UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

OBJECTIVE: To explore the static and dynamic characteristics of intrinsic brain activity (IBA) in subcortical ischemic vascular disease (SIVD) patients with or without cognitive impairment.
METHODS: In total, 90 participants were recruited, including 32 SIVD patients with cognitive impairment (SIVD-CI, N = 32), 26 SIVD patients with no cognitive impairment (SIVD-NCI, N = 26), and 32 healthy controls (HC, N = 32) matched for age, gender, and education. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and neuropsychological tests. Amplitude of low-frequency fluctuation (ALFF) was calculated to reflect static alterations of regional IBA. Sliding window analysis was conducted in order to explore the dynamic characteristics.
RESULTS: Both SIVD-CI and SIVD-NCI group showed significantly decreased ALFF in left angular gyrus (ANG), whereas SIVD-CI group showed increased ALFF in right superior frontal gyrus (SFG), compared with HCs. Furthermore, SIVD-CI group showed significantly decreased ALFF dynamics (dALFF) in right precuneus (PreCu) and left dorsal anterior cingulate cortex (dACC), compared with HC and SIVD-NCI groups (Gaussian random field-corrected, voxel-level P < 0.001, cluster-level P < 0.05). No dynamic changes were detected between SIVD-NCI group and HC group. The mean ALFF value in left ANG of SIVD-CI group was correlated with the score of delayed memory scale.
CONCLUSIONS: ANG may be a vulnerable brain region in SIVD patients. Temporal dynamic analysis could serve as a sensitive and promising method to investigate IBA alterations in SIVD patients.

It is challenging to predict which patients who meet criteria for subcortical ischemic vascular disease (SIVD) will ultimately progress to subcortical vascular cognitive impairment (SVCI).
We collected clinical information, neuropsychological assessments, T1 imaging, diffusion tensor imaging, and resting-state functional magnetic resonance imaging from 83 patients with SVCI and 53 age-matched patients with SIVD without cognitive impairment. We built an unsupervised machine learning model to isolate patients with SVCI. The model was validated using multimodal data from an external cohort comprising 45 patients with SVCI and 32 patients with SIVD without cognitive impairment.
The accuracy, sensitivity, and specificity of the unsupervised machine learning model were 86.03%, 79.52%, and 96.23% and 80.52%, 71.11%, and 93.75% for internal and external cohort, respectively.
We developed an accurate and accessible clinical tool which requires only data from routine imaging to predict patients at risk of progressing from SIVD to SVCI.
Our unsupervised machine learning model provides an accurate and accessible clinical tool to predict patients at risk of progressing from subcortical ischemic vascular disease (SIVD) to subcortical vascular cognitive impairment (SVCI) and requires only data from imaging routinely used during the diagnosis of suspected SVCI. The model yields good accuracy, sensitivity, and specificity and is portable to other cohorts and to clinical practice to distinguish patients with SIVD at risk for progressing to SVCI. The model combines assessment of diffusion tensor imaging and functional magnetic resonance imaging measures in patients with SVCI to analyze whether the \"disconnection hypothesis\" contributes to functional and structural changes and to the clinical presentation of SVCI.

Alterations in the temporal evolution of brain states in the process of cognitive impairment aggravation due to subcortical ischemic vascular disease (SIVD) is not understood. The dynamic functional connectivity was investigated to identify the abnormal temporal properties of brain states associated with cognitive impairment caused by SIVD. Eighteen patients with subcortical ischemic vascular cognitive impairment with no dementia (SIVCIND), 19 dementia patients (SIVaD) and 26 normal controls were enrolled. We found that the occupancy rate and mean lifetime of brain states were associated with cognitive performance. SIVCIND had a higher occupancy rate and longer mean lifetime in weakly connected states than normal controls. SIVaD had similar but more extensive changes in the temporal properties of brain states. In addition, switching from weakly connected states to more strongly connected states was more difficult in SIVCIND and SIVaD patients than in normal controls, especially in SIVaD patients. The results revealed that not only the transition to but also maintenance in strongly connected states became increasingly difficult when SIVD-related cognitive impairment progressed into a more severe stage.

