Sleep dysfunction, cerebral small vessel disease burden and cognitive impairment in patients with stroke

Abstract

Stroke is the second leading cause of death and a major cause of disability worldwide. Sleep dysfunction, including obstructive sleep apnea (OSA) and poor sleep quality, are prevalent but often neglected in stroke patients. Although it is estimated that over 70% of stoke patients suffer from OSA, and up to 40% experience insomnia following stroke, only around 6% are offered an official sleep test. Cerebral small vessel disease (CSVD) and cognitive impairment are commonly encountered in stroke patients. CSVD contributes to 25% of stroke and 45% of dementia globally; while up to 50% of stroke patients experience neurocognitive disorders. To date, little is known about the determinants of high OSA prevalence in the stroke population, and the relationship of sleep dysfunction with CSVD burden or cognitive impairment following stroke.

The studies described in my PhD thesis have four key aims: 1) to systematically assess the prevalence and determinants of OSA in stroke population; 2) to explore the association of OSA status with CSVD burden in stroke patients; 3) to investigate the association of sleep quality with CSVD burden in stroke patients; and 4) to evaluate the impact of sleep disturbances on the longitudinal cognitive trajectory following stroke.

In Study 1, a meta-analysis on prevalence of sleep apnea in stroke population was performed using random-effects models. In Study 2-4, patients with newly diagnosed transient ischemic attack (TIA) or minor stroke (National Institute of Health Stroke Scale <7) were recruited from the Acute Stroke Unit and TIA/Minor Stroke Clinics of Queen Mary Hospital, Hong Kong from 2018 to 2021. The clinical, neuroimaging, sleep (sleep questionnaires and actigraphy), and cognitive data were collected at baseline; sleep questionnaires and cognitive assessments were repeated at one-year visit. An overnight home sleep apnea test (HSAT) within one year was performed for patients who were eligible and willing to join the HSAT sub-study. The associations of OSA status or subjective/objective sleep quality with CSVD burden were examined using logistic regression models, respectively. The impacts of sleep dysfunctions on longitudinal cognitive changes were assessed using linear regression models and linear mixed models, accordingly.

There are several important findings in this thesis. First, the prevalence of OSA is around 71% in stroke population, and appears to differ in patients with different subtypes, location, etiology of stroke. Second, presence of high OSA-risk estimated by STOP- BANG, and HSAT-derived oxygen desaturation indices [oxygen desaturation index (ODI) and desaturation duration] other than the conventional apnea-hypopnea index (AHI) were independently associated with global CSVD burden in stroke patients. Third, objective/subjective total time in bed, duration and frequency of awakening quantified by actigraphy were associated with global CSVD burden in stroke patients. Finally, moderate-severe OSA, greater oxygen desaturation indicated by minimum SpO2, and short sleep duration were associated with an impaired cognitive trajectory over one year after stroke. These findings highlight sleep dysfunction as a potential modifiable risk factor in the pathogenesis of CSVD and cognitive impairment following stroke. Early screening and management of sleep dysfunction in patients with stroke is recommended.