Abstract
BACKGROUND: S100A8/A9 (S100 calcium-binding protein A8/A9) was suggested to play pathophysiological roles in the amyloid-neuroinflammatory cascade, contributing to cognitive impairment. However, little is known about the impacts of S100A8/A9 on poststroke cognitive impairment. We aimed to prospectively investigate the relationships between baseline plasma S100A8/A9 levels with cognitive impairment among patients with acute ischemic stroke. METHODS: Our prospective cohort study included patients with acute ischemic stroke from an ancillary study of CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). At the 3-month follow-up, cognitive impairment was evaluated using the Montreal Cognitive Assessment and the Mini-Mental State Examination. Logistic regression analysis was conducted to estimate the association between S100A8/A9 and the risk of poststroke cognitive impairment (PSCI). RESULTS: A total of 618 participants were included, of whom 405 (65.5%) met the criteria for PSCI on the basis of the Montreal Cognitive Assessment, and 323 (52.3%) on the basis of the Mini-Mental State Examination. After adjusting for potential confounding factors, especially high-sensitivity C-reactive protein, the odds ratios of PSCI for participants in the highest tertile of plasma S100A8/A9 levels were 2.27 (95% CI, 1.37-3.75) for Montreal Cognitive Assessment-defined PSCI and 1.62 (95% CI, 1.01-2.60) for Mini-Mental State Examination-defined PSCI, compared with the lowest tertile. We observed that higher baseline levels of S100A8/A9 were associated with an increased risk of cognitive impairment in a linear dose-response manner (P for linearity=0.030 for Montreal Cognitive Assessment; P for linearity=0.018 for Mini-Mental State Examination). CONCLUSIONS: Higher baseline plasma levels of S100A8/A9 were associated with an increased risk of PSCI, suggesting the potential role of S100A8/A9 as a valuable predictive biomarker for PSCI.