Sleep Apnea, Neurocognitive Decline and Brain Imaging in Patients With Subjective or Mild Cognitive Impairment

November 20, 2023 updated by: Professor Mary Ip Sau-man, The University of Hong Kong

Exploring the Association Between Cognitive Function, Obstructive Sleep Apnea and Brain Imaging, and the Determinants of Neurocognitive Decline in Subjects With Subjective or Mild Cognitive Impairment

Obstructive sleep apnea (OSA) is recurrent episodes of partial or complete obstruction of the upper airway during sleep that causes intermittent hypoxia and sleep fragmentation and potentially lead to cardiometabolic and neurocognitive sequelae. Chronic intermittent hypoxia, sleep fragmentation of OSA, and insufficient sleep have been significantly associated with higher risks of neurocognitive impairment, including mild cognitive impairment (MCI) and Alzheimer's disease. Thus, sleep and sleep apnea might be modifiable factors to neurocognitive impairment.

Positive airway pressure (PAP) is the first line of treatment to maintain open airways for patients with OSA. Improving sleep, sleep apnea and circadian function could be a high-value intervention target to alleviate cognitive impairment and decline in subjects with mild neurocognitive impairment.

Amyloid accumulation in brain tissue is a distinct feature of Alzheimers' disease, which is associated with potential impairment of neurocognition clinically. It predicts memory decline in initially cognitively unimpaired individuals.

The study explores the associations between sleep apnea, cognitive function and cerebral imaging and the role of PAP therapy on neurocognitive trajectory in these patients with subjective cognitive impairment /mild cognitive impairment (SCI/MCI).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Obstructive sleep apnea (OSA) is recurrent episodes of partial or complete obstruction of the upper airway during sleep . Chronic intermittent hypoxia, sleep fragmentation of OSA, and insufficient sleep have been significantly associated with higher risks of neurocognitive impairment, including mild MCI and Alzheimer's disease. Thus, sleep and sleep apnea might be modifiable factors contributing towards neurocognitive impairment . Improving sleep and sleep apnea could be a high-value intervention to alleviate cognitive impairment and decline in subjects with mild neurocognitive impairment.

Amyloid accumulation in brain tissue is a distinct feature of Alzheimer's disease, which is associated with potential impairment of neurocognition clinically. It predicts memory decline in initially cognitively unimpaired individuals. Research suggested that cerebrospinal fluid amyloid-β42 levels showed significant differences in subjects with moderate/severe OSA compared with healthy control.

Investigators hypothesize that (i) OSA is a determinant of neurocognitive decline, and regular PAP therapy for OSA could reduce this decline in subjects presenting with subjective cognitive impairment (SCI) or MCI; (ii) OSA may contribute to cerebral amyloid burden in these subjects with clinical diagnosis of SCI/MCI.

This study (i) assesses the role of obstructive sleep apnea as a potential determinant of neurocognitive status and the impact of OSA therapy (CPAP or other interventions) on neurocognitive decline (ii) evaluates if OSA increases cerebral amyloid deposition using PET imaging.

Subjects are recruited from Memory clinic and who have undergone a study with sleep questionnaires, neurocognitive tests and home sleep apnea test (HSAT). Subjects with OSA (identified on HSAT) will be referred for management of OSA per usual clinical criteria. Sleep questionnaires and cognitive assessment tests will be reassessed at six months and one year, and determinants to neurocognitive changes will be analyzed.

Amyloid PET-MRI brain will also be done at baseline. Owing to resource constraints, investigators can only provide PET-MRI investigation for 90 subjects ( 60 subjects with moderate/severe OSA to be compared with 30 subjects with no OSA) .

Study Type

Observational

Enrollment (Estimated)

180

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Sau Man Mary Ip, MD
  • Phone Number: 2255 4605
  • Email: msmip@hku.hk

Study Contact Backup

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Queen Mary Hospital
        • Contact:
          • Sau Man Mary Ip, MD
          • Phone Number: 2255 4605
          • Email: msmip@hku.hk
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients will be recruit in the Memory clinic or Sleep clinic, Queen Mary Hospital

Description

Inclusion Criteria:

  • Aged 50 - 80 years
  • Diagnosis of mild cognitive impairment based on Peterson's criteria.
  • Diagnosis of subjective cognitive impairment, based on the subjective complaint of cognitive impairment, but with an unremarkable assessment of the Hong Kong version of Montreal cognitive Assessment scores
  • Able to speak and read Chinese
  • Adequate visual and auditory to perform a cognitive test
  • Subjects with moderate-severe OSA or No OSA (diagnosis based on sleep study) would be invited for baseline PET-MRI brain scan

Exclusion Criteria:

  • Diagnosed psychiatric illness with or without medication, e.g. major depressive disorder.
  • Other clear organic causes of cognitive impairment, e.g. vascular cognitive impairment, brain tumour, dementia with Lewy body, mild cognitive impairment with Lewy body, Parkinson's disease, normal pressure hydrocephalus, neurosyphilis, autoimmune encephalitis, substance abuse, history of alcohol abuse.
  • Diagnosis of cancer on active treatment
  • Contraindications to PET-CT or MRI brain scan (excluded for neuroimaging studies)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Subjective or mild cognitive impairment patients
Subjective or mild cognitive impairment patients with or without CPAP treatment
Device: Continuous Positive Airway Pressure or other management for OSA per clinical indications.
PAP therapy or other management will be advised for subjects with OSA per usual clinical criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in neurocognitive function (ADAS Cog)
Time Frame: Baseline, 6 months, 1 year
Measured by ADAS-Cog. The scores range from 0 to 70, "0" is the best possible score and "70" is the worst possible score.
Baseline, 6 months, 1 year
Cerebral amyloid update in moderate to severe OSA and no OSA
Time Frame: Baseline
The brain images for each subject will consist of fused MRI (3D MPRAGE) and 18F-Flutemetamol PET images. The scans were visually interpreted as positive (abnormal) or negative (normal) by a trained neuroradiologist based on uptake of 18F-Flutemetamol.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in ability to inhibit cognitive interference
Time Frame: Baseline, 6 months, 1 year
Measured by Stroop Colour and Word Test (SCWT). Scored by time and error. A longer time indicates a worst score, while a shorter time indicates a better score.
Baseline, 6 months, 1 year
Change in neurocognitive function (MoCA)
Time Frame: Baseline, 6 months, 1 year
Measured by Montreal Cognitive Assessment (MoCA) score. The scores range from 0 to 30, "0" is the worst possible score and "30" is the best possible score.
Baseline, 6 months, 1 year
Change in sleep profile and quality
Time Frame: Baseline, 6 months, 1 year
Measured by Severe Insomnia Index. Each item asks the individual to rate the severity of his or her symptoms with a 4-point Likert scale. The total score ranges from 0 to 28. The higher the scores the greater the severity of insomnia
Baseline, 6 months, 1 year
Change in sleep apnea symptoms
Time Frame: Baseline, 6 months, 1 year
Measured by Pittsburgh Sleep Quality Index. Each of the sleep components yields a score ranging from 0 to 3, with 3 indicating the greatest dysfunction. The sleep component scores are summed to yield a total score ranging from 0 to 21, with the higher total score indicating worse sleep quality.
Baseline, 6 months, 1 year
Change in daytime sleepiness
Time Frame: Baseline, 6 months, 1 year
Measured by Epworth Sleepiness Scale. Each item asks the individual to rate their daytime sleepiness. The total score ranges from 0 to 24. The higher the scores, the greater the severity of daytime sleepiness
Baseline, 6 months, 1 year
Change in insomnia symptoms
Time Frame: Baseline, 6 months, 1 year
Measured by Severe Insomnia Index. Each item asks the individual to rate the severity of his or her symptoms with a 4-point Likert scale. The total score ranges from 0 to 28. The higher the scores, the greater the severity of insomnia
Baseline, 6 months, 1 year
Change in depression symptoms
Time Frame: Baseline, 6 months, 1 year
Measured by Geriatric Depression Scale - short form. The score ranges from 0 to 15. The higher the scores the more severe of depression.
Baseline, 6 months, 1 year
Neuroimaging outcomes between two groups of subjects with moderate-severe OSA or no OSA
Time Frame: Baseline

A. Cerebral amyloid burden as measured by SUVR global and regional scores on 18F-Flutemetamol PET-CT imaging:

Normalized for injected dose and body weight of each subject, standardized uptake values (SUVs) are calculated in 16 Alzheimer's disease signature brain regions by Cortex-ID softward (General Electric Healthcare Ltd., USA). The composite SUVR representing the global amyloid burden is the average SUVR value of the area-weighted mean for the 16 cortical ROIs;

B. Cortical brain volumes based on brain segmentation using 3D T1-MPRAGE images by Freesurfer software, including total, deep gray and hippocampal volumes; temporal, parietal, frontal and occipital cortical volumes; and Alzheimer's signature regional volumes
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Investigators

  • Principal Investigator: Mary SM Ip, MD, School of Clinical Medicine, The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2023

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

March 31, 2027

Study Registration Dates

First Submitted

October 12, 2023

First Submitted That Met QC Criteria

November 20, 2023

First Posted (Actual)

November 29, 2023

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 23-291

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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