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

J Am Heart Assoc. 2018 Jan 6;7(1):e007776. doi: 10.1161/JAHA.117.007776.

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.

Keywords: Mini‐Mental State Examination; Montreal Cognitive Assessment; cognitive impairment; ischemic stroke; matrix metalloproteinase‐9.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Brain Ischemia / blood*
  • Brain Ischemia / complications
  • Brain Ischemia / diagnosis
  • Brain Ischemia / psychology
  • China
  • Cognition Disorders / diagnosis
  • Cognition Disorders / etiology*
  • Cognition Disorders / psychology
  • Cognition*
  • Disability Evaluation
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / blood*
  • Mental Status and Dementia Tests
  • Middle Aged
  • New Orleans
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Stroke / blood*
  • Stroke / complications
  • Stroke / diagnosis
  • Stroke / psychology
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers
  • MMP9 protein, human
  • Matrix Metalloproteinase 9