Loss of Integrity of Corpus Callosum White Matter Hyperintensity Penumbra Predicts Cognitive Decline in Patients With Subcortical Vascular Mild Cognitive Impairment.

Yage Qiu,Ling Yu,Jianrong Xu,Yawen Sun,Xin Ge,Xiaowei Wu,Qun Xu,Yao Wang,Yan Zhou

doi:10.3389/fnagi.2021.605900

Abstract

Loss of white matter (WM) integrity contributes to subcortical vascular mild cognitive impairment (svMCI). Diffusion tensor imaging (DTI) has revealed damage beyond the area of WM hyperintensity (WMH) including in normal-appearing WM (NAWM); however, the functional significance of this observation is unclear. To answer this question, in this study we investigated the relationship between microstructural changes in the WMH penumbra (WMH-P) and cognitive function in patients with svMCI by regional tract-based analysis. A total of 111 patients with svMCI and 72 patients with subcortical ischemic vascular disease (SIVD) without cognitive impairment (controls) underwent DTI and neuropsychological assessment. WMH burden was determined before computing mean values of fractional anisotropy (FA) and mean diffusivity (MD) within WMHs and WMH-Ps. Pearson’s partial correlations were used to assess the relationship between measurements showing significant intergroup differences and composite Z-scores representing global cognitive function. Multiple linear regression analysis was carried out to determine the best model for predicting composite Z-scores. We found that WMH burden in the genu, body, and splenium of the corpus callosum (GCC, BCC, and SCC respectively); bilateral anterior, superior, and posterior corona radiata; left sagittal stratum was significantly higher in the svMCI group than in the control group (p < 0.05). The WMH burden of the GCC, BCC, SCC, and bilateral anterior corona radiata was negatively correlated with composite Z-scores. Among diffusion parameters showing significant differences across the 10 WM regions, mean FA values of WMH and WMH-P of the BCC were correlated with composite Z-scores in svMCI patients. The results of the multiple linear regression analysis showed that the FA of WMH-P of the BCC and WMH burden of the SCC and GCC were independent predictors of composite Z-score, with the FA of WMH-P of the BCC making the largest contribution. These findings indicate that disruption of the CC microstructure—especially the WMH-P of the BCC—may contribute to the cognitive deficits associated with SIVD.

Highlights

Age-related cognitive impairment (CI) is a significant public health concern that will become increasingly prevalent with the aging of the global population (Iadecola et al, 2019; Kaneshwaran et al, 2019)
WM hyperintensity (WMH), white matter hyperintensity; WMH penumbra (WMH-P), white matter hyperintensity penumbra; FA, fractional anisotropy; MD, mean diffusivity (MD values are not marked in unit since being post-processed); svMCI, subcortical vascular mild cognitive impairment; GCC, genu of corpus callosum; BCC, body of corpus callosum; SCC, splenium of corpus callosum; ACR.R, right anterior corona radiata; ACR.L, left anterior corona radiata; SCR.R, right superior corona radiata; SCR.L, left superior corona radiata; PCR.R, right posterior corona radiata; PCR.L, left posterior corona radiata; SS.L, left sagittal stratum. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001
We found that the WMH burden in some parts of the CC and corona radiata was significantly higher in patients with svMCI than in control subjects

Summary

Introduction

Age-related cognitive impairment (CI) is a significant public health concern that will become increasingly prevalent with the aging of the global population (Iadecola et al, 2019; Kaneshwaran et al, 2019). CI of vascular etiology is the second leading cause of cognitive deficits after Alzheimer’s disease (AD) worldwide, and may be the predominant cause in East Asia (Iadecola et al, 2019; Lam and Mok, 2019). Subcortical VCI (SVCI), which is attributable to cerebral small vessel disease, accounts for approximately 50%–70% of VCI cases and ranges from subcortical vascular mild cognitive impairment (svMCI) to subcortical vascular dementia (SVaD; O’Brien et al, 2003; Lee et al, 2014; Shi and Wardlaw, 2016). The mechanisms of brain injury in SVCI include vessel occlusion, leakage of toxins, impaired vascular reactivity, decreased clearance of waste products, oligodendrocyte dysfunction, increased oxidation, and inflammation (Wardlaw et al, 2013). A prodromal stage of SVaD has been recognized based on the observation that the progression from svMCI to SVaD can be prevented by managing risk factors and through drug treatments (Seo et al, 2010; Lee et al, 2014; Jung et al, 2018)

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