Erythrocytes Are an Independent Protective Factor for Vascular Cognitive Impairment in Patients With Severe White Matter Hyperintensities.

Wenjing Tang,Zihan Chang,Chen Yang,Wenjie Zhang,Siyuan Wu,Danheng Mo,Hang Zhou,Qing Wang,Yuqi Luo,Xi Tao,Yiheng Zeng

doi:10.3389/fnagi.2022.789602

Abstract

Background and Purpose: Hemoglobin is one of the main proteins in erythrocytes. There are significant correlations between low hemoglobin and white matter hyperintensities (WMH) and cognitive impairment. This study explored whether erythrocytopenia has predictive value for vascular cognitive impairment (VCI) in patients with WMH.Method: We conducted a cross-sectional study of 302 patients, including 62 with cerebral small vessel disease and 240 with stroke. Basic demographic data and fasting blood were collected. First, all patients were divided into normal cognition (NC), mild VCI (mVCI), and severe VCI (sVCI) groups (subgroups later) based on cognitive behavior scores. Second, all patients were divided into mild WMH (mWMH) and severe WMH (sWMH) groups based on Fazekas scores. The differences in blood markers between different groups or subgroups with different cognitive levels were analyzed by univariate analysis. Then, binary logistic regression was used to analyze the diagnostic value of erythrocyte counts for VCI in the sWMH group, and ordinal logistic regression was used to analyze the predictive value of multiple variables for different cognitive levels.Results: Univariate analysis showed that erythrocytes, hemoglobin, high-sensitivity C-reactive protein, retinol binding protein and prealbumin were potential blood markers for different cognitive levels in sWMH patients. Among them, erythrocytopenia has good predictive value for the diagnosis of mVCI (AUC = 0.685, P = 0.008) or sVCI (AUC = 0.699, P = 0.003) in patients with sWMH. Multivariate joint analysis showed that erythrocytes were an independent protective factor reducing the occurrence of VCI in patients with sWMH (OR = 0.633, P = 0.045). Even after adjusting for age, there was still a significant difference (P = 0.047).Conclusion: Erythrocytes are an independent protective factor for VCI in patients with sWMH. Promoting hematopoietic function may have potential value for prevention of cognitive decline in patients with cerebrovascular disease.

Highlights

Vascular cognitive impairment (VCI) is a common concomitant symptom in stroke patients and an initial symptom in patients with cerebral small vessel disease (CSVD)
We found that there was a significant difference between CSVD and stroke groups with different cognitive impairments (P = 0.001)
The proportion of severe White matter hyperintensities (WMH) (sWMH) was higher in the stroke group (122/240) than that in the CSVD group (20/62), P = 0.009

Summary

Introduction

Vascular cognitive impairment (VCI) is a common concomitant symptom in stroke patients and an initial symptom in patients with cerebral small vessel disease (CSVD). Long-term and progressive cognitive impairment will develop into vascular dementia, which has become the type of dementia second only to Alzheimer’s disease (AD) in worldwide prevalence (Wang T. et al, 2020; Deng et al, 2021; Zhu et al, 2021a). Studies examining blood biomarkers of VCI have mainly focused on vascular endothelial dysfunction (Cao Y. et al, 2021) and have been limited to a certain type of disease, such as CSVD or stroke (Zhu et al, 2019; Wang Y. et al, 2021). There are significant correlations between low hemoglobin and white matter hyperintensities (WMH) and cognitive impairment. This study explored whether erythrocytopenia has predictive value for vascular cognitive impairment (VCI) in patients with WMH

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