An association between neuroinflammation and cognitive decline has been established. The complement system regulates neuroinflammation. Dysregulation, impairment or inadvertent activation of complement components contribute to preclinical Alzheimer's disease. The astrocyte-derived exosome (ADE) complement proteins, including C3b and C5b-9, may be predictive biomarkers of mild cognitive impairment conversion to Alzheimer's disease dementia. We hypothesized that complement proteins might be involved in cognitive impairment during obstructive sleep apnea (OSA). The aim of our study was to explore the correlation between the complement system and mild cognitive impairment (MCI) in patients with OSA.

All participants with subjective snoring complaints from the Sleep Medicine Center underwent polysomnography. OSA was defined as apnea-hypopnea index (AHI) ≥ 5 events/hour. MCI was defined as the MoCA < 26 and met the criteria: (1) a subjective cognitive impairment; (2) an objective impairment in one or more cognitive domains; (3) complex instrumental daily abilities can be slightly impaired but independent daily living abilities are maintained; and (4) no dementia. The ADEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of complement proteins, including C3b, C5b-9, and CD55. The participants who received CPAP were followed up and their complement protein levels were reassessed after 1 year of treatment.

A total of 212 participants (66.98% males; mean age of 56.71±10.10 years) were divided into the OSA+MCI group (n=90), OSA-MCI group (n=79), and controls (normal cognitive state without OSA) (n=43). The ADE levels of C3b and C5b-9 in the OSA+MCI group were higher than those in the OSA-MCI and control groups. The C3b and C5b-9 were independently associated with cognitive impairment in patients with OSA. The relationship between AHI and MoCA scores was mediated by C3b and C5b-9. We found no linear correlation between the complement proteins and the severity of OSA. The complement proteins were negatively correlated with global cognitive performance and cognitive subdomains. The complement protein levels significantly decreased after CPAP treatment.

Complement proteins were implicated in cognitive impairment in patients with OSA and may be promising biomarkers for predicting cognitive impairment in patients with OSA.

Registry: Chinese Clinical Trial Registry; URL: http://www.chictr.org.cn/; Identifier: ChiCTR1900021544; Name: Study on early diagnostic markers in patients with dementia and mild cognitive impairment.