Biomarkers of Dementia in Chronic Sleep and Breathing Disorders

Last updated: April 16, 2024
Sponsor: Woolcock Institute of Medical Research
Overall Status: Active - Recruiting

Phase

N/A

Condition

Dermatomyositis (Connective Tissue Disease)

Dementia

Treatment

Blood collection

Magnetic resonance imaging (MRI)

Neuropsychological battery

Clinical Study ID

NCT06377332
X23-0330
  • Ages 40-65
  • All Genders
  • Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

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:
  6. Males and females;
  7. Aged 40-65 years;
  8. Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) ≥15/hr;
  9. Able to give informed consent;
  10. Ability to perform neuropsychological and cognitive testing;
  11. Fluent in English. COPD:
  12. Males and females;
  13. Aged 40-65 years;
  14. COPD confirmed by diagnosis or a positive lung function test (GOLD 2 minimum, FEV1 ≥50%, < 80% predicted; FEV1/FVC < 0.7);
  15. 10-pack year smoking history;
  16. Able to perform neuropsychological and cognitive testing;
  17. Fluent in English. Overlap Syndrome:
  18. Males and females;
  19. Aged 40-65 years;
  20. Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) ≥15/hr;
  21. COPD confirmed by diagnosis or a positive lung function test (GOLD 2 minimum, FEV1 ≥50%, < 80% predicted; FEV1/FVC < 0.7);
  22. 10-pack year smoking history;
  23. Able to perform neuropsychological and cognitive testing;
  24. Fluent in English.

Exclusion

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 steroidsand/or antibiotics) within 6 weeks;
  8. Awake supine oxygen saturations of < 93%;
  9. Sleep disorders including narcolepsy, idiopathic hypersomnia (IH), moderate-severerestless leg syndrome (RLS) or REM behaviour disorder (RBD);
  10. Other major comorbidities (other lung diseases, neurodegenerative disease, braininjury, severe mental illness, PTSD);
  11. Uncontrolled depression (impacting daily life, no use of medications or engagementwith 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 inthe last 6 months.

Study Design

Total Participants: 104
Treatment Group(s): 9
Primary Treatment: Blood collection
Phase:
Study Start date:
December 01, 2023
Estimated Completion Date:
July 01, 2025

Study 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.

Connect with a study center

  • The Woolcock Institute of Medical Research

    Sydney, New South Wales 2113
    Australia

    Active - Recruiting

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