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

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.

Altered Microstructural Changes Detected by Diffusion Kurtosis Imaging in Patients With Cognitive Impairment After Acute Cerebral Infarction

“…Therefore, pathological changes often occur in the corpus callosum, even when ischemia or hypoxia is mild. Previous studies reported that the strongest associations between abnormal DTI parameters and cognitive decline were in the corpus callosum and corona radiata ( 14 , 37 – 41 ). In our study, we also found that abnormalities of the corpus callosum and DKI parameters were strongly represented.…”

Clinical and cognitive correlates tractography analysis in patients with white matter hyperintensity of vascular origin

“…Our study found that hypertension scores and MoCA scores show a significant correlation with decreased connectivity in corpus callosum and ILF. Previous studies have reported that disruption of the corpus callosum microstructure especially the WMHL penumbra of the corpus callosum body may contribute to cognitive deficits associated with subcortical ischemic vascular disease (Qiu et al, 2021). Microstructural disruption of the right IFOF and ILF contributes to WMHL-related cognitive impairment (Chen et al, 2020) which is basically consistent with our research results, the effect of WMHL on the microstructural integrity of WM tracts may propagate along tracts to distal regions beyond the penumbra (Liu et al, 2021), In addition, in our study, decreased connectivity in left thalamoparietal pathways and left cerebellar were negatively correlated with MoCA scores.…”

Association between white matter alterations and domain-specific cognitive impairment in cerebral small vessel disease: A meta-analysis of diffusion tensor imaging

“…Damage to the frontal–subcortical network can occur in the form of white matter lesions or microbleeds affecting pathways that connect cortical and subcortical regions, which result in cognitive impairments in executive function and attention (Ye and Bai, 2018 ). It is widely thought that white matter tracts in the CC harbor commissural fibers connecting the frontal lobe (FL) and other cortical areas, which can be damaged at the early stage of CSVD (Qiu et al, 2021 ). Overwhelming evidence indicates that brain network disorders lead to cognitive impairment of CSVD, and damaged network structure accounts for the association between CSVD neuroimaging lesions and cognitive deficits (Vasquez and Zakzanis, 2015 ).…”