Background/Aims: To investigate whether diffusion tensor imaging (DTI) is more sensitive than conventional MRI at detecting cognitive deterioration in patients with subcortical ischemic vascular disease (SIVD). Methods: Forty-two SIVD patients had a diagnosis of no cognitive impairment (NCI), vascular cognitive impairment/no dementia or vascular dementia (VaD). Whole-brain DTI histography and routine MRI were performed on these participants. Results: There were significant differences between cognitively impaired patients and NCI subjects in mean diffusivity and fractional anisotropy in either whole-brain white matter (WBWM) or in normal-appearing white matter (NAWM). All DTI indices within either WBWM or NAWM were found to be significantly correlated with both the attention-executive and memory measures in SIVD subjects. Lacune numbers and T₂-weighted lesions correlated only with attention-executive measures, whereas hippocampal volumes correlated only weakly with memory measures. Whole-brain gray matter volumes correlated with Z scores for all cognitive domains but language. After VaD patients had been excluded from the analysis, cognitive measures remained significantly correlated with some of the DTI indices, but not with conventional MRI findings. Conclusions: Compared with conventional MRI, whole-brain DTI is a more reliable and sensitive technique for the early detection of cognitive impairment in SIVD patients.

Objectives In this cross-sectional study, we aimed to explore the mechanisms of early cognitive impairment in a post stroke non-dementia cerebral small vessel disease (SVD) cohort by comparing the SVD score with the structural brain network measures. Method 127 SVD patients were recruited consecutively from a stroke clinic, comprising 76 individuals with mild cognitive impairment (MCI) and 51 with no cognitive impairment (NCI). Detailed neuropsychological assessments and multimodal MRI were performed. SVD scores were calculated on a standard scale, and structural brain network measures were analyzed by diffusion tensor imaging (DTI). Between-group differences were analyzed, and logistic regression was applied to determine the predictive value of SVD and network measures for cognitive status. Mediation analysis with structural equation modeling (SEM) was used to better understand the interactions of SVD burden, brain networks and cognitive deficits. Results Group difference was found on all global brain network measures. After adjustment for age, gender, education and depression, significant correlations were found between global brain network measures and diverse neuropsychological tests, including TMT-B ( r = −0.209, p < .05), DSST ( r = 0.206, p < .05), AVLT short term free recall ( r = 0.233, p < .05), AVLT long term free recall ( r = 0.264, p < .05) and Rey-O copy ( r = 0.272, p < .05). SVD score showed no group difference and was not correlated with cognition tests. Network global efficiency (E Global ) was significantly related to cognitive state ( p < .01) but not the SVD score. Mediation analysis showed that the standardized total effect ( p = .013) and the standardized indirect effect ( p = .016) of SVD score on cognition was significant, but the direct effect was not. Conclusions Brain network measures, but not the SVD score, are significantly correlated with cognition in post-stroke SVD patients. Mediation analysis showed that the cerebral vascular lesions produce cognitive dysfunction by interfering with the structural brain network in SVD patients. The brain network measures may be regarded as direct and independent surrogate markers of cognitive impairment in SVD.

Abnormal reductions in cortical cerebral blood flow (CBF) have been identified in subcortical vascular cognitive impairment (SVCI). However, little is known about the pattern of CBF reduction in relation with the degree of cognitive impairment. CBF measured with three-dimensional (3D) Arterial Spin Labeling (ASL) perfusion magnetic resonance imaging (MRI) helps detect functional changes in subjects with SVCI. We aimed to compare CBF maps in subcortical ischemic vascular disease (SIVD) subjects with and without cognitive impairment and to detect the relationship of the regions of CBF reduction in the brain with the degree of cognitive impairment according to the z-score. A total of 53 subjects with SVCI and 23 matched SIVD subjects without cognitive impairment (controls), underwent a whole-brain 3D ASL MRI in the resting state. Regional CBF (rCBF) was compared voxel wise by using an analysis of variance design in a statistical parametric mapping program, with patient age and sex as covariates. Correlations were calculated between the rCBF value in the whole brain and the z-score in the 53 subjects with SVCI. Compared with the control subjects, SVCI group demonstrated diffuse decreased CBF in the brain. Significant positive correlations were determined in the rCBF values in the left hippocampus, left superior temporal pole gyrus, right superior frontal orbital lobe, right medial frontal orbital lobe, right middle temporal lobe, left thalamus and right insula with the z-scores in SVCI group. The noninvasively quantified resting CBF demonstrated altered CBF distributions in the SVCI brain. The deficit brain perfusions in the temporal and frontal lobe, hippocampus, thalamus and insula was related to the degree of cognitive impairment. Its relationship to cognition indicates the clinical relevance of this functional marker. Thus, our results provide further evidence for the mechanisms underlying the cognitive deficit in patients with SVCI.

