Mild Cognitive Impairment and Obstructive Sleep Apnea

Obstructive Sleep Apnea Clinical Trial

— MEMORIES  

Official title:

Mild Cognitive Impairment and Obstructive Sleep Apnea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01482351
• Other study ID #: 7584
• Secondary ID: R01AG034682-01A2
• Status: Completed
• Phase: N/A
• Start date: September 2012
• Est. completion date: December 2014

Study information

• Verified date: February 2019
• Source: George Mason University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 89 Years

Eligibility

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.

Related Conditions & MeSH terms

• Apnea
• Cognitive Dysfunction
• Mild Cognitive Impairment
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	George Mason University	Fairfax	Virginia
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
George Mason University	National Institute on Aging (NIA), University of Pennsylvania

Country where clinical trial is conducted

United States, 

References & Publications (20)

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* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	Change from baseline at 6 months and 1 year
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.	Change from baseline at 6 months and 1 year
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).	Change from baseline at 6 months and 1 year
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 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
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).	Change from baseline at 6 months and 1 year
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).	Change from baseline at 6 months and 1 year
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.	Change from baseline at 6 months and 1 year
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.	Change from baseline at 6 months and 1 year
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.	Change from baseline at 1 year
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.	Change from baseline at 1 year