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

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.

Keywords: cerebrovascular disease; erythrocyte; high-sensitivity C-reactive protein; prealbumin; retinol binding protein; vascular cognitive impairment; white matter hyperintensities.

Figure 1

Study flow chart. Four-hundred and fourteen patients with CVD were enrolled, seven patients with suspected AD and 105 patients without MRI data were excluded, and 302 patients were included. Baseline demographic data, blood biomarkers, MRI images, and behavioral scores were collected. The patients were divided into mWMH and sWMH groups based on Fazekas scoring. A model was constructed to predict the diagnostic value of erythrocytes for VCI. AD, Alzheimer’s disease; CVD, cerebrovascular disease; mVCI, mild vascular cognitive impairment; mWMH, mild white matter hyperintensities; NC, normal cognition; sWMH, severe white matter hyperintensities; sVCI, severe vascular cognitive impairment; VCI, vascular cognitive impairment.

Figure 2

Typical WMH images in patients with CSVD and stroke. T2WI-FLAIR MRI sequences were analyzed in the patients with CSVD and/or stroke. The total Fazekas scores of typical patients with CSVD were 1 (A) and 4 (B), and those of typical stroke patients with infarction of the right basal ganglia and left occipital lobe were 1 (C) and 4 (D), respectively. Panels (A,C) were identified as mWMH, and (B,D) as sWMH. CSVD, cerebral small vessel disease; mWMH, mild white matter hyperintensities; NC, normal cognition; sWMH, severe white matter hyperintensities.

Figure 3

Box diagram of erythrocytes in the mWMH and sWMH groups and ROC curves to predict the diagnostic value of erythrocytes for mVCI and sVCI in the sWMH group. Comparison of erythrocyte counts among patients with three cognitive levels in the mWMH (A) (H = 2.993, P = 0.224) and sWMH (B) (F = 6.094, P = 0.003) groups. (C) Diagnostic value of erythrocytes to sVCI in the sWMH group [AUC = 0.699, P = 0.003, 95% CI (0.586, 0.812)]. (D) Diagnostic value of erythrocytes to mVCI in the sWMH group [AUC = 0.685, P = 0.008, 95% CI (0.561, 0.810)]. AUC, area under the ROC curve; mVCI, mild vascular cognitive impairment; mWMH, mild white matter hyperintensities; ROC, receiver operating characteristic; sWMH, severe white matter hyperintensities; sVCI, severe vascular cognitive impairment.