Biomarkers of Dementia in Chronic Sleep and Breathing Disorders

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

Interventions

DIAGNOSTIC_TEST

High density electroencephalogram (HdEEG)

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.

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Functional near infrared spectroscopy (fNIRS)

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.

DIAGNOSTIC_TEST

Magnetic resonance imaging (MRI)

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.

BIOLOGICAL

Blood collection

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.

DIAGNOSTIC_TEST

Neuropsychological battery

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):

OTHER

Questionnaires

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)

DIAGNOSTIC_TEST

Pulmonary Function Test (PFT)

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.

OTHER

Cognitive Assessment

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.

DIAGNOSTIC_TEST

Polysomnogram (PSG)

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.

Sponsors & Collaborators

• Woolcock Institute of Medical Research

  lead OTHER

Eligibility

Min Age

40 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-12-01

Primary Completion

2025-07-01

Completion

2025-07-01

Countries

• Australia

Study Locations