Rich-Club Analysis of the Structural Brain Network in Cases with Cerebral Small Vessel Disease and Depression Symptoms

2021 ◽  
pp. 1-10
Author(s):  
Yanjing Lu ◽  
Yifan Li ◽  
Qian Feng ◽  
Rong Shen ◽  
Hao Zhu ◽  
...  

<b><i>Background:</i></b> Altered white matter brain networks have been extensively studied in cerebral small vessel disease (SVD). However, there exists currently a deficiency of comprehending the performance of changes within the structural networks of the brain in cases with cerebral SVD and depression symptoms. The main aim of the present research is to study the network topology behaviors and features of rich-club organization in SVD patients using graph theory and diffusion tensor imaging (DTI) to characterize changes in the microstructure of the brain. <b><i>Methods:</i></b> DTI datasets were acquired from 26 SVD patients with symptoms of depression (SVD + D) and 26 SVD patients without symptoms of depression (SVD − D), and a series of neuropsychological assessments were completed. A structural network was created using a deterministic fiber tracking method. The analysis of rich-club was performed in company with analysis of the global network features of the network to characterize the topological properties of all subjects. <b><i>Results:</i></b> DTI data were obtained from SVD patients who manifested symptoms of depression (SVD + D) and from control SVD patients (SVD − D). In comparison with SVD − D patients, SVD + D cases demonstrated a diminished coefficient of clustering along with lower global efficiencies and longer path length characteristics. Rich-club analysis showed SVD + D patients had decreased feeder connectivity and local connectivity strengths compared to SVD − D patients. Our data also showed that the feeder connections in the brain correlated significantly with the severity of depression in SVD + D patients. <b><i>Conclusions:</i></b> Our study revealed that SVD patients with depressive symptoms have disrupted white matter networks that characteristically have reduced network efficiency compared to the networks in other SVD patients. Disrupted information interactions among the regions of nonrich-club and rich-club in SVD cases are related to the severity of depression. Our data suggest that DTI may be utilized as an appropriate biomarker for the diagnosis of depression in comorbid SVD patients.

Author(s):  
Salvatore Rudilosso ◽  
Luis Mena ◽  
Diana Esteller ◽  
Marta Olivera ◽  
Juan José Mengual ◽  
...  

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 994
Author(s):  
Natasha Ting Lee ◽  
Lin Kooi Ong ◽  
Prajwal Gyawali ◽  
Che Mohd Nasril Che Mohd Nassir ◽  
Muzaimi Mustapha ◽  
...  

The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood–brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain.


2018 ◽  
Author(s):  
Ayan Dey ◽  
Vessela Stamenova ◽  
Agnes Bacopulos ◽  
Nivethika Jeyakumar ◽  
Gary R. Turner ◽  
...  

Some degree of ischemic injury to white matter tracts occurs naturally with age and is visible on magnetic resonance imaging as focal or confluent white matter hyperintensities (WMHs). Its relationship to cognition, however, remains unclear. To explore this, community-dwelling adults between the ages 55-80 years old completed structural imaging, neuropsychological testing, and questionnaires to provide objective measures and subjective experience of executive functioning. Volumetric lesion burden derived from structural MRI identified those with significant WMH burden (~10 cubic cm). Half of those recruited met this criterion and were designated as the cerebral small vessel disease (CSVD) group. Subjective complaints but not objective test scores differentiated adults with and without CSVD. Hierarchical clustering revealed two CSVD subgroups that differentiated those with impaired versus preserved executive function relative to controls. Overall these results provide some explanation for behavioural heterogeneity often observed in studies of age-related white matter changes. They also support the use of questionnaires to assess subjective complaints that may be able to detect subtle effects of pathology not evident on standardized cognitive scores.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Kayla Navarro ◽  
Ka-ho Wong ◽  
Majd M Ibrahim ◽  
Adam H De Havenon ◽  
Eric Goldstein

Introduction: White matter hyperintensities (WMH) are a radiographic marker for cerebral small vessel disease (CSVD). Conditions altering cerebral venous outflow such as elevated central venous pressure and right atrial pressure in individuals with cardiac valvular disease have been implicated in the development of WMH. Hypothesis: We hypothesize that increased right-heart chamber size in individuals without significant cardiac valvular disease is associated with worse WMH. Methods: A retrospective chart review of adults with a brain MRI and a 2-dimensional transthoracic echocardiogram (TTE) was performed. Worst burden of WMH by way of Fazekas score, either periventricular or deep white matter, served as the primary outcome. Statistical analysis was performed using a multivariate ordinal logistic regression model. Results: A total of 132 individuals were included. Right atrial area (OR 0.93, 95% CI 0.87 to 1.00, p = 0.0041), right ventricular internal diameter (OR 0.48, 95%CI 0.27 to 0.83, p = 0.008) and left atrial area (OR 0.93, 95%CI 0.88 to 0.98, p = 0.007) was identified as being significant. Cardiac functional markers were not significant, including tricuspid annular plane systolic excursion (OR 0.99, 95%CI 0.93 to 1.05, p = 0.670), right ventricular ejection fraction (OR 0.99, 95%CI 0.96 to 1.02, p = 0.670) and left ventricular ejection fraction (OR 0.99, 95%CI 0.96 to 1.02, p = 0.567). Analysis of isolated DWM or PVWM Fazekas scores did not find significant predictors in relation to cardiac structure or function. Conclusions: Through non-invasive cardiac imaging, we identified that cardiac structural abnormalities as opposed to functional abnormalities were associated with worse WMH. Mechanistically this may result from altered intracerebral arteriovenous coupling or a shared pathophysiologic pathway between WMH and coronary microvascular disease.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Susanna Melkas ◽  
Sami Curtze ◽  
Gerli Sibolt ◽  
Niku K Oksala ◽  
Jukka Putaala ◽  
...  

Background: Association between high homocysteine level and cerebral small-vessel disease has been implicated in cross-sectional studies, but results from longitudinal studies have been less clear. The aim of this study was to investigate whether homocysteine level at 3-months poststroke relates to the occurrence of white matter changes (WMC), the surrogate of cerebral small-vessel disease. We also investigated whether it relates to the prognosis after ischemic stroke regarding the risk of dementia at 3-months and mortality in long-term follow-up. Methods: A total of 321 consecutive acute ischemic stroke patients aged 55 to 85 were included in the study and followed up to 12 years. Plasma homocysteine level and occurrence of