The receptor for advanced glycation end products (RAGE) and its downstream pathways are involved in various inflammatory and immune responses. Importantly, there is soluble RAGE (sRAGE) that forms either by alternative splicing of RAGE messenger ribonucleic acid as the endogenous soluble form of RAGE (esRAGE) or by proteolytic cleavage of full-length RAGE protein. This study aimed to investigate the associations of the plasma levels of sRAGE and esRAGE in ischemic stroke (IS) patients with and without dementia. This cross-sectional study recruited patients with IS at a university medical center. Vascular dementia was defined as the scale of Clinical Dementia Ranking (CDR) ≥ 1. Standard enzyme-linked immunosorbent assay was used to measure the plasma concentration of sRAGE and esRAGE. From 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 dementia were older and had more diabetes mellitus, less atrial fibrillation, and higher post-stroke modified Rankin Scale scores than those without dementia. Plasma levels of sRAGE and esRAGE were significantly higher in IS patients with than those without dementia (1.44 ± 1.29 vs. 1.03 ± 0.48 and 0.39 ± 0.40 vs. 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). In summary, plasma sRAGE and esRAGE were elevated in those with dementia compared with those without dementia among IS patients.
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