Abnormal static and dynamic functional connectivity of networks related to cognition in patients with subcortical ischemic vascular disease.

PURPOSE: To investigate the specific features of static functional connectivity (SFC) and dynamic functional connectivity (DFC) of networks related to cognition in patients with subcortical ischemic vascular disease (SIVD). METHODS: In this retrospective study, resting-state functional MRI data and a series of cognitive scores were obtained from 38 patients with SIVD and 23 normal controls. Independent component analysis, sliding window method, k-means clustering analysis and graph theory method were used to examine FC between the default mode network (DMN), dorsal attention network (DAN), frontoparietal network (FPN), salience network (SN) and executive control network (ECN) in patients with SIVD. Then, correlations between abnormal FC features and cognition were assessed. RESULTS: Compared with normal controls, SFC within the DMN significantly increased and SFC between the DMN and DAN significantly decreased in patients with SIVD. The decreased DFC mainly occurred in weakly connected states, especially the DFC of the SN; but the increased DFC, global network efficiency and local network efficiency and the decreased mean dwell time (MDT) and frequency mainly occurred in strongly connected states in SIVD patients. Moreover, aberrant SFC, DFC and MDT were significantly correlated with patients' cognitive scores. CONCLUSION: The overall results are suggestive of abnormal functional segregation and integration of SFC and DFC among networks related to cognition, especially in the SN. This may advance our comprehensive understanding of the abnormal changes in brain network connectivity in patients with SIVD. Our findings also highlight DFC may be an effective neuroimaging marker for the clinical diagnosis of SIVD.

Unraveling the link: white matter damage, gray matter atrophy and memory impairment in patients with subcortical ischemic vascular disease.

Introduction: Prior MRI studies have shown that patients with subcortical ischemic vascular disease (SIVD) exhibited white matter damage, gray matter atrophy and memory impairment, but the specific characteristics and interrelationships of these abnormal changes have not been fully elucidated. Materials and methods: We collected the MRI data and memory scores from 29 SIVD patients with cognitive impairment (SIVD-CI), 29 SIVD patients with cognitive unimpaired (SIVD-CU) and 32 normal controls (NC). Subsequently, the thicknesses and volumes of the gray matter regions that are closely related to memory function were automatically assessed using FreeSurfer software. Then, the volume, fractional anisotropy (FA), mean diffusivity (MD), amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values of white matter hyperintensity (WMH) region and normal-appearing white matter (NAWM) were obtained using SPM, DPARSF, and FSL software. Finally, the analysis of covariance, spearman correlation and mediation analysis were used to analyze data. Results: Compared with NC group, patients in SIVD-CI and SIVD-CU groups showed significantly abnormal volume, FA, MD, ALFF, and ReHo values of WMH region and NAWM, as well as significantly decreased volume and thickness values of gray matter regions, mainly including thalamus, middle temporal gyrus and hippocampal subfields such as cornu ammonis (CA) 1. These abnormal changes were significantly correlated with decreased visual, auditory and working memory scores. Compared with the SIVD-CU group, the significant reductions of the left CA2/3, right amygdala, right parasubiculum and NAWM volumes and the significant increases of the MD values in the WMH region and NAWM were found in the SIVD-CI group. And the increased MD values were significantly related to working memory scores. Moreover, the decreased CA1 and thalamus volumes mediated the correlations between the abnormal microstructure indicators in WMH region and the decreased memory scores in the SIVD-CI group. Conclusion: Patients with SIVD had structural and functional damages in both WMH and NAWM, along with specific gray matter atrophy, which were closely related to memory impairment, especially CA1 atrophy and thalamic atrophy. More importantly, the volumes of some temporomesial regions and the MD values of WMH regions and NAWM may be potentially helpful neuroimaging indicators for distinguishing between SIVD-CI and SIVD-CU patients.

Altered Neurovascular Coupling in Subcortical Ischemic Vascular Disease.

Patients with subcortical ischemic vascular disease (SIVD) exhibit a high risk of cognitive impairment that might be caused by neurologic deficits and vascular injuries. However, the mechanism remains unknown. In current study, 24 normal controls (NC) and 54 SIVD patients, including 26 SIVD patients with no cognitive impairment (SIVD-NCI) and 28 SIVD patients with mild cognitive impairment (SIVD-MCI) underwent the resting-state functional MRI (rs-fMRI) and neuropsychological assessments. We combined regional homogeneity (ReHo) and cerebral blood flow (CBF) by using the global ReHo-CBF correlations coefficient and the ReHo/CBF ratio to detect the inner link between neuronal activity and vascular responses. Correlations between the ReHo/CBF ratio and neuropsychological assessments were explored in patients with SIVD. As a result, we identified significantly decreased global ReHo-CBF coupling in the SIVD-NCI group and SIVD- MCI group with respect to the NC. The SIVD-MCI group showed more serious decoupling of the global ReHo-CBF correlation. We also found a significantly abnormal ReHo/CBF ratio predominantly located in cognitive-related brain regions, including the left insula, right middle temporal gyrus, right precuneus, left precentral gyrus, and left inferior parietal lobule but not the supramarginal and angular gyri. The SIVD-MCI group showed more severe disorders of neurovascular coupling than the other two groups. Moreover, the ReHo/CBF ratio in the left precentral gyrus of the SIVD-NCI group exhibited a positive correlation with the MMSE scores. These findings suggested that patients with SIVD show abnormal neurovascular coupling at the early stage of the disease and during disease development. It might be associated with disease severity and cognitive impairment. Neurovascular decoupling in brain may be a possible neuropathological mechanism of SIVD.

Cortical Thinning in the Medial Temporal Lobe and Precuneus Is Related to Cognitive Deficits in Patients With Subcortical Ischemic Vascular Disease.

Subcortical ischemic vascular disease (SIVD) is a major cause of vascular cognitive impairment (CI) and features extensive atrophy in the cerebral cortex. We aimed to test the hypothesis that cognitive deficits in SIVD are linked to decreased cortical thickness in specific brain regions, which may constitute neuroimaging biomarkers of CI. Sixty-seven SIVD patients without (SIVD-NC, n = 35) and with (SIVD-CI, n = 32) CI and a group of healthy controls (HCs, n = 36) underwent structural magnetic resonance imaging (MRI) and cognitive functional assessments. FreeSurfer was used to preprocess structural MRI data and to calculate and compare cortical thickness. The correlation between cortical thickness and cognitive scores was examined in SIVD patients. Significantly altered cortical thickness in the bilateral insula, middle and inferior temporal lobes, precuneus, and medial temporal lobe (MTL) was identified among the three groups (p < 0.05, Monte Carlo simulation corrected). Post hoc results showed significantly decreased thickness in the bilateral insula and temporal lobe in SIVD-NC and SIVD-CI patients compared with HCs. However, the areas with reduced cortical thickness were larger in SIVD-CI than SIVD-NC patients. SIVD-CI patients had significantly reduced thickness in the bilateral precuneus and left MTL (Bonferroni corrected) compared with SIVD-NC patients when we extracted the mean thickness for each region of interest. In SIVD patients, the thicknesses of the left MTL and bilateral precuneus were positively correlated with immediate recall in the memory test. SIVD might lead to extensive cerebral cortical atrophy, while atrophy in the MTL and precuneus might be associated with memory deficits.

Changes in Gray Matter Asymmetries of the Fusiform and Parahippocampal Gyruses in Patients With Subcortical Ischemic Vascular Disease.

Objective: Changes in the normal asymmetry of the human brain often mean pathology. Current studies on the correlation between asymmetry and cognitive impairment have focused on Alzheimer's disease (AD) and AD-related mild cognitive impairment (MCI). The purpose of this study was to investigate changes in gray matter asymmetry and their relationship with cognitive impairment in patients with subcortical ischemic vascular disease (SIVD) by using voxel-based morphological measurements. Methods: Fifty-nine SIVD patients with (subcortical vascular cognitive impairment, SVCI, N = 30) and without (pre-SVCI, N = 29) cognitive impairment and 30 normal controls (NC, N = 30) underwent high-resolution structural MRI and neuropsychological examinations. The differences in gray matter asymmetry among the three groups were estimated by using one-way ANOVA. Moreover, partial correlation analysis was performed to explore the relationships between the asymmetry index (AI) values and cognitive assessments controlled for age, sex, and education. Results: The gray matter asymmetries in the fusiform and parahippocampal gyruses of the SVCI group were significantly different from those of the NC group and the pre-SVCI group, while no differences were found between the NC group and the pre-SVCI group in the same areas. More specifically, in the fusiform and parahippocampal gyruses, the SVCI group displayed a dramatic rightward asymmetry, whereas the NC group and pre-SVCI group exhibited a marked leftward asymmetry. The results of the correlation analysis showed that the "mean AI" in significant cluster was strongly correlated with the changes in cognitive outcomes. Conclusion: This study demonstrated different lateralization in the fusiform and parahippocampal gyruses of SIVD patients with cognitive impairment compared to healthy subjects and SIVD patients without cognitive decline. Our findings may contribute to better understanding the possible mechanism of cognitive impairment in patients with SIVD, and they suggest the possibility of using gray matter asymmetry as a biomarker for disease progression.

Alterations of White Matter Integrity in Subcortical Ischemic Vascular Disease with and Without Cognitive Impairment: a TBSS Study.

Patients with subcortical ischemic vascular disease (SIVD) may exhibit a high risk of cognitive impairment (CI) by disruption of white matter (WM) integrity. Diffusion tensor imaging (DTI) is recommended as a sensitive method to explore whole brain WM alterations at an asymptomatic stage of the disease, which might be correlated with underlying cognitive disorders. We aim to investigate alterations in WM microstructures and evaluate the relationships between the mean values of diffusion metrics (FA, MD, AD, and RD) and cognitive assessments in SIVD patients. Fifty SIVD patients with (SVCI, N = 25) and without (pre-SVCI, N = 25) cognitive impairments and normal controls (NC, N = 23) underwent DTI and neuropsychological examinations. DTI data were analyzed via TBSS to detect significant changes in WM tracts. Spearman correlation analysis was performed to evaluate relationships between the mean values of diffusion indices and the cognitive assessments. In general, extensive symmetrically altered areas that involved approximately the entire cerebral WM were noted in the pre-SVCI group but were less distinct than that noted in the SVCI group compared with NCs. The genu of corpus callosum exhibited the most damaged WM fiber. Throughout WM, FA was decreased, whereas MD, AD, and RD were increased. Some specific WM tracts in patient groups were significantly correlated with the severity of white matter hyperintensity (WMH), cognitive assessments about executive functions and processing speed. WM integrity has already been damaged at the pre-SVCI stage, which would be associate with future cognitive dysfunction. DTI could potentially establish early biomarkers to detect underlying mechanisms of SIVD.

Altered functional connectivity in patients with subcortical ischemic vascular disease: A resting-state fMRI study.

Patients with subcortical ischemic vascular disease (SIVD) may hold a high risk of cognitive impairment (CI) by affecting the functional connectivity (FC) of resting-state networks (RSNs). Current studies have mainly focused on the patients with CI but have ignored the prodromal stage when people suffered subcortical vascular damage, but without CI. Independent component analysis (ICA) of rs-fMRI could detect altered FC in RSNs at the early stage of the disease. 81 SIVD patients with CI (SVCI = 29) and without CI (pre-SVCI = 25), and 27 normal controls (NCs) were scanned with rs-fMRI, analyzed by ICA and assessed by neuropsychological examinations. We found significantly altered FC within the RSNs of sensorimotor network (SMN), posterior default mode networks (pDMN), right frontoparietal network (rFPN) and language network (LN) (P < 0.05, AlphaSim corrected). The pre-SVCI group showed significantly increased FC in brain regions of the multiple RSNs when compared with the other two groups. The mean values extracted from the right inferior frontal gyrus (IFG.R) and the left posterior cingulate gyrus (PCG.L) were significantly correlated with clock drawing test (CDT). The right precentral/postcentral gyrus (PreCG.R/PoCG.R) and the right supramarginal gyrus (SMG.R) were positively correlated with Stroop-1 Test. We concluded the FC in RSNs had already been changed at the early stage of the disease as the maladaptive response or compensatory reallocation of the cognitive resources. The ICA of rs-fMRI can be applied as a potential approach to identify the underlying mechanisms of SIVD.