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Serum Matrix Metalloproteinase-9 and Cognitive Impairment After Acute Ischemic Stroke.

ABSTRACT: BACKGROUND:The impact of serum matrix metalloproteinases-9 (MMP-9) on cognitive impairment after ischemic stroke is unclear. We aimed to investigate the association between serum MMP-9 in the short-term acute phase of ischemic stroke and cognitive impairment at 3 months. METHODS AND RESULTS:Our study was based on a subsample from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke); a total of 558 patients with serum MMP-9 levels from 7 of 26 participating sites of the trial were included in this analysis. Cognitive impairment severity was categorized as severe, mild, or none (Mini-Mental State Examination score, <23, 23-26, or ≥27, respectively; Montreal Cognitive Assessment score, <20, 20-24, or ≥25, respectively). Cognitive impairment was defined as a score of <27 for Mini-Mental State Examination or <25 for Montreal Cognitive Assessment. According to Mini-Mental State Examination score, 143 participants (25.6%) had mild cognitive impairment and 153 (27.4%) had severe cognitive impairment at 3 months. After adjustment for age, National Institutes of Health stroke score, education, and other covariates, the odds ratio for the highest quartile of serum MMP-9 compared with the lowest quartile was 3.20 (95% confidence interval, 1.87-5.49) for cognitive impairment. Multiple-adjusted spline regression model showed a linear association between MMP-9 levels and cognitive impairment (P<0.001 for linearity). Sensitivity and subgroup analyses further confirmed these results. Similar significant findings were observed when cognitive impairment was defined by Montreal Cognitive Assessment score. CONCLUSIONS:Increased serum MMP-9 levels in the short-term phase of ischemic stroke were associated with 3-month cognitive impairment, independently of established risk factors.

SUBMITTER: Zhong C

PROVIDER: S-EPMC5778973 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPost-stroke cognitive impairment (PSCI) is a common complication after stroke, but effective therapy is limited. Identifying potential risk factors for effective intervention is warranted. We investigated whether serum superoxide dismutase (SOD) levels were related to cognitive impairment after mild acute ischemic stroke (AIS) by using a prospective cohort design.MethodsA total of 187 patients diagnosed with mild AIS (National Institutes of Health Stroke Scale ≤ 8) were recruited. Serum SOD, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were measured, and cognitive assessments (Mini-Mental State Examination, MMSE; Montreal Cognitive Assessment, MoCA) were performed in the early phase (within 2 weeks). These indexes and assessments were repeated at 3 months after onset. MoCA < 22 was defined as early cognitive impairment (CI-E) within 2 weeks and late cognitive impairment (CI-L) at 3 months after stroke.ResultsIn a survey, 105 of 187 (56.1%) patients were identified as CI-E after mild AIS. Lower serum SOD associated with higher inflammatory biomarkers (ESR, CRP, and IL-6) and worse cognitive scores was observed in CI-E patients. In a survey, 39 of 103 (37.9%) stroke patients who completed the 3-month follow-up were identified as CI-L. Serum SOD was consistently lower in CI-L patients at baseline and 3 months and positively associated with cognitive scores. In adjusted analyses, low serum SOD at baseline was independently associated with high risks of CI-E and CI-L, with odds ratios (ORs) of 0.64 and 0.33 per standard deviation increase in serum SOD, respectively. Multiple-adjusted spline regression models showed linear associations between serum SOD and CI-E (P = 0.044 for linearity) and CI-L (P = 0.006 for linearity). Moreover, 35.2% (19/54) of CI-E patients cognitively recovered during the 3-month follow-up. In multivariable analysis, SOD was identified as a protective factor for cognitive recovery after stroke (OR 1.04, 95% CI: 1.01-1.08, P = 0.024).ConclusionWe demonstrate that low serum SOD is associated with a high risk of cognitive impairment after mild AIS, indicating SOD may be a potential modifiable factor for PSCI.

Project description:Background and Aims: Systemic inflammation is associated with an increased risk of cognitive impairment and dementia, but the associations between them in stroke patients are less clear. We examined the impact of systemic inflammation represented as the neutrophil-lymphocyte ratio (NLR) on the development of post-stroke cognitive impairment (PSCI) and domain-specific cognitive outcomes 3-month after ischemic stroke. Methods: Using prospective stroke registry data, we consecutively enrolled 345 participants with ischemic stroke whose cognitive functions were evaluated 3-month after stroke. Their cognition was assessed with the Korean version of the Vascular Cognitive Impairment Harmonization Standards and the Korean-Mini Mental Status Examination. PSCI was defined as a z-score of < -2 standard deviations for age, sex, and education adjusted means in at least one cognitive domain. The participants were categorized into five groups according to the quintiles of NLR (lowest NLR, Q1). The cross-sectional association between NLR and PSCI was assessed using multiple logistic regression, adjusting for age, sex, education, vascular risk factors, and stroke type. Results: A total of 345 patients were enrolled. The mean age was 63.0 years and the median NIHSS score and NLR were 2 [1-4] and 2.26 [1.65-2.91], respectively. PSCI was identified in 71 (20.6%) patients. NLR was a significant predictor for PSCI both as a continuous variable (adjusted OR, 1.14; 95% CI, 1.00-1.31) and as a categorical variable (Q5, adjusted OR, 3.26; 95% CI, 1.17-9.08). Patients in the Q5 group (NLR ≥ 3.80) showed significantly worse performance in global cognition and in visuospatial and memory domains. Conclusions: NLR in the acute stage of ischemic stroke was independently associated with PSCI at 3 months after stroke, and high NLR was specifically associated with cognitive dysfunction in the memory and visuospatial domains. Thus, systemic inflammation may be a modifiable risk factor that may influence cognitive outcomes after stroke.

Project description:BackgroundPoststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance.Methods and resultsThis prospective study included 566 patients with ischemic stroke. Cardiac biomarkers, including sST2 (soluble suppression of tumorigenicity-2 receptor), GDF-15 (growth differentiation factor-15), and NT-proBNP (N-terminal pro-B-type natriuretic peptide), were measured. Cognitive impairment was defined as a Mini-Mental State Examination score of <27 or a Montreal Cognitive Assessment score of <25 at 3 months after ischemic stroke. Odds of cognitive impairment 3 months after ischemic stroke increased with the number of elevated cardiac biomarkers (sST2, GDF-15, and NT-proBNP; Ptrend<0.001). The multivariable adjusted odds ratios (95% CIs) of cognitive impairment defined by the Mini-Mental State Examination and Montreal Cognitive Assessment were 2.45 (1.48-4.07) and 1.86 (1.10-3.14) for the participants with ≥2 elevated cardiac biomarkers, respectively, compared with those without any elevated cardiac biomarker. Additionally, higher cardiac biomarker scores were associated with an increased risk of cognitive impairment (Ptrend<0.05). Simultaneously adding all 3 cardiac biomarkers to the basic model with traditional risk factors significantly improved the risk prediction of Mini-Mental State Examination-defined cognitive impairment (net reclassification improvement=34.99%, P<0.001; integrated discrimination index=2.67%, P<0.001). Similar findings were observed using the Montreal Cognitive Assessment scores.ConclusionsAn increased number of elevated novel cardiac biomarkers were associated with an increased odds of poststroke cognitive impairment, suggesting that a combination of these cardiac biomarkers may improve the risk prediction of cognitive impairment.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

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Serum Matrix Metalloproteinase-9 and Cognitive Impairment After Acute Ischemic Stroke.

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