48 |
| MCI/OSA/CPAP Adherent | Functional Outcomes Sleep Questionnaire (FOSQ) | 1-year | 18.30 score on a scale | Standard Deviation 1.82 |
| MCI/OSA/CPAP Non-adherent | Functional Outcomes Sleep Questionnaire (FOSQ) | Baseline | 17.34 score on a scale | Standard Deviation 2.66 |
| MCI/OSA/CPAP Non-adherent | Functional Outcomes Sleep Questionnaire (FOSQ) | 6-month | 18.13 score on a scale | Standard Deviation 2.14 |
| MCI/OSA/CPAP Non-adherent | Functional Outcomes Sleep Questionnaire (FOSQ) | 1-year | 18.63 score on a scale | Standard Deviation 1.95 |