Plasma S100 Calcium-Binding Protein A8/A9 and Cognitive Impairment After Acute Ischemic Stroke

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.

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).

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).

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.