Subcortical ischemic vascular disease (SIVD) is one of the important causes of cognitive dysfunction, altered amyloid-beta (Aβ) and cerebral perfusion may be involved in the pathophysiological mechanism of SIVD and are closely related to cognitive function. We aimed to investigate altered serum Aβ and cerebral perfusion in patients with SIVD and their correlation with cognitive function. Seventy-four healthy controls (HCs) and 74 SIVD patients, including 38 SIVD patients with no cognitive impairment (SIVD-NCI) and 36 SIVD patients with mild cognitive impairment (SIVD-MCI) underwent the measurement of serum Aβ40 and Aβ42 levels, pseudo-continuous arterial spin labeling MRI scanning, and cognitive evaluation. Compared to the healthy controls (HCs), the level of serum Aβ40 and Aβ40/42 ratio increased and Aβ42 decreased in SIVD patients. The serum Aβ40 level and Aβ40/42 ratio in patients with SIVD-MCI were significantly higher than those in the HCs and SIVD-NCI, and the level of Aβ42 in the SIVD-MCI was lower than the HCs. In addition, the serum Aβ40/42 ratio provided high diagnostic accuracy for SIVD and SIVD-MCI, it was further identified as an independent risk factor for cognitive impairment. Patients with SIVD-NCI and SIVD-MCI exhibited both increased and decreased cerebral blood flow (CBF) in regional. The Aβ40/42 ratio was associated with global CBF, while altered global and regional CBF was associated with cognitive deficits. In addition, white matter hyperintensities volume (WMHV) correlated with Aβ40/42 ratio, CBF, and cognition. The relationship between Aβ40/42 ratio and cognition was partially mediated by altered CBF. Based on these results, we conclude that the serum Aβ40/42 ratio may be a potential biomarker that can complement current methods for the prediction and diagnosis of cognitive impairment in SIVD patients. In addition, serum Aβ may play a role in cognitive function by regulating CBF, which provides new insights into the intervention, treatment, and prevention of cognitive impairment in SIVD.

UNASSIGNED: Subcortical ischemic vascular disease (SIVD) is a leading cause of vascular dementia. The present study tries to explore not only the gender-specific association between H-type hypertension and SIVD but also the indirect effects of H-type hypertension on cognition through the ischemic brain injury caused by SIVD.
UNASSIGNED: A total of 601 SIVD patients were included, comprising 322 males and 279 females. H-type hypertension was defined as hypertension accompanied with elevated serum total homocysteine (tHcy) level. The imaging manifestations of ischemic brain injury caused by SIVD were also evaluated, including white matter lesions (WML), lacunar infarction (LI) and brain atrophy (BA). Gender-specific subgroup analyses in association between H-type hypertension and SIVD were conducted, followed by a structural equation model based evaluation of the gender-specific mediating effects of SIVD on the relationship between H-type hypertension and cognition.
UNASSIGNED: For males, there was no noticeable difference in WML, LI and BA scores among control group, isolated hypertension group, isolated high tHcy group, and H-type hypertension group in most brain regions, but significant difference was found in all brain regions for females. Multiple regression analyses showed that H-type hypertension was significantly associated with WML, LI and BA for females, but not for males. For males, H-type hypertension mainly affected cognition through direct effect, while the H-type hypertension effect was mediated by ischemic brain injury caused by SIVD for females.
UNASSIGNED: H-type hypertension was more closely related to SIVD for females than males, suggesting a gender-specific difference in association patterns between H-type hypertension and cognition.

UNASSIGNED: Patients with subcortical ischemic vascular disease (SIVD) suffer from memory disorders that are thought to be associated with the hippocampus. We aimed to explore changes in hippocampal subfields and the relationship between different hippocampal subfield volumes and different types of memory dysfunction in SIVD patients.
UNASSIGNED: A total of 77 SIVD patients with cognitive impairment (SIVD-CI, n = 39) or normal cognition (HC-SIVD, n = 38) and 41 matched healthy controls (HCs) were included in this study. Memory function was measured in all subjects, and structural magnetic resonance imaging (MRI) was performed. Then, the hippocampus was segmented and measured by FreeSurfer 6.0 software. One-way ANOVA was used to compare the volume of hippocampal subfields among the three groups while controlling for age, sex, education and intracranial volume (ICV). Then, post hoc tests were used to evaluate differences between each pair of groups. Finally, correlations between significantly different hippocampal subfield volumes and memory scores were tested in SIVD patients.
UNASSIGNED: Almost all hippocampal subfields were significantly different among the three groups except for the bilateral hippocampal fissure (p = 0.366, p = 0.086, respectively.) and left parasubiculum (p = 0.166). Furthermore, the SIVD-CI patients showed smaller volumes in the right subiculum (p < 0.001), CA1 (p = 0.002), presubiculum (p = 0.002) and molecular layer of the hippocampus (p = 0.017) than the HC-SIVD patients. In addition, right subiculum volumes were positively related to Rey\'s Auditory Verbal Learning Test (RAVLT) word recognition (r = 0.230, p = 0.050), reverse digit span test (R-DST) (r = 0.326, p = 0.005) and Rey-Osterrieth Complex Figure Test (ROCF) immediate recall (r = 0.247, p = 0.035) scores, right CA1 volumes were positively correlated with RAVLT word recognition (r = 0.261, p = 0.026), and right presubiculum volumes showed positive relationships with R-DST (r = 0.254, p = 0.030) and ROCF immediate recall (r = 0.242, p = 0.039) scores.
UNASSIGNED: SIVD might lead to general reductions in volume in multiple hippocampal subfields. However, SIVD-CI patients showed atrophy in specific subfields, which might be associated with memory deficits.

Few studies have investigated differences in functional connectivity (FC) between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer\'s disease (AD), especially in relation to apathy. Therefore, the aim of this study was to compare apathy-related FC changes among patients with SIVD, AD, and cognitively normal subjects. The SIVD group had the highest level of apathy as measured using the Apathy Evaluation Scale-clinician version (AES). Dementia staging, volume of white matter hyperintensities (WMH), and the Beck Depression Inventory were the most significant clinical predictors for apathy. Group-wise comparisons revealed that the SIVD patients had the worst level of \"Initiation\" by factor analysis of the AES. FCs from four resting state networks (RSNs) were compared, and the connectograms at the level of intra- and inter-RSNs revealed dissociable FC changes, shared FC in the dorsal attention network, and distinct FC in the salient network across SIVD and AD. Neuronal correlates for \"Initiation\" deficits that underlie apathy were explored through a regional-specific approach, which showed that the right inferior frontal gyrus, left middle frontal gyrus, and left anterior insula were the critical hubs. These findings broaden the disconnection theory by considering the effect of FC interactions across multiple RSNs on apathy formation.

OBJECTIVE: 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.
CONCLUSIONS: 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.

Subcortical ischemic vascular disease (SIVD) can cause cognitive impairment and affect the static functional connectivity of resting functional magnetic resonance imaging (fMRI). Numerous previous studies have demonstrated that functional connectivities (FCs) fluctuate dynamically over time. However, little is known about the impact of cognitive impairment on brain dynamic functional connectivity (DFC) in SIVD patients with MCI. In the present study, the DFC analysis method was applied to the resting functional magnetic resonance imaging (fMRI) data of 37 SIVD controls (SIVD-Control) without cognitive impairment, 34 SIVD patients with amnestic MCI (SIVD-aMCI) and 30 SIVD patients with nonamnestic MCI (SIVD-naMCI). The results indicated that the cognitive impairment of SIVD mainly reduced the mean dwell time of State 3 with overall strong positive connections. The reduction degree of SIVD-aMCI was larger than that of SIVD-naMCI. The memory/execution function impairment of SIVD also changed the relationship between the mean dwell time of State 3 and the behavioral performance of the memory/execution task from significant to non-significant correlation. Moreover, SIVD-aMCI showed significantly lower system segregation of FC states than SIVD-Control and SIVD-naMCI. The system segregation of State 5 with overall weak connections was significantly positive correlated with the memory performance. The results may suggest that the mean dwell time of State 3 and the system segregation of State 5 may be used as important neural measures of cognitive impairments of SIVD.