MCI: CPAP Treatment of OSA (Memories2) (MCI:OSA)

Changing the Trajectory of Mild Cognitive Impairment With CPAP Treatment of Obstructive Sleep Apnea

The purpose of this project is to determine whether obstructive sleep apnea (OSA) treatment with positive airway pressure therapy (CPAP) can delay the progression of cognitive impairment in patients with amnestic Mild Cognitive Impairment (MCI) as measured by cognitive testing, and brain magnetic resonance imaging (MRI) scans. Study participants will be assessed at baseline, six-month (cognitive tests only) and one-year follow-up.

Study Overview

• Status: Active, not recruiting
• Conditions: Sleep Apnea, Obstructive; Mild Cognitive Impairment
• Intervention / Treatment: Device: CPAP

Detailed Description

A growing number of research studies suggest that obstructive sleep apnea (OSA), characterized by episodic nocturnal collapse of the upper airway and reduction/cessation of breathing leading to significant nocturnal hypoxia, is associated with an increased risk of cognitive impairment. OSA is effectively treated with continuous positive airway pressure (CPAP), a pressurized nasal/face mask worn during sleep, but health care providers do not often prescribe it for Mild Cognitive Impairment (MCI) because there are no large, prospective research studies in this population confirming efficacy.

This multi-site study will have a sample size of n=460 divided into three groups followed for one year: 1) a CPAP adherent group (approximately n=200); 2) two control groups consisting of 2a) a CPAP non-adherent control group (approximately n=160) and 2b) a no apnea control group (n=100). This will allow us to confirm whether CPAP treatment, controlling for risk factors such as neuroimaging findings and OSA severity at baseline, predicts the primary outcome of cognitive function at 1-year follow-up. Study participants will also undergo an Amyloid PET scan, use wearable activity monitors and functional/structural MRI brain scans.

This research study will thus examine the one year effects of CPAP on cognitive function and elucidate physiological mechanisms for cognitive decline in aMCI and OSA.

• Study Type: Interventional
• Enrollment (Actual): 327
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63130-4862
      • Washington University in St. Louis
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Austin, Texas, United States, 78701
      • University of Texas at Austin
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. age 55-85 years;
2. moderate to severe OSA as defined by an AHI ≥ 15 events/hr, or no apnea defined by an AHI<5 events/hr using American Academy of Sleep Medicine (AASM) diagnostic methodology as determined on a diagnostic polysomnography;
3. Scoring education adjusted scores 28-35 (inclusive) on optional Telephone Interview for Cognitive Status Modified (pre-screen);
4. Scoring 0-0.5 on the Clinical Dementia Rating Scale (CDR);
5. Scoring 23-30 on the Mini Mental State Examination (MMSE) (exceptions may be made for participants with <8 years of education as determined by the clinical research team);
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 a test from the Wechsler memory scale;
7. permitted medications (antidepressants, etc.) stable for at least 4 weeks (12 weeks for cholinesterase inhibitors/memantine) as per ADNI3 criteria;
8. Non-depressed: Scoring < 6 on the Geriatric Depression Scale;
9. study partner, defined as an informant/caregiver who will be able to answer questions about the study participant, and meets one of the following criteria: (a) lives with the participant; (b) spends at least 3 times per week in-person contact with the participant; (c) spends at least 3 times per week in phone contact with the participant; or (d) spends at least 10 hours per week in any combination of phone or in person contact;
10. adequate visual and auditory acuity to allow testing;
11. Post-menopause or surgically sterile;
12. testability - willing and able to complete baseline, 6-month, and 1-year outcome measures, and willing to send in the CPAP Smartcard for adherence;
13. completed at least 6 grades of education; and
14. fluent in English or Spanish.

Exclusion Criteria:

1. any significant neurologic disease other than aMCI, such as Parkinson's Disease, Huntington's disease, normal pressure hydrocephalus, progressive supranuclear palsy, multiple sclerosis, head trauma followed by permanent neurologic deficits or known congenital brain structure abnormalities; within the past 6 months brain tumor, or seizure disorder, or subdural hematoma, or post-stroke (based on Modified Hachinski Ischemic Score);
2. Optional: MRI exclusions - presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin, or body; however, the participant has the option of participating in the study without having an MRI;
3. psychiatric disorders, including uncontrolled major depression, newly diagnosed or exacerbation in past 6 months of bipolar disorder as described in the DSM-IV, psychotic features, agitation or behavioral problems within the past 6 months that could lead to difficulty complying with the protocol, or history of schizophrenia (DSM-IV criteria);
4. history of alcohol abuse or dependence within the past 6 months (DSM-IV criteria);
5. any current significant systemic illness or unstable medical condition that could lead to difficulty in complying with the protocol (such as unstable cardiovascular disease); current use of supplemental oxygen or hypoxemia indicated by documented daytime oxyhemoglobin saturation <90% on room air, uncontrolled thyroid disease (to be included must be on stable dose of thyroid medication for >6 months), uncontrolled cirrhosis, cancer diagnosis within the past 6 months (exceptions may be made at the PI's discretion depending on cancer severity and the treatment required), clinically significant laboratory abnormalities such as reported untreated folate, B12, or TSH disease, or resident of a skilled nursing facility;
6. participation in clinical studies involving neuropsychological measures being conducted more than twice a year;
7. received and was adherent to CPAP or bi-level pressure for OSA within the past 6 months;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPAP adherent; Study participants in this arm are using the CPAP intervention consistently	Device: CPAP; non-invasive positive airway pressure applied using an oronasal mask; Other Names: continuous positive airway pressure therapy
Active Comparator: CPAP non-adherent; Study participants in this arm are not using the CPAP intervention consistently	Device: CPAP; non-invasive positive airway pressure applied using an oronasal mask; Other Names: continuous positive airway pressure therapy
No Intervention: No OSA; Study participants who do not have OSA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digit Symbol-Coding test	incorporates both elements of memory and processing speed and correlates with executive functioning	one-year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Dementia Rating Scale	Assessment of global cognition	one-year follow-up

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Nalaka Gooneratne, MD, MSc, Associate professor; Principal Investigator: Kathy Richards, PhD, Professor; Principal Investigator: David Wolk, MD, Associate professor

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2018
• Primary Completion (Actual): January 31, 2023
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: April 9, 2017
• First Submitted That Met QC Criteria: April 9, 2017
• First Posted (Actual): April 13, 2017

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: sleep apnea; cognitive impairment; positive airway pressure therapy
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurocognitive Disorders; Signs and Symptoms, Respiratory; Cognition Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Cognitive Dysfunction
• Other Study ID Numbers: PD10057866; R01AG054435 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Pending

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes