Associação entre os níveis de quimiocinas periféricas e déficits cognitivos no acidente vascular cerebral isquêmico agudo leve a moderado: um estudo transversal

Abstract

Ischemic stroke (IS) is a frequent cause of cognitive impairment, even in clinically mild to moderate cases. Neuroinflammation, mediated by circulating chemokines and inflammatory proteins, has been proposed as a link between acute ischemic injury and persistent cognitive deficits. In this context, serum biomarkers are particularly attractive as they avoid invasive sampling, allow serial assessment and fall within the therapeutic window of IS, providing a real opportunity for risk stratification and early cognitive prognosis. Despite this, the relationship between the serum profile of these mediators in the acute phase and cognitive performance remains poorly characterized in patients with mild to moderate IS. This study aimed to investigate the association between serum levels of chemokines and inflammatory proteins and cognitive performance in patients in the acute phase of mild to moderate IS. This was a cross-sectional study with a quantitative approach, based on data collected between 2019 and 2021 at the Hospital Metropolitano Odilon Behrens (HOB), a public regional referral center for neurological urgencies and the main entry point for stroke cases in Belo Horizonte (MG, Brazil) and its metropolitan area. A total of 42 participants were included: 21 patients with IS (NIHSS score 0 to 10) and 21 healthy controls matched by sex, age and education. Participants were assessed using the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB) and the Visual Memory Test (VMT). Peripheral blood samples were collected concurrently with cognitive testing for serum quantification of CCL2, CCL3, CCL4, CCL5, CCL7, CCL11, CCL22, CXCL8, MIF, MPO and Lipocalin-2 (LCN2) by a beadbased multiplex immunoassay. Statistical analyses included the Mann-Whitney and chi-square tests, simple linear regression, Spearman correlation and Receiver Operating Characteristic (ROC) curve analysis. The post-IS group showed reduced serum levels of CCL3, CCL4, CCL5 and CXCL8 and elevated levels of LCN2 compared with the control group. LCN2 was positively associated with neurological severity (NIHSS) and negatively associated with FAB performance and with immediate memory in the VMT, whereas CCL3, CCL5 and CXCL8 showed an inverse association with NIHSS. In the ROC analyses, LCN2 (area under the curve, AUC = 1.00) and CXCL8 (AUC = 0.94) stood out in discriminating between groups. Within the post-IS group, MIF discriminated patients with worse FAB performance (AUC = 0.82) and MPO discriminated patients with worse immediate memory in the 10 VMT (AUC = 0.83). The findings support the hypothesis that the serum profile of chemokines and inflammatory proteins in the acute phase of mild to moderate IS are related to neurological severity and to specific cognitive domains, highlighting LCN2 as a marker of severity and MIF and MPO as potential markers of executive and memory impairment, respectively.