Background and Purpose: To assess the validity of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) in the detection of vascular mild cognitive impairment (VaMCI) in patients with subcortical ischemic vascular disease (SIVD). Methods: Among 102 SIVD patients, both cutoff scores of the MMSE and MoCA for differentiating VaMCI from no cognitive impairment (NCI) or differentiating VaMCI from vascular dementia (VaD) were determined by the receiver operator characteristic (ROC) analysis. Optimal sensitivity with specificity of cutoff scores was obtained after the raw scores were adjusted for education. Results: After adjusting for education, the MoCA cutoff score for differentiating VaMCI from NCI was at 24/25 and that for differentiating VaMCI from VaD was at 18/19. After applying the adjusted MoCA scores from 19 to 24 to identify VaMCI in all SIVD patients, sensitivity was at 76.7% and specificity was at 81.4% (κ = 0.579). The adjusted cutoff score of the MMSE for differentiating VaMCI from NCI was at 28/29 and that for differentiating VaMCI from VaD was at 25/26. The sensitivity and specificity of the adjusted MMSE was at 58.1 and 71.2%, respectively, when using the score from 26 to 28 to identify VaMCI in SIVD patients (κ = 0.294). Conclusions: The MoCA detected subcortical VaMCI better than the MMSE.

The presence and pattern of iron accumulation in subcortical vascular mild cognitive impairment (svMCI) and their effects on cognition have rarely been investigated. We aimed to examine brain iron deposition in svMCI subjects using quantitative susceptibility mapping (QSM). Moreover, we aimed to investigate the correlation between brain iron deposition and the severity of cognitive impairment as indicated by z-scores. We recruited 20 subcortical ischemic vascular disease (SIVD) patients who fulfilled the criteria for svMCI. The control group comprised 19 SIVD patients without cognitive impairment. The SIVD and control groups were matched based on age, gender, and years of education. Both groups underwent QSM using a 3.0T MRI system. Susceptibility maps were reconstructed from in vivo data, which were acquired with a three-dimensional spoiled gradient recalled sequence. Then, regions of interest were drawn manually on the map of each subject. The inter-group differences of susceptibility values were explored in deep gray matter nuclei, including the bilateral pulvinar nucleus of the thalamus, head of caudate nucleus, globus pallidus, putamen, hippocampus, substantia nigra, and red nucleus. The correlations between regional iron deposition and composite z-score, memory z-score, language z-score, attention-executive z-score and visuospatial z-score were assessed using partial correlation analysis, with patient age and gender as covariates. Compared with the control, the svMCI group had elevated susceptibility values within the bilateral hippocampus and right putamen. Furthermore, the susceptibility value in the right hippocampus was negatively correlated with memory z-score and positively correlated with language z-score. The susceptibility value in the right putamen was negatively correlated with attention-executive z-score in the svMCI group. However, composite z-score were unrelated to susceptibility values. Our results suggest that brain iron deposition has clinical relevance as a biomarker for cognition. In addition, our results highlight the importance of iron deposition in understanding svMCI-associated cognitive deficits in addition to conventional MRI markers.

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We conducted a cross-sectional study to characterize the relationship between total and modified small vessel disease (SVD) score with vascular cognitive impairment (VCI). Patients (n = 157) between the ages of 50 and 85 years old who had suffered their first lacunar infarction were analyzed prospectively. Brain magnetic resonance imaging was performed to identify SVD manifestations, which were used to calculate total or modified SVD scores. Neuropsychological assessments measured cognitive function. Spearman correlation analysis demonstrated that the total and modified SVD scores were associated with overall cognition as well as with function in the executive and visuospatial domains. The associations remained significant in linear regression after adjusting for age, sex, education and vascular risk factors. Binary logistic regression and chi-squared trend tests revealed that VCI risk increased significantly with SVD burden based on the modified SVD score. Subsequent chi-squared testing demonstrated that the VCI rate was significantly higher in patients with a modified SVD score of 5-6 than in patients without any SVD burden. Our results suggest that both the total and modified SVD scores show a negative association with cognitive function, but the modified SVD score may be better at identifying patients at high VCI risk.

Recent neuroimaging studies have shown that people with subcortical vascular cognitive impairment (sVCI) have structural and functional abnormalities in the frontal lobe and subcortical brain sites. In this study, we used seed-based resting-state functional connectivity (rsFC) analysis and voxel-mirrored homotopic connectivity (VMHC) techniques to investigate the alteration of rsFC in patients with sVCI. rsFC and structural magnetic resonance images were acquired for 51 patients with subcortical cerebrovascular disease. All patients were subdivided based on cognitive status into 29 with sVCI and 22 controls; patient characteristics were matched. rsFC of the posterior cingulate cortex (PCC) and VMHC were calculated separately, and rsFC of the PCC and VMHC between the two groups were compared. The regions showing abnormal rsFC of the PCC or VMHC in sVCI patients were adopted as regions of interest for correlation analyses. Our results are as follows: The patients with sVCI exhibited increases in rsFC in the left middle temporal lobe, right inferior temporal lobe and left superior frontal gyrus, and significant decreases in rsFC of the left thalamus with the PCC. sVCI patients showed a significant deficit in VMHC between the bilateral lingual gyrus, putamen, and precentral gyrus. Additionally, the z-memory score was significantly positively associated with connectivity between the left thalamus and the PCC (r = 0.41, p = 0.03, uncorrected) in the sVCI group. Our findings suggest that the frontal lobe and subcortical brain sites play an important role in the pathogenesis of sVCI. Furthermore, rsFC between the left thalamus and the PCC might indicate the severity of sVCI.