scholarly journals Heterogeneity of White Matter Hyperintensities in Cognitively Impaired Patients With Cerebral Small Vessel Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingting Wang ◽  
Aoming Jin ◽  
Ying Fu ◽  
Zaiqiang Zhang ◽  
Shaowu Li ◽  
...  

ObjectiveSimilar white matter hyperintensities (WMH) might have different impact on the cognitive outcomes in patients with cerebral small vessel disease (CSVD). This study is to assess the possible factors related to the heterogeneity of WMH in cognitively impaired patients with CVSD.MethodsWe analyzed data from a cohort of patients with CVSD who were recruited consecutively from the Beijing Tiantan Hospital from 2015 to 2020. WMH, lacunes, enlarged perivascular space (ePVS), microbleeds and lacunar infarcts were rated on brain MRI. A score of <26 on the Montreal Cognitive Assessment (MoCA) indicated cognitive impairment. A mismatch was defined as the severity of WMH not matching the severity of cognitive dysfunction. Type-1 mismatch was defined as a mild WMH (Fazekas score = 0-1) associated with cognitive impairment, and type-2 mismatch was defined as a severe WMH (Fazekas score = 5-6) associated with normal cognitive function. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced SWI on 3-Tesla MRI was used to image the penetrating arteries in basal ganglia to explore the underlying mechanism of this mismatch. Multivariable logistic regression was used to analyze the association between the imaging features and cognitive impairment.ResultsIn 156 patients, 118 (75.6%) had cognitive impairment and 37 (23.7%) showed mismatch. Twenty five (16.0%) had type-1 mismatch and 12 (7.7%) had type-2 mismatch. Regression analysis found that WMH, lacunes, microbleeds and total CSVD scores were associated with cognitive impairment and were independent of vascular risk factors. However, lacunes, microbleeds and total CSVD scores were related to the mismatch between WMH and cognitive impairment (p=0.006, 0.005 and 0.0001, respectively). Specially, age and ePVS in basal ganglia were related to type-1 mismatch (p=0.04 and 0.02, respectively); microbleeds and total CSVD scores were related to type-2 mismatch (p=0.01 and 0.03, respectively). Although the severity of WMH was similar, the injury scores of penetrating arteries were significantly different between those with and without cognitive impairment (p=0.04).ConclusionsHeterogeneity of WMH was present in cognitively impaired patients with CSVD. Conventional imaging features and injury of penetrating arteries may account for such heterogeneity, which can be a hallmark for early identification and prevention of cognitive impairment.

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 479-484
Author(s):  
Tatjana Bošković Matić ◽  
Gordana Toncev ◽  
Aleksandar Gavrilović ◽  
Dejan Aleksić

AbstractBackgroundCerebral small vessel disease (CSVD) and metabolic syndrome were separately associated with cognitive impairment and depression. However, whether metabolic syndrome adds to cognitive impairment and depression in patients who already have CSVD remained unanswered.ObjectiveThe aim of our study was to investigate the association of metabolic syndrome with cognitive impairment and depression in patients with CSVD who have lacunar lesions or white matter hyperintensities.MethodsThis prospective cohort study was conducted at Neurology Clinic, Clinical Center, Kragujevac, Serbia. Main outcomes of the study were cognitive assessment, and assessment of depression among hospitalized patients with or without CSVD.ResultsThe study included 74 inpatients, 25 of them having lacunary infarctions, 24 with the white matter hyperintensities, and 25 control patients without CSVD. The CSVD was accompanied by impairment of cognition and depression, the patients with lacunary lesions being more cognitively impaired and more depressive than the patients with the white matter hyperintensities. The patients with CSVD who also had metabolic syndrome were more cognitively impaired and depressed than the patients with CSVD alone.ConclusionsIn conclusion, our study showed that metabolic syndrome is associated with further worsening of already impaired cognition and existing depression in patients with CSVD.


Diagnostics ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 354 ◽  
Author(s):  
Larisa A. Dobrynina ◽  
Maryam R. Zabitova ◽  
Alla A. Shabalina ◽  
Elena I. Kremneva ◽  
Bulat M. Akhmetzyanov ◽  
...  

