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

NCT06150352 | Recruiting DMC

• 1 other identifier: UW 23-291
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Obstructive Sleep Apnea; Mild Cognitive Impairment; Subjective Cognitive Impairment

Keywords

Obstructive sleep apnea; Neurocognitive function; CPAP

Outcome Measures

Primary Outcomes (2)

• Change in neurocognitive function (ADAS Cog)

  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, 2 year, 3 year

• Cerebral amyloid update in moderate to severe OSA and no to mild OSA

  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 Outcomes (8)

• Change in ability to inhibit cognitive interference

  Baseline, 6 months, 1 year, 2 year, 3 year

• Change in neurocognitive function (MoCA)

  Baseline, 6 months, 1 year, 2 year, 3 year

• Change in sleep profile and quality

  Baseline, 6 months, 1 year, 2 year, 3 year

• Change in sleep apnea symptoms

  Baseline, 6 months, 1 year, 2 year, 3 year

• Change in daytime sleepiness

  Baseline, 6 months, 1 year, 2 year, 3 year

Study Arms (1)

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.

Interventions

Continuous Positive Airway Pressure or other management for OSA per clinical indications. DEVICE

PAP therapy or other management will be advised for subjects with OSA per usual clinical criteria

Subjective or mild cognitive impairment patients

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Queen Mary Hospital

Hong Kong, Hong Kong

RECRUITING

Related Publications (8)

• Bao YW, Chau ACM, Chiu PK, Shea YF, Kwan JSK, Chan FHW, Mak HK. Heterogeneity of Amyloid Binding in Cognitively Impaired Patients Consecutively Recruited from a Memory Clinic: Evaluating the Utility of Quantitative 18F-Flutemetamol PET-CT in Discrimination of Mild Cognitive Impairment from Alzheimer's Disease and Other Dementias. J Alzheimers Dis. 2021;79(2):819-832. doi: 10.3233/JAD-200890.

  PMID: 33361593 BACKGROUND

• Collij LE, Mastenbroek SE, Salvado G, Wink AM, Visser PJ, Barkhof F, van Berckel BNM, Lopes Alves I. Regional amyloid accumulation predicts memory decline in initially cognitively unimpaired individuals. Alzheimers Dement (Amst). 2021 Aug 2;13(1):e12216. doi: 10.1002/dad2.12216. eCollection 2021.

  PMID: 34368416 BACKGROUND

• Cui W, Duan Z, Li Z, Feng J. Assessment of Alzheimer's disease-related biomarkers in patients with obstructive sleep apnea: A systematic review and meta-analysis. Front Aging Neurosci. 2022 Oct 13;14:902408. doi: 10.3389/fnagi.2022.902408. eCollection 2022.

  PMID: 36313031 BACKGROUND

• Emamian F, Khazaie H, Tahmasian M, Leschziner GD, Morrell MJ, Hsiung GY, Rosenzweig I, Sepehry AA. The Association Between Obstructive Sleep Apnea and Alzheimer's Disease: A Meta-Analysis Perspective. Front Aging Neurosci. 2016 Apr 12;8:78. doi: 10.3389/fnagi.2016.00078. eCollection 2016.

  PMID: 27148046 BACKGROUND

• Jackson ML, Cavuoto M, Schembri R, Dore V, Villemagne VL, Barnes M, O'Donoghue FJ, Rowe CC, Robinson SR. Severe Obstructive Sleep Apnea Is Associated with Higher Brain Amyloid Burden: A Preliminary PET Imaging Study. J Alzheimers Dis. 2020;78(2):611-617. doi: 10.3233/JAD-200571.

  PMID: 33016907 BACKGROUND

• Leng Y, McEvoy CT, Allen IE, Yaffe K. Association of Sleep-Disordered Breathing With Cognitive Function and Risk of Cognitive Impairment: A Systematic Review and Meta-analysis. JAMA Neurol. 2017 Oct 1;74(10):1237-1245. doi: 10.1001/jamaneurol.2017.2180.

  PMID: 28846764 BACKGROUND

• Lutsey PL, Norby FL, Gottesman RF, Mosley T, MacLehose RF, Punjabi NM, Shahar E, Jack CR Jr, Alonso A. Sleep Apnea, Sleep Duration and Brain MRI Markers of Cerebral Vascular Disease and Alzheimer's Disease: The Atherosclerosis Risk in Communities Study (ARIC). PLoS One. 2016 Jul 14;11(7):e0158758. doi: 10.1371/journal.pone.0158758. eCollection 2016.

  PMID: 27415826 BACKGROUND

• Buckley CJ, Sherwin PF, Smith AP, Wolber J, Weick SM, Brooks DJ. Validation of an electronic image reader training programme for interpretation of [18F]flutemetamol beta-amyloid PET brain images. Nucl Med Commun. 2017 Mar;38(3):234-241. doi: 10.1097/MNM.0000000000000633.

  PMID: 27984539 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood for apolipoprotein E status

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Cognitive Dysfunction

Interventions

Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Study Officials

• Mary SM Ip, MD

  School of Clinical Medicine, The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sau Man Mary Ip, MD

CONTACT

2255 5885; msmip@hku.hk

Yuen Kwan Agnes Lai, PhD

CONTACT

ayklai@hkmu.edu.hk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Emeritus Professor

Study Record Dates

• First Submitted: October 12, 2023
• First Posted: November 29, 2023
• Study Start: September 26, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 2, 2025

Record last verified: 2025-03

Locations

HK (1)