Leukoaraiosis Mediates the Association of Total White Blood Cell Count With Post-Stroke Cognitive Impairment.

Wanying Shan,Yuan Xu,Jie Zhao,Zhuoyin Qiu,Jie Feng,Liang Xu,Jingwen Wang

doi:10.3389/fneur.2021.793435

Abstract

Background and PurposeThe inflammatory response could play a key role in cognitive impairment. However, there has been limited research into the association between total white blood cell (WBC) count and post-stroke cognitive impairment (PSCI), and the significance of leukoaraiosis (LA) in this relationship is unknown. We aimed to examine the total WBC count in relation to PSCI and whether this association was mediated by LA.MethodsConsecutive patients with first-ever ischemic stroke were prospectively enrolled from October 2020 to June 2021. The total WBC count was measured after admission. Cognitive function evaluations were performed at the 3-month follow-up using Mini-mental State Examination (MMSE). We defined the PSCI as an MMSE score <27.ResultsA total of 276 patients (mean age, 66.5 years; 54.7% male) were included in this analysis. Among them, 137 (49.6%) patients experienced PSCI. After adjustment for potential confounders, higher total WBC count was significantly correlated with an increased risk of LA [per 1-SD increase, odds ratio (OR), 1.39; 95% CI 1.06–1.82; p = 0.017] and PSCI (per 1-SD increase, OR, 1.51; 95% CI 1.12–2.04; p = 0.006). Furthermore, mediation analysis demonstrated that the association between total WBC count and PSCI was partly mediated by LA (the regression coefficient was changed by 9.7% for PSCI, and 12.4% for PSCI severity, respectively).ConclusionIncreased total WBC count is a risk factor for PSCI. The presence of LA was partially responsible for the PSCI in patients who had a higher total WBC count.

Highlights

In China, ischemic stroke has been ranked as the first leading cause of major disability and death [1]
Determining the exact biomarkers and potential mechanisms for Post-stroke cognitive impairment (PSCI) is of vital importance for continuously improving the prognosis of patients with ischemic stroke
The risk was slightly attenuated but persisted after adjustments for age, sex, education years, diabetes mellitus, baseline National Institutes of Health Stroke Scale (NIHSS) score, DWI-ASPECTS 0–7, uric acid, and high-sensitivity C-reactive protein (Hs-CRP) level (OR, 2.00; 95% CI 1.03–4.20; FIGURE 2 | The mediation analysis by leukoaraiosis (LA) of the association between the total white blood cell (WBC) count and cognitive impairment [(A) for PSCI; (B) for PSCI severity]. (a) Regression coefficient of the association between total WBC count and cognitive impairment; (b) the regression coefficient of the association between LA and cognitive impairment, using total WBC count and LA as independent variables; (c) regression coefficient of the association between total WBC count and cognitive impairment; (c′ ) regression coefficient of the association between total WBC count and cognitive impairment, using total WBC count and leukoaraiosis as independent variables

Summary

Introduction

In China, ischemic stroke has been ranked as the first leading cause of major disability and death [1]. Post-stroke cognitive impairment (PSCI) is the most common complication with a prevalence ranging from 20 to 80% [2]. PSCI is reported to influence the performance in daily life and at work [4] and increase the risk of long-term mortality [5]. Higher Total WBC Count in PSCI following a stroke, such as advanced age, female gender, education, and vascular comorbidities [2]. Determining the exact biomarkers and potential mechanisms for PSCI is of vital importance for continuously improving the prognosis of patients with ischemic stroke. There has been limited research into the association between total white blood cell (WBC) count and post-stroke cognitive impairment (PSCI), and the significance of leukoaraiosis (LA) in this relationship is unknown.

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