Background / Purpose: Little is known about the role of receptor for advanced glycation end products (RAGE) -mediated signaling in the development of vascular cognitive impairment (VCI). The study aimed to investigate the associations of various RAGE signaling related plasma biomarkers and the development of VCI in chronic ischemic stroke (IS) patients.
Methods: This cross-sectional study recruited patients with IS at an university medical center stroke clinic. VCI was defined as the scale of Clinical Dementia Ranking (CDR) ≥1. Standard enzyme-linked immunosorbent assay was used to measure the plasma concentration of soluble form of RAGE (sRAGE), endogenous soluble form of RAGE (esRAGE), high mobility group box 1 (HMGB1) and matrix metallopeptidase 9 (MMP9) in IS patients with and without VCI.
Results: Between November 2014 to October 2015, a total of 172 IS patients (mean age 72.1±7.5 years, 64.5% male) were recruited, including 73 with CDR=0, 63 with CDR=0.5 and 36 with CDR ≥1. In univariate analysis, IS patients with VCI were older, and had more diabetes mellitus, fewer atrial fibrillation, and higher post-stroke modified Rankin Scales than those without. Plasma levels of sRAGE and esRAGE, but not HMGB1 or MMP9 were significantly higher in IS patients with VCI than those without (1.44±1.29 versus 1.03±0.48 and 0.39±0.40 versus 0.24±0.13 ng/ml, both p<0.01). Importantly, both parameters remained independent after adjustment for clinical variables (OR 2.683, p=0.013 and OR 39.192, p=0.006, respectively).
Conclusion: Among IS patients, plasma levels of both sRAGE and esRAGE were elevated in those with VCI.