Biomarkers of Dementia in Chronic Sleep and Breathing Disorders

NCT06377332 | Unknown

• 1 other identifier: X23-0330
• Study Type: observational
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic obstructive pulmonary disease (COPD), obstructive sleep apnoea (OSA) and overlap syndrome are associated with obstructions in breathing and disturbed sleep. Chronic breathing disruptions and poor sleep may lead to cognitive impairment and brain changes linked with early neurodegenerative processes. As such, identifying early markers of cognitive impairment and dementia risk in individuals with chronic respiratory and sleep breathing disorders is crucial for understanding how these diseases may contribute to accelerated brain ageing. This study will comprehensively measure sleep, lung function, cognitive performance and blood-based markers of dementia risk and inflammation. The investigators will use innovative technologies to identify biomarkers of cognitive impairment and dementia risk in people with chronic sleep and breathing disorders. The investigators will also investigate the relationships between disrupted sleep and abnormal breathing and the brain. This research may also inform future early interventions to improve cognition and brain health in chronic sleep and respiratory disease.

Conditions

COPD; Overlap Syndrome; OSA

Keywords

Biomarkers; Observational; Cross-Sectional

Outcome Measures

Primary Outcomes (2)

• Scores on the Montreal Cognitive Assessment (MoCA) neuropsychological assessment for dementia risk.

  MoCA scores of 18 to 25 indicate mild cognitive impairment, 10 to 17 indicate moderate cognitive impairment and scores below 10 indicate severe cognitive impairment. Associations between MoCA and night-time hypoxemia / sleep fragmentation in the entire sample.

  Cross-sectional/baseline only

• Blood levels of amyloid beta (Aβ40/Aβ42 ratio).

  Associations between blood levels of Aβ (Aβ40/Aβ42 ratio) and night-time hypoxemia / sleep fragmentation in the entire sample.

  Cross-sectional/baseline only

Secondary Outcomes (24)

• Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep.

  Cross-sectional/baseline only

• Brain tissue oxygenation during cognitive tasks and sleep.

  Cross-sectional/baseline only

• Hypoxemia as measured by pulse oximetry.

  Cross-sectional/baseline only

• Sleep Fragmentation

  Cross-sectional/baseline only

• Assessment of premorbid functioning and preinjury through the Test of Premorbid Functioning (TOPF).

  Cross-sectional/baseline only

Other Outcomes (13)

• Brain structure: cortical thickness and volumetric brain maps

  Cross-sectional/baseline only

• Brain structure: diffusion-weighted imaging

  Cross-sectional/baseline only

• Brain function: resting-state BOLD fMRI

  Cross-sectional/baseline only

Study Arms (4)

Chronic Obstructive Pulmonary Disease (COPD)

Males and females; Aged 40-65 years; COPD confirmed by diagnosis or a positive lung function test (GOLD 2 minimum, FEV1 ≥50%, \< 80% predicted; FEV1/FVC \< 0.7); 10-pack year smoking history; Able to perform neuropsychological and cognitive testing; Fluent in English.

Diagnostic Test: High density electroencephalogram (HdEEG); Diagnostic Test: Functional near infrared spectroscopy (fNIRS); Diagnostic Test: Magnetic resonance imaging (MRI); Biological: Blood collection; Diagnostic Test: Neuropsychological battery; Other: Questionnaires; Diagnostic Test: Pulmonary Function Test (PFT); Other: Cognitive Assessment; Diagnostic Test: Polysomnogram (PSG)

Overlap Syndrome (OVS)

Males and females; Aged 40-65 years; Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) ≥15/hr OR defined by polysomnography (PSG) AHI of ≥ 15 COPD confirmed by diagnosis or a positive lung function test (GOLD 2 minimum, FEV1 ≥50%, \< 80% predicted; FEV1/FVC \< 0.7); 10-pack year smoking history; Able to perform neuropsychological and cognitive testing; Fluent in English.

Diagnostic Test: High density electroencephalogram (HdEEG); Diagnostic Test: Functional near infrared spectroscopy (fNIRS); Diagnostic Test: Magnetic resonance imaging (MRI); Biological: Blood collection; Diagnostic Test: Neuropsychological battery; Other: Questionnaires; Diagnostic Test: Pulmonary Function Test (PFT); Other: Cognitive Assessment; Diagnostic Test: Polysomnogram (PSG)

Obstructive Sleep Apnoea (OSA)

Males and females; Aged 40-65 years; Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) ≥15/hr OR defined by polysomnography (PSG) AHI of ≥ 15. Able to give informed consent; Ability to perform neuropsychological and cognitive testing; Fluent in English.

Diagnostic Test: High density electroencephalogram (HdEEG); Diagnostic Test: Functional near infrared spectroscopy (fNIRS); Diagnostic Test: Magnetic resonance imaging (MRI); Biological: Blood collection; Diagnostic Test: Neuropsychological battery; Other: Questionnaires; Diagnostic Test: Pulmonary Function Test (PFT); Other: Cognitive Assessment; Diagnostic Test: Polysomnogram (PSG)

Control

Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English.

Diagnostic Test: High density electroencephalogram (HdEEG); Diagnostic Test: Functional near infrared spectroscopy (fNIRS); Diagnostic Test: Magnetic resonance imaging (MRI); Biological: Blood collection; Diagnostic Test: Neuropsychological battery; Other: Questionnaires; Diagnostic Test: Pulmonary Function Test (PFT); Other: Cognitive Assessment; Diagnostic Test: Polysomnogram (PSG)

Interventions

High density electroencephalogram (HdEEG) DIAGNOSTIC_TEST

High-density electroencephalography (HdEEG) will be utilised in the investigation of sleep-mediated neuronal functions in controls, OSA, COPD and overlap syndrome and the association with accelerated brain ageing and cognitive impairment.

Chronic Obstructive Pulmonary Disease (COPD); Control; Obstructive Sleep Apnoea (OSA); Overlap Syndrome (OVS)

Functional near infrared spectroscopy (fNIRS) DIAGNOSTIC_TEST

Functional near infrared spectroscopy (fNIRS) is one of the most advanced techniques in measuring brain oxygen content and hemodynamic activity. This information indirectly displays neuronal activity and provides a novel opportunity understand brain oxygenation, neurodegenerative diseases, and cognitive function.

Chronic Obstructive Pulmonary Disease (COPD); Control; Obstructive Sleep Apnoea (OSA); Overlap Syndrome (OVS)

Magnetic resonance imaging (MRI) DIAGNOSTIC_TEST

Magnetic resonance imaging (MRI) will be utilised to assess potential structural neuronal changes associated with neurodegenerative disease in those with COPD, OSA and overlap syndrome. MRI has the capacity to provide vital information regarding neuroimaging standards in cerebral vascular damage such as white matter hyperintensities (WMH), lacunes, cerebral microbleeds, brain atrophy and subcortical infarct. Through the utility of MRI sequences such as T1 and T2 weighted imaging, diffusion weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) and resting-state fMRI (rs-fMRI), the investigators will assess neurodegenerative-related structural brain changes in individuals with COPD, OSA and overlap syndrome and examine the differences between these target groups.

Chronic Obstructive Pulmonary Disease (COPD); Control; Obstructive Sleep Apnoea (OSA); Overlap Syndrome (OVS)

Blood collection BIOLOGICAL

A fasting 50mL blood sample will be collected at the experimental visit in the morning following the overnight sleep study. Blood samples will be processed after collection and stored at -80 degrees for future batch analyses. Analyses will include markers for inflammation and dementia including but not limited to ptau217 and beta amyloid. Routine blood analyses will be conducted on 17.5mL of the sample collected for baseline measures. Routine blood analyses includes lipid profile, glucose studies, insulin, high-sensitivity C-reactive protein (hs-CRP), iron studies, thyroid function, b12/folate, homocysteine, prolactin, calcium, full blood count and biochemistry panel for the OSA, COPD and overlap syndrome groups. Routine blood analyses for controls include glucose studies, lipid profile, hs-CRP and biochemistry panel.

Chronic Obstructive Pulmonary Disease (COPD); Control; Obstructive Sleep Apnoea (OSA); Overlap Syndrome (OVS)

Neuropsychological battery DIAGNOSTIC_TEST

A. Montreal Cognitive Assessment (MoCA): B. Test of Premorbid Functioning (TOPF): C. Rey Auditory Verbal Learning Test (RAVLT): D. D-KEFS Colour Word Interference Test (D-CWIT): E. Trail Making Test (TMT): F. Symbol Digit Modalities Test (SDMT) - Oral Version: G. RAVLT 20-minute recall H. Controlled Oral Word Association Test (COWAT):

Chronic Obstructive Pulmonary Disease (COPD); Control; Obstructive Sleep Apnoea (OSA); Overlap Syndrome (OVS)

Questionnaires OTHER

1. Epworth Sleepiness Scale (ESS) 2. PROMIS sleep questionnaire 8a, 3. PROMIS sleep questionnaire 8b 4. EQ-5D-5L 5. Insomnia Severity Index (ISI) 6. Pittsburgh Sleep Quality Index (PSQ-I) 7. St George's Respiratory Questionnaire (SGRQ) 8. COPD Assessment Test (CAT)

Chronic Obstructive Pulmonary Disease (COPD); Control; Obstructive Sleep Apnoea (OSA); Overlap Syndrome (OVS)

Pulmonary Function Test (PFT) DIAGNOSTIC_TEST

Full pulmonary function testing will be conducted in control, COPD, OSA and overlap syndrome groups. Full lung function testing will include spirometry with pre and post bronchodilator, oscillometry, lung diffusion testing (DLCO) and lung volumes.

Chronic Obstructive Pulmonary Disease (COPD); Control; Obstructive Sleep Apnoea (OSA); Overlap Syndrome (OVS)

Cognitive Assessment OTHER

The following cognitive assessments will be administered using a digital format on CANTAB: 1. Motor Screening Task (MOT) Used to assess sensorimotor function and comprehension and is applicable in the assessment of general cognitive function, Alzheimer's disease and cerebrovascular disease. This task acts as a practice trial for the subsequent tasks. 2. Reaction Time (RTI) Used to assess processing and psychomotor speed and is applicable in the assessment of general cognitive function and Alzheimer's disease. 3. Paired Associate Learning (PAL) Used to assess visual episodic memory and is applicable in the assessment of general cognitive function, Alzheimer's disease, Parkinson's disease and cerebrovascular disease. 4. Spatial Working Memory (SWM) Used to assess working memory and strategy and is applicable in the assessment of general cognitive function, Alzheimer's disease and cerebrovascular disease.

Chronic Obstructive Pulmonary Disease (COPD); Control; Obstructive Sleep Apnoea (OSA); Overlap Syndrome (OVS)

Polysomnogram (PSG) DIAGNOSTIC_TEST

During the sleep study, physiological signals are recorded to capture eye movements (electrooculogram, EOG) and chin muscle movements (electromyogram, EMG). A nasal airflow piece, two respiratory inductance plethysmography (RIP) bands and an oximeter probe on the finger will monitor breathing and oxygen levels in the blood. Electrocardiogram (ECG), leg movements, sleeping position and snoring are also recorded.

Chronic Obstructive Pulmonary Disease (COPD); Control; Obstructive Sleep Apnoea (OSA); Overlap Syndrome (OVS)

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population involves four groups: controls, OSA, COPD and overlap syndrome (OVS). All participants will meet all inclusion criteria for their group and none of the exclusion criteria.

You may qualify if:

• Control:
• Males and females;
• Aged 40-65 years;
• Able to give informed consent;
• Able to perform neuropsychological and cognitive testing;
• Fluent in English.
• OSA:
• Males and females;
• Aged 40-65 years;
• Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) ≥15/hr;
• Able to give informed consent;
• Ability to perform neuropsychological and cognitive testing;
• Fluent in English.
• COPD:
• Males and females;

You may not qualify if:

• Dementia diagnosis;
• At home or overnight oxygen therapy;
• Asthma diagnosis (identified with lung function bronchodilator);
• Current antipsychotic use;
• BMI \> 40;
• PAP use or OSA treatment in the last 2 months;
• Recent COPD exacerbation with change in symptomology (hospitalisation and/or steroids and/or antibiotics) within 6 weeks;
• Awake supine oxygen saturations of \< 93%;
• Sleep disorders including narcolepsy, idiopathic hypersomnia (IH), moderate-severe restless leg syndrome (RLS) or REM behaviour disorder (RBD);
• Other major comorbidities (other lung diseases, neurodegenerative disease, brain injury, severe mental illness, PTSD);
• Uncontrolled depression (impacting daily life, no use of medications or engagement with psychotherapy- dictated by physician);
• Malignancies (basal cell carcinoma accepted);
• Any contraindication for MRI.
• New York Heart Association (NYHA) score of IV or hospitalisation from heart failure in the last 6 months.

Sponsors & Collaborators

• Woolcock Institute of Medical Research: lead

Study Sites (1)

The Woolcock Institute of Medical Research

Sydney, New South Wales, 2113, Australia

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood collection and analyses will involve apolipoprotein 4 (APOE4) with consent

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Magnetic Resonance Imaging; Blood Specimen Collection; Surveys and Questionnaires; Respiratory Function Tests; Mental Status and Dementia Tests; Polysomnography

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Diagnostic Techniques, Respiratory System; Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities; Monitoring, Physiologic

Central Study Contacts

Angela D'Rozario

CONTACT

02 9850 3246; angela.drozario@mq.edu.au

Laura Harris

CONTACT

02 9805 3194; laura.harris@woolcock.org.au

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2023
• First Posted: April 22, 2024
• Study Start: December 1, 2023
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: April 22, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will become available upon collection. Data will be available for a minimum of 15 years.
• Access Criteria: n=26 obstructive sleep apnoea (OSA) participants will meet all of the OSA inclusion criteria and none of the exclusion criteria.

Locations

AU (1)