Clinical trial NCT01482351: Mild Cognitive Impairment and Obstructive Sleep Apnea
Official title: Mild Cognitive Impairment and Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obstructive Sleep Apnea
Mild Cognitive Impairment
Keywords: apnea
cognition
memory
function
amnestic mild cognitive impairment
older adults
Alzheimer's Disease
Lead sponsor: George Mason University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: University of Pennsylvania
First posted: 2011-11-30
Enrollment: 54
Sex: ALL
Minimum age (years): 55
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Hopkins Verbal Learning Test-Revised (HVLT-R)
timeFrame: Change from baseline at 6 months and 1 year
measure: Digit Symbol Subtest (DS)
timeFrame: Change from baseline at 6 months and 1 year
measure: Mini Mental State Evaluation Exam (MMSE)
timeFrame: Change from baseline at 6 months and 1 year
measure: Stroop Color and Word Test (SCW)
timeFrame: Change from baseline at 6 months and 1 year
measure: The Psychomotor Vigilance Task (PVT)
timeFrame: Change from baseline at 6 months and 1 year
measure: Epworth Sleepiness Scale [ESS]
timeFrame: Change from baseline at 6 months and 1 year
Secondary outcomes:
measure: Functional Outcomes Sleep Questionnaire (FOSQ)
timeFrame: Change from baseline at 6 months and 1 year
measure: Everyday Function Outcome: Everyday Cognition (E-Cog)
timeFrame: Change from baseline at 6 months and 1 year
measure: Alzheimer's Disease Cooperative Study - Clinicians' Global Impression of Change Scale (ADCS-CGIC)
timeFrame: Change from baseline at 1 year
measure: Clinical Dementia Rating Scale (CDR)
timeFrame: Change from baseline at 1 year
Other outcomes:
Locations:
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Fairfax
country: United States
facility: George Mason University
state: Virginia
Study officials:
affiliation: George Mason University
name: Kathy Richards, PhD, RN
role: PRINCIPAL_INVESTIGATOR
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