The evaluation of the clustering of magnetic resonance imaging (MRI) signs into MRI types and their relationship with circulating markers of vascular wall damage were performed in 96 patients with cerebral small vessel disease (cSVD) (31 men and 65 women; mean age, 60.91 ± 6.57 years). The serum concentrations of the tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), and hypoxia-inducible factor 1-α (HIF-1α) were investigated in 70 patients with Fazekas stages 2 and 3 of white matter hyperintensities (WMH) and 21 age- and sex-matched volunteers with normal brain MRI using ELISA. The cluster analysis excluded two patients from the further analysis due to restrictions in their scanning protocol. MRI signs of 94 patients were distributed into two clusters. In the first group there were 18 patients with Fazekas 3 stage WMH. The second group consisted of 76 patients with WMH of different stages. The uneven distribution of patients between clusters limited the subsequent steps of statistical analysis; therefore, a cluster comparison was performed in patients with Fazekas stage 3 WMH, designated as MRI type 1 and type 2 of Fazekas 3 stage. There were no differences in age, sex, degree of hypertension, or other risk factors. MRI type 1 had significantly more widespread WMH, lacunes in many areas, microbleeds, atrophy, severe cognitive and gait impairments, and was associated with downregulation of VEGF-A compared with MRI type 2. MRI type 2 had more severe deep WMH, lacunes in the white matter, no microbleeds or atrophy, and less severe clinical manifestations and was associated with upregulation of TNF-α compared with MRI type 1. The established differences reflect the pathogenetic heterogeneity of cSVD and explain the variations in the clinical manifestations observed in Fazekas stage 3 of this disease.


2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Fanny Quandt ◽  
Felix Fischer ◽  
Julian Schröder ◽  
Marlene Heinze ◽  
Iris Lettow ◽  
...  

Abstract Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging is white matter hyperintensities. We studied high-resolution resting-state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment; however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioural impairment.


Stroke ◽  
2019 ◽  
Vol 50 (12) ◽  
pp. 3540-3544 ◽  
Author(s):  
Eline A. Oudeman ◽  
Jacoba P. Greving ◽  
Renske M. Van den Berg-Vos ◽  
Geert Jan Biessels ◽  
Esther E. Bron ◽  
...  

Background and Purpose— Nonfocal transient neurological attacks (TNAs), such as unsteadiness, bilateral weakness, or confusion, are associated with an increased risk of stroke and dementia. Cerebral ischemia plays a role in their pathogenesis, but the precise mechanisms are unknown. We hypothesized that cerebral small vessel disease is involved in the pathogenesis of TNAs and assessed the relation between TNAs and manifestations of cerebral small vessel disease on magnetic resonance imaging. Methods— We included participants from the HBC (Heart-Brain Connection) study. In this study, hemodynamic and cardiovascular contributions to cognitive impairment have been studied in patients with heart failure, carotid artery occlusion, or possible vascular cognitive impairment, as well as in a reference group. We excluded participants with a history of stroke or transient ischemic attacks. The occurrence of the following 8 TNAs was assessed with a standardized interview: unconsciousness, confusion, amnesia, unsteadiness, bilateral leg weakness, blurred vision, nonrotatory dizziness, and paresthesias. The occurrence of TNAs was related to the presence of lacunes or white matter hyperintensities (Fazekas score, ≥2; early confluent or confluent lesions) in logistic regression analysis, adjusted for age, sex, and hypertension. Results— Of 304 participants (60% men; mean age, 67±9 years), 63 participants (21%) experienced ≥1 TNAs. Lacunes and early confluent or confluent white matter hyperintensities were more common in participants with TNAs than in participants without TNAs (35% versus 20%; adjusted odds ratio, 2.32 [95% CI, 1.22–4.40] and 48% versus 27%; adjusted odds ratio, 2.65 [95% CI, 1.44–4.90], respectively). Conclusions— In our study, TNAs are associated with the presence of lacunes and early confluent or confluent white matter hyperintensities of presumed vascular origin, which indicates that cerebral small vessel disease might play a role in the pathogenesis of TNAs.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xiaoping Tang ◽  
Xinlan Xiao ◽  
Jianhua Yin ◽  
Ting Yang ◽  
Bingliang Zeng

In order to assess the relationship between structural and functional imaging of cerebrovascular disease and cognition-related fibers, this paper chooses a total of 120 patients who underwent cerebral small vessel disease (CSVD) treatment at a designated hospital by this study from June 2013 to June 2018 and divides them into 3 groups according to the random number table method: vascular dementia (VaD) group, vascular cognitive impairment no dementia (VCIND) group, and noncognition impairment (NCI) group with 40 cases of patients in each group. Cognitive function measurement and imaging examination were performed for these 3 groups of patients, and the observation indicators of cognitive state examination (CSE), mental assessment scale (MAS), clock drawing test (CDT), adult intelligence scale (AIS), frontal assessment battery (FAB), verbal fluency test (VFT), trail making test (TMT), cognitive index (CI), white matter lesions (WML), third ventricle width (TVW), and frontal horn index (FHI) were tested, respectively. The results shows that the average scores of CSE, MAS, AIS, and VFT in the VaD and VCIND group are lower than those of the NCI group and the differences are statistically significant (P<0.05); the average scores of FAB, TMT, and CI in the VaD group are higher than those of the VCIND group and the differences are also statistically significant (P<0.05); the average scores of FHI and TVW in the VaD group are lower than those of the VCIND and NCI group with statistically significant differences (P<0.05); the average scores of WML, CDT, and AIS in the VaD group are higher than those of the VCIND and NCI group with statistically significant differences (P<0.05). Therefore, it is believed that the structural and functional imaging features of cerebrovascular disease are closely related to cognition-related fibers, and the incidence of white matter lesions is closely related to the degree of lesions and cognitive dysfunction of cerebral small vessel disease, in which a major risk factor for cognitive dysfunction in patients with small blood vessels is the severity of white matter lesions; brain imaging and neuropsychiatric function assessment can better understand the relationship between cerebrovascular disease and cognitive impairment. The results of this study provide a reference for the further research studies on the relationship between structural and functional imaging of cerebrovascular disease and cognition-related fibers.


Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 720
Author(s):  
Larisa A. Dobrynina ◽  
Zukhra Sh. Gadzhieva ◽  
Kamila V. Shamtieva ◽  
Elena I. Kremneva ◽  
Bulat M. Akhmetzyanov ◽  
...  

Introduction: Cerebral small vessel disease (CSVD) is the leading cause of vascular and mixed degenerative cognitive impairment (CI). The variability in the rate of progression of CSVD justifies the search for sensitive predictors of CI. Materials: A total of 74 patients (48 women, average age 60.6 ± 6.9 years) with CSVD and CI of varying severity were examined using 3T MRI. The results of diffusion tensor imaging with a region of interest (ROI) analysis were used to construct a predictive model of CI using binary logistic regression, while phase-contrast magnetic resonance imaging and voxel-based morphometry were used to clarify the conditions for the formation of CI predictors. Results: According to the constructed model, the predictors of CI are axial diffusivity (AD) of the posterior frontal periventricular normal-appearing white matter (pvNAWM), right middle cingulum bundle (CB), and mid-posterior corpus callosum (CC). These predictors showed a significant correlation with the volume of white matter hyperintensity; arterial and venous blood flow, pulsatility index, and aqueduct cerebrospinal fluid (CSF) flow; and surface area of the aqueduct, volume of the lateral ventricles and CSF, and gray matter volume. Conclusion: Disturbances in the AD of pvNAWM, CB, and CC, associated with axonal damage, are a predominant factor in the development of CI in CSVD. The relationship between AD predictors and both blood flow and CSF flow indicates a disturbance in their relationship, while their location near the floor of the lateral ventricle and their link with indicators of internal atrophy, CSF volume, and aqueduct CSF flow suggest the importance of transependymal CSF transudation when these regions are damaged.


2018 ◽  
Vol 4 (1) ◽  
pp. 85-89 ◽  
Author(s):  
Esther MC van Leijsen ◽  
Mayra I Bergkamp ◽  
Ingeborg WM van Uden ◽  
Sjacky Cooijmans ◽  
Mohsen Ghafoorian ◽  
...  

Introduction Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers. Patients and methods Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessments at three time-points over 8.7 years. We semi-automatically assessed white matter hyperintensities volumes and manually rated lacunes and microbleeds. We analysed differences in cognitive decline and accompanying brain atrophy between participants with regression, progression and stable small vessel disease by analysis of variance. Results Fifty-six participants (20.3%) showed regression of small vessel disease markers: 31 (11.2%) white matter hyperintensities regression, 10 (3.6%) vanishing lacunes and 27 (9.8%) vanishing microbleeds. Participants with regression showed a decline in overall cognition, memory, psychomotor speed and executive function similar to stable small vessel disease. Participants with small vessel disease progression showed more cognitive decline compared with stable small vessel disease (p < 0.001 for cognitive index and memory; p < 0.01 for executive function), although significance disappeared after adjusting for age and sex. Loss of total brain, gray matter and white matter volume did not differ between participants with small vessel disease regression and stable small vessel disease, while participants with small vessel disease progression showed more volume loss of total brain and gray matter compared to those with stable small vessel disease (p < 0.05), although significance disappeared after adjustments. Discussion Regression of small vessel disease markers was associated with similar cognitive decline compared to stable small vessel disease and did not accompany brain atrophy, suggesting that small vessel disease regression follows a relatively benign clinical course. Future studies are required to validate these findings and to assess the role of vascular risk factor control on small vessel disease regression and possible recovery of clinical symptoms. Conclusion Our findings of comparable cognitive decline between participants with regression and stable small vessel disease might suggest that small vessel disease regression has a relative benign cognitive outcome.


Stroke ◽  
2020 ◽  
Vol 51 (5) ◽  
pp. 1404-1410 ◽  
Author(s):  
Michelle P. Lin ◽  
Thomas G. Brott ◽  
David S. Liebeskind ◽  
James F. Meschia ◽  
Kevin Sam ◽  
...  

Background and Purpose— Cerebral small vessel disease (SVD) is associated with increased stroke risk and poor stroke outcomes. We aimed to evaluate whether chronic SVD burden is associated with poor recruitment of collaterals in large-vessel occlusive stroke. Methods— Consecutive patients with middle cerebral artery or internal carotid artery occlusion presenting within 6 hours after stroke symptom onset who underwent thrombectomy from 2012 to 2017 were included. The prespecified primary outcome was poor collateral flow, which was assessed on baseline computed tomographic angiography (poor, ≤50% filling; good, >50% filling). Markers of chronic SVD on brain magnetic resonance imaging were rated for the extent of white matter hyperintensities, enlarged perivascular spaces, chronic lacunar infarctions and cerebral microbleeds using the Standards for Reporting Vascular Changes on Neuroimaging criteria. Severity of SVD was quantified by adding the presence of each SVD feature, with a total possible score of 0 to 4; each SVD type was also evaluated separately. Multivariable logistic regression analyses were performed to evaluate the relationships between SVD and poor collaterals, with adjustment for potential confounders. Results— Of the 100 eligible patients, the mean age was 65±16 years, median National Institutes of Health Stroke Scale score was 15, and 68% had any SVD. Poor collaterals were observed in 46%, and those with SVD were more likely to have poor collaterals than patients without SVD (aOR, 1.9 [95% CI, 1.1–3.2]). Of the SVD types, poor collaterals were significantly associated with white matter hyperintensities (aOR, 2.9 per Fazekas increment [95% CI, 1.6–5.3]) but not with enlarged perivascular spaces (adjusted odds ratio [aOR], 1.3 [95% CI, 0.4–4.0]), lacunae (aOR, 2.1 [95% CI, 0.6–7.1]), or cerebral microbleeds (aOR, 2.1 [95% CI, 0.6–7.8]). Having a greater number of different SVD markers was associated with a higher odds of poor collaterals (crude trend P <0.001; adjusted P =0.056). There was a dose-dependent relationship between white matter hyperintensity burden and poor collaterals: adjusted odds of poor collaterals were 1.5, 3.0, and 9.7 across Fazekas scores of 1 to 3 ( P trend=0.015). No patient with an SVD score of 4 had good collaterals. Conclusions— Chronic cerebral SVD is associated with poor recruitment of collaterals in large vessel occlusive stroke. A prospective study to elucidate the potential mechanism of how SVD may impair the recruitment of collaterals is ongoing.


2019 ◽  
Vol 15 (6) ◽  
pp. 657-665 ◽  
Author(s):  
Jun Yoshida ◽  
Fumio Yamashita ◽  
Makoto Sasaki ◽  
Kunihiro Yoshioka ◽  
Shunrou Fujiwara ◽  
...  

Background Although patients with improved cognition after carotid endarterectomy usually exhibit postoperative restoration of cerebral blood flow, less than half of patients with such cerebral blood flow change have postoperatively improved cognition. Cerebral small vessel disease on magnetic resonance imaging is associated with irreversible cognitive impairment. Aims The purpose of the present prospective study was to determine whether pre-existing cerebral small vessel disease affects cognitive improvement after carotid endarterectomy. Methods Brain MR imaging was performed preoperatively, and the number or grade of each cerebral small vessel disease was determined in 80 patients undergoing carotid endarterectomy for ipsilateral internal carotid artery stenosis (≥70%). The volume of white matter hyperintensities relative to the intracranial volume was also calculated. Brain perfusion single-photon emission computed tomography and neuropsychological testing were performed preoperatively and two months postoperatively. Based on these data, a postoperative increase in cerebral blood flow and postoperative improved cognition, respectively, were determined. Results Logistic regression analysis using the sequential backward elimination approach revealed that a postoperative increase in cerebral blood flow (95% confidence interval [CI], 10.74–3730.00; P = 0.0004) and the relative volume of white matter hyperintensities (95% CI, 0.01–0.63; P = 0.0314) were significantly associated with postoperative improved cognition. Although eight of nine patients with postoperative improved cognition exhibited both a relative volume of white matter hyperintensities <0.65% and a postoperative increase in cerebral blood flow, none of patients with a relative volume of white matter hyperintensities ≥0.65% had postoperative improved cognition regardless of any postoperative change in cerebral blood flow. Conclusion Pre-existing cerebral white matter hyperintensities on magnetic resonance imaging adversely affect cognitive improvement after carotid endarterectomy.


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