Biomarkers of Dementia in Chronic Sleep and Breathing Disorders
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Blood levels of amyloid beta (Aβ40/Aβ42 ratio).
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and females;
- •Aged 40-65 years;
- •Able to give informed consent;
- •Able to perform neuropsychological and cognitive testing;
- •Fluent in English.
- •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.
- •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:
- •Males and females;
- •Aged 40-65 years;
- •Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) ≥15/hr;
- •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.
排除标准
- •Dementia diagnosis;
- •At home or overnight oxygen therapy;
- •Asthma diagnosis (identified with lung function bronchodilator);
- •Current antipsychotic use;
- •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.
结局指标
主要结局
Blood levels of amyloid beta (Aβ40/Aβ42 ratio).
时间窗: 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.
时间窗: 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.
次要结局
- 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)
- Blood levels of interleukin-8 (IL-8).(Cross-sectional/baseline only)
- Blood levels of C-reactive protein (CRP)(Cross-sectional/baseline only)
- Blood levels of neurofilament light chain (NFL).(Cross-sectional/baseline only)
- Blood levels of interleukin-6 (IL-6).(Cross-sectional/baseline only)
- Scores on the Montreal Cognitive Assessment (MoCA) neuropsychological assessment for dementia risk.(Cross-sectional/baseline only)
- Assessment of verbal learning and memory through the Rey Auditory Verbal Learning Test (RAVLT).(Cross-sectional/baseline only)
- Assessment of mild forms of cognitive dysfunction through Delis Kaplan Executive Functioning System (D-CEFS) neuropsychological assessment.(Cross-sectional/baseline only)
- Blood levels of fibrinogen.(Cross-sectional/baseline only)
- Blood levels of clusterin.(Cross-sectional/baseline only)
- Blood levels of Glial fibrillary acidic protein (GFAP).(Cross-sectional/baseline only)
- Blood levels of tumor necrosis factor alpha (TNFα).(Cross-sectional/baseline only)
- Hypoxemia as measured by pulse oximetry.(Cross-sectional/baseline only)
- Sleep Fragmentation(Cross-sectional/baseline only)
- Assessment of speed of processing and executive functioning through the Trail Making Test (TMT).(Cross-sectional/baseline only)
- Assessment of attention, perceptual speed, motor speed and visual scanning through the Symbol Digits Modalities Test (SDMT).(Cross-sectional/baseline only)
- Blood levels of 8-isoprostane(Cross-sectional/baseline only)
- Blood levels of erythrocyte sedimentation rate (ESR).(Cross-sectional/baseline only)
- Assessment of premorbid functioning and preinjury through the Test of Premorbid Functioning (TOPF).(Cross-sectional/baseline only)
- Assessment of verbal fluency through the Controlled Oral Word Association Test (COWAT).(Cross-sectional/baseline only)
- Blood levels of plasma tau.(Cross-sectional/baseline only)
- Blood levels of Apolipoprotein E gene (APOE-4).(Cross-sectional/baseline only)
- Blood levels of amyloid beta (Aβ40/Aβ42 ratio).(Cross-sectional/baseline only)