Investigating the Neuropathology of Obstructive Sleep Apnoea
Condition: Obstructive Sleep Apnoea; Inflammation
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Inflammation
Study type: Observational

Summary: 
      Our multi-disciplinary research group works closely with people who have obstructive sleep
      apnoea. This is a life-long illness that causes breathing to stop during sleep, which leads
      to low-oxygen in the blood. Breathing restarts when the airway at the back of the throat
      reopens, usually during arousal from sleep. In some people the repeated arousals from sleep
      cause daytime sleepiness. Our research has shown that the low blood oxygen levels affect
      thinking and feeling, and in some cases we think it damages the brain cells involved with
      memory, attention, emotions and decision-making.

      This study will investigate the relationship between the amount of oxygen in the blood and
      the loss (if any) of brain cells. Also how the ability to perform complex tasks is affected
      in patients that suffer from sleep apnoea. The results will show whether the brain damage in
      patients with sleep apnoea can be reversed with treatment. These findings will guide doctors
      in the treatment for sleep apnoea and they will cast light onto the process of memory decline
      with the aim to preserve brain function.
    

Detailed description: 
      This is a cross-sectional physiological study, which is anticipated to last for 4 years. In
      order to study the mechanism of cognitive dysfunction in Obstructive Sleep Apnoea (OSA),
      patients will start Continuous Positive Airway Pressure (CPAP) treatment following the
      confirmed diagnosis of sleep apnoea. CPAP is the treatment of choice for patients with
      moderate to severe OSA who are sleepy during the day. It is also used in patients with mild
      OSA if they are excessively sleepy or suffer from cardiovascular risk factors. It is
      recommended by the National Institute for Clinical Excellence (NICE) as a treatment for
      adults with moderate or severe OSA (Sleep apnoea - continuous positive airway pressure, NICE
      2008). In the proposed study the initiation of CPAP will be within the 18 week period set out
      in the National Health Service (NHS) Improvement Plan and Standards for Better Health
      (Standards for Better Health, Department of Health 2004). No patient with a diagnosis of OSA
      will commence treatment with CPAP later than advised by the NICE guidelines of clinical
      judgement for the best interest of the patient.

      In order to investigate the neuroinflammation process and discrete changes in the brain of
      patients with OSA, a minimum of 9 patients with mild OSA and 9 patients with severe OSA will
      be compared to 9 healthy controls following initial sleep (assessment) study. All
      participants will undergo a dynamic Positron Emission Tomography with Magnetic Resonance
      Imaging (PET-MR) scan with the Translocator protein (TSPO) tracer [Fluorine-18]
      N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide
      (DPA-714) at the time of enrolment to the study. Each participant will also have an MRI scan
      and cognitive testing.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Patient group:

          -  Untreated patients with mild Sleep Apnoea - Apnoea-Hypopnoea Index (AHI) >5
             events/hour and <10 events/hour with excessive sleepiness (Epworth sleepiness score
             >9).

          -  Untreated patients with severe Sleep Apnoea - AHI >30 events/hour with excessive
             sleepiness (Epworth sleepiness score >9).

        Healthy control group:

          -  Male participants

          -  No history of sleep disorders

          -  AHI≤5/hour

          -  No current or previous major neurological or psychiatric disease

          -  Not currently undertaking neuropharmacological treatment

          -  Non-smoker

          -  No history of alcohol or recreational drug abuse, major organ failure

          -  Not professional drivers or shift workers.
      
Biospecimen description: 
      Participants will be invited to donate samples (blood or saliva) to the Biomedical Research
      Centre (BRC) Bioresource. In order to have statistical power for genetic analysis, samples
      from INcOSA participants will need to be combined with those from the OSA BioResource
      (Research Tissue Bank) volunteers who have provided consented biological samples for future
      research.

      These samples may be used for genetic, epigenetic, metabolomic or proteomic analysis.
    
Keywords: cognitive function; microglia; neuroinflammation