Biomarkers of Dementia in Chronic Sleep and Breathing Disorders

Recruiting

• Conditions: COPD; Overlap Syndrome; OSA
• Interventions: 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)

• Registration Number: NCT06377332
• Lead Sponsor: Woolcock Institute of Medical Research

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.

Detailed Description

Neurodegeneration that is present in dementia is caused, in part, by neuroinflammation, cerebral vascular damage and oxidative stress. Intermittent hypoxia and hypercapnia, as seen in patients with chronic obstructive pulmonary disease (COPD), obstructive sleep apnoea (OSA) and overlap syndrome, cause neuroinflammation and sleep fragmentation. As a result, key biomarkers of cytokine tumour necrosis factor-alpha (TNF-a), C-reactive protein (CRP), eosinophils, CD8+ and CD4+ T cells, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL-1B), nuclear factor kappa beta (NF-kB) and hypoxia-inducible factor (HIF) infiltrate the central nervous system (CNS), perpetuating neuroinflammation through the presence of microglia which cause oxidative and nitrosative stress.

Key inflammatory and dementia-based biomarkers will be collected in the investigation of this association including but not limited to Aβ40/42 ratio and ptau217.

This study consists of an observational cross-sectional design with the utilisation of blood collection, lung function testing, MRI, HdEEG, fNIRS and neurocognitive assessment. Participants will be selected into the study differentially based on the target group, with OSA criteria requiring an ODI \> 15, COPD criteria requiring a GOLD 2 minimum, FEV1 ≥50%, \< 80% predicted; FEV1/FVC \< 0.7 with a 10- pack year smoking history and overlap syndrome criteria requiring a combination of ODI \> 15 and GOLD 2 minimum, FEV1 ≥50%, \< 80% predicted; FEV1/FVC \< 0.7, with a 10-pack year smoking history. Participants will be 40 to 65 years old. Controls will have no diagnosis of OSA, COPD or overlap syndrome and have an English fluency. In order to test the hypotheses, the design of a cross-sectional study will allow us to a) examine the relationships between sleep and breathing metrics and cognition and blood-based markers of dementia pathology b) examine the relationships between potential intermediates of compromised sleep and breathing with the primary cognitive and dementia risk outcomes c) compare sleep, lung function, brain health, cognition and inflammatory markers between OSA, COPD, overlap syndrome and control groups.

Study Timeline

• Status Verified: 2023-11
• Study First Submitted: 2023-11-06
• Study Start: 2023-12-01
• Study First Submitted QC: 2024-04-16
• Last Update Submitted: 2024-04-16
• Study First Posted: 2024-04-22
• Last Update Posted: 2024-04-22
• Primary Completion: 2025-07-01
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

Control:

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

OSA:

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

COPD:

1. Males and females;

2. Aged 40-65 years;

3. COPD confirmed by diagnosis or a positive lung function test (GOLD 2 minimum, FEV1

   ≥50%, < 80% predicted; FEV1/FVC < 0.7);

4. 10-pack year smoking history;

5. Able to perform neuropsychological and cognitive testing;

6. Fluent in English.

Overlap Syndrome:

1. Males and females;

2. Aged 40-65 years;

3. Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) ≥15/hr;

4. COPD confirmed by diagnosis or a positive lung function test (GOLD 2 minimum, FEV1

   ≥50%, < 80% predicted; FEV1/FVC < 0.7);

5. 10-pack year smoking history;

6. Able to perform neuropsychological and cognitive testing;

7. Fluent in English.

Exclusion Criteria

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Chronic Obstructive Pulmonary Disease (COPD)	Blood collection	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.
Overlap Syndrome (OVS)	Blood collection	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.
Overlap Syndrome (OVS)	Cognitive Assessment	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.
Overlap Syndrome (OVS)	Polysomnogram (PSG)	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.
Chronic Obstructive Pulmonary Disease (COPD)	High density electroencephalogram (HdEEG)	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.
Chronic Obstructive Pulmonary Disease (COPD)	Neuropsychological battery	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.
Chronic Obstructive Pulmonary Disease (COPD)	Pulmonary Function Test (PFT)	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.
Overlap Syndrome (OVS)	Neuropsychological battery	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.
Obstructive Sleep Apnoea (OSA)	High density electroencephalogram (HdEEG)	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.
Obstructive Sleep Apnoea (OSA)	Pulmonary Function Test (PFT)	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.
Chronic Obstructive Pulmonary Disease (COPD)	Functional near infrared spectroscopy (fNIRS)	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.
Chronic Obstructive Pulmonary Disease (COPD)	Magnetic resonance imaging (MRI)	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.
Chronic Obstructive Pulmonary Disease (COPD)	Cognitive Assessment	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.
Overlap Syndrome (OVS)	Pulmonary Function Test (PFT)	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.
Chronic Obstructive Pulmonary Disease (COPD)	Questionnaires	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.
Overlap Syndrome (OVS)	Questionnaires	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.
Obstructive Sleep Apnoea (OSA)	Magnetic resonance imaging (MRI)	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.
Obstructive Sleep Apnoea (OSA)	Blood collection	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.
Chronic Obstructive Pulmonary Disease (COPD)	Polysomnogram (PSG)	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.
Overlap Syndrome (OVS)	High density electroencephalogram (HdEEG)	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.
Overlap Syndrome (OVS)	Functional near infrared spectroscopy (fNIRS)	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.
Overlap Syndrome (OVS)	Magnetic resonance imaging (MRI)	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.
Obstructive Sleep Apnoea (OSA)	Functional near infrared spectroscopy (fNIRS)	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.
Obstructive Sleep Apnoea (OSA)	Questionnaires	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.
Control	High density electroencephalogram (HdEEG)	Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English.
Control	Pulmonary Function Test (PFT)	Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English.
Obstructive Sleep Apnoea (OSA)	Neuropsychological battery	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.
Control	Functional near infrared spectroscopy (fNIRS)	Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English.
Control	Neuropsychological battery	Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English.
Control	Polysomnogram (PSG)	Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English.
Obstructive Sleep Apnoea (OSA)	Cognitive Assessment	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.
Obstructive Sleep Apnoea (OSA)	Polysomnogram (PSG)	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.
Control	Blood collection	Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English.
Control	Cognitive Assessment	Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English.
Control	Magnetic resonance imaging (MRI)	Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English.
Control	Questionnaires	Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English.

Primary Outcome Measures

Name	Time	Method
Blood levels of amyloid beta (Aβ40/Aβ42 ratio).	Cross-sectional/baseline only	Associations between blood levels of Aβ (Aβ40/Aβ42 ratio) and night-time hypoxemia / sleep fragmentation in the entire sample.
Scores on the Montreal Cognitive Assessment (MoCA) neuropsychological assessment for dementia risk.	Cross-sectional/baseline only	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.

Secondary Outcome Measures

Name	Time	Method
Assessment of premorbid functioning and preinjury through the Test of Premorbid Functioning (TOPF).	Cross-sectional/baseline only	Neuropsychological Test: A z-score of -0.75 indicates low-average premorbid functioning, z= -1.40 indicates borderline poor premorbid functioning and inferior premorbid functioning spans from z=-2.05 to -3.65. Associations between TOPF scores and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Assessment of verbal fluency through the Controlled Oral Word Association Test (COWAT).	Cross-sectional/baseline only	Neuropsychological Test: Differences in the COWAT scores between groups. The more acceptable words stated across all four trials, the better the performance in the test. Associations between COWAT scores and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of plasma tau.	Cross-sectional/baseline only	Differences in the blood levels of plasma tau between groups. Associations between plasma-tau and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of Apolipoprotein E gene (APOE-4).	Cross-sectional/baseline only	Differences in the blood levels of APOE-4 between groups. Associations between APOE-4 and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep.	Cross-sectional/baseline only	Spectral power of delta (1-4.5 Hz), theta (4.5-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40 Hz) frequency ranges. Associations between absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Brain tissue oxygenation during cognitive tasks and sleep.	Cross-sectional/baseline only	Brain tissue oxygenation during sleep as measured by oxygenated and deoxygenated hemoglobin using functional Near Infrared Spectroscopy (fNIRS). Associations between brain tissue oxygenation and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of interleukin-8 (IL-8).	Cross-sectional/baseline only	Differences in the blood levels of IL-8 between groups. Associations between IL-8 and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of C-reactive protein (CRP)	Cross-sectional/baseline only	Differences in the blood levels of CRP between groups. Associations between CRP and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of neurofilament light chain (NFL).	Cross-sectional/baseline only	Differences in the blood levels of NFL between groups. Associations between NFL and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of interleukin-6 (IL-6).	Cross-sectional/baseline only	Differences in the blood levels of IL-6 between groups. Associations between IL-6 and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Scores on the Montreal Cognitive Assessment (MoCA) neuropsychological assessment for dementia risk.	Cross-sectional/baseline only	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 between groups.
Assessment of verbal learning and memory through the Rey Auditory Verbal Learning Test (RAVLT).	Cross-sectional/baseline only	Neuropsychological Test: RAVLT scores between groups. Scores ≤ z= -1.0 across two domains indicate poor performance. Immediate verbal learning is assessed by summing trials 1 to 5, Learning is assessed from trial 5 minus trial 1, and Forgetting is assessed through trial five minus the delayed recall trial. Associations between RAVLT scores and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Assessment of mild forms of cognitive dysfunction through Delis Kaplan Executive Functioning System (D-CEFS) neuropsychological assessment.	Cross-sectional/baseline only	Neuropsychological Test: Differences in scores between groups across the four trials. Greater time taken to complete the trials results in higher scores which indicate worse performance. Associations between D-CEFS scores night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of fibrinogen.	Cross-sectional/baseline only	Differences in the blood levels of fibrinogen between groups. Associations between fibrinogen and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of clusterin.	Cross-sectional/baseline only	Differences in the blood levels of clusterin between groups. Associations between clusterin and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of Glial fibrillary acidic protein (GFAP).	Cross-sectional/baseline only	Differences in the blood levels of GFAP between groups. Associations between GFAP and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of tumor necrosis factor alpha (TNFα).	Cross-sectional/baseline only	Differences in the blood levels of TNFα between groups. Associations between TNFα and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Hypoxemia as measured by pulse oximetry.	Cross-sectional/baseline only	Overnight hypoxemia measured by pulse oximetry through nocturnal readings of blood oxygen saturation (SpO2). Associations between night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Sleep Fragmentation	Cross-sectional/baseline only	EEG arousal index (events per minute of total sleep time) measured during polysomnography. Associations between night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Assessment of speed of processing and executive functioning through the Trail Making Test (TMT).	Cross-sectional/baseline only	Neuropsychological Test: Differences in TMT scores between groups. Greater time taken to complete the tests results in higher scores which indicate worse performance. A TMT trial A score of ≥78 seconds and a TMT trial B score of ≥273 seconds indicates deficiency. Associations between TMT scores night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Assessment of attention, perceptual speed, motor speed and visual scanning through the Symbol Digits Modalities Test (SDMT).	Cross-sectional/baseline only	Neuropsychological Test: Differences in the scores on the SDMT between groups. Scores on the SDMT range from 1 to 110, with higher scores indicating better performance over the 90-second trial. Associations between SDMT scores and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of 8-isoprostane	Cross-sectional/baseline only	Differences in the blood levels of 8-isoprostane between groups. Associations between 8-isoprostane and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of erythrocyte sedimentation rate (ESR).	Cross-sectional/baseline only	Differences in the blood levels of ESR between groups. Associations between ESR and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Blood levels of amyloid beta (Aβ40/Aβ42 ratio).	Cross-sectional/baseline only	Associations between blood levels of Aβ (Aβ40/Aβ42 ratio) and night-time hypoxemia / sleep fragmentation between groups.

Trial Locations

Locations (1)

The Woolcock Institute of Medical Research; 🇦🇺 Sydney, New South Wales, Australia