Sleep Apnea, Neurocognitive Decline and Brain Imaging in Patients With Subjective or Mild Cognitive Impairment

Exploring the Association Between Cognitive Function, Obstructive Sleep Apnea and Brain Imaging, and the Determinants of Neurocognitive Decline in Subjects With Subjective or Mild Cognitive Impairment

Obstructive sleep apnea (OSA) is recurrent episodes of partial or complete obstruction of the upper airway during sleep that causes intermittent hypoxia and sleep fragmentation and potentially lead to cardiometabolic and neurocognitive sequelae. Chronic intermittent hypoxia, sleep fragmentation of OSA, and insufficient sleep have been significantly associated with higher risks of neurocognitive impairment, including mild cognitive impairment (MCI) and Alzheimer's disease. Thus, sleep and sleep apnea might be modifiable factors to neurocognitive impairment.

Positive airway pressure (PAP) is the first line of treatment to maintain open airways for patients with OSA. Improving sleep, sleep apnea and circadian function could be a high-value intervention target to alleviate cognitive impairment and decline in subjects with mild neurocognitive impairment.

Amyloid accumulation in brain tissue is a distinct feature of Alzheimers' disease, which is associated with potential impairment of neurocognition clinically. It predicts memory decline in initially cognitively unimpaired individuals.

The study explores the associations between sleep apnea, cognitive function and cerebral imaging and the role of PAP therapy on neurocognitive trajectory in these patients with subjective cognitive impairment /mild cognitive impairment (SCI/MCI).

Obstructive sleep apnea (OSA) is recurrent episodes of partial or complete obstruction of the upper airway during sleep . Chronic intermittent hypoxia, sleep fragmentation of OSA, and insufficient sleep have been significantly associated with higher risks of neurocognitive impairment, including mild MCI and Alzheimer's disease. Thus, sleep and sleep apnea might be modifiable factors contributing towards neurocognitive impairment . Improving sleep and sleep apnea could be a high-value intervention to alleviate cognitive impairment and decline in subjects with mild neurocognitive impairment.

Amyloid accumulation in brain tissue is a distinct feature of Alzheimer's disease, which is associated with potential impairment of neurocognition clinically. It predicts memory decline in initially cognitively unimpaired individuals. Research suggested that cerebrospinal fluid amyloid-β42 levels showed significant differences in subjects with moderate/severe OSA compared with healthy control.

Investigators hypothesize that (i) OSA is a determinant of neurocognitive decline, and regular PAP therapy for OSA could reduce this decline in subjects presenting with subjective cognitive impairment (SCI) or MCI; (ii) OSA may contribute to cerebral amyloid burden in these subjects with clinical diagnosis of SCI/MCI.

This study (i) assesses the role of obstructive sleep apnea as a potential determinant of neurocognitive status and the impact of OSA therapy (CPAP or other interventions) on neurocognitive decline (ii) evaluates if OSA increases cerebral amyloid deposition using PET imaging.

Subjects are recruited from Memory clinic and who have undergone a study with sleep questionnaires, neurocognitive tests and home sleep apnea test (HSAT). Subjects with OSA (identified on HSAT) will be referred for management of OSA per usual clinical criteria. Sleep questionnaires and cognitive assessment tests will be reassessed at six months, one year, two year and 3 year, and determinants to neurocognitive changes will be analyzed.

Amyloid PET-MRI brain will also be done at baseline. Owing to resource constraints, investigators can only provide PET-MRI investigation for 90 subjects ( 60 subjects with moderate/severe OSA to be compared with 30 subjects with no/mild OSA) .

Inclusion Criteria:

• Aged 50 - 80 years
• Diagnosis of mild cognitive impairment based on Peterson's criteria.
• Diagnosis of subjective cognitive impairment, based on the subjective complaint of cognitive impairment, but with an unremarkable assessment of the Hong Kong version of Montreal cognitive Assessment scores
• Able to speak and read Chinese
• Adequate visual and auditory to perform a cognitive test
• Subjects with moderate-severe OSA or No OSA (diagnosis based on sleep study) would be invited for baseline PET-MRI brain scan

Exclusion Criteria:

• Diagnosed psychiatric illness with or without medication, e.g. major depressive disorder.
• Other clear organic causes of cognitive impairment, e.g. vascular cognitive impairment, brain tumour, dementia with Lewy body, mild cognitive impairment with Lewy body, Parkinson's disease, normal pressure hydrocephalus, neurosyphilis, autoimmune encephalitis, substance abuse, history of alcohol abuse.
• Diagnosis of cancer on active treatment
• Contraindications to PET-CT or MRI brain scan (excluded for neuroimaging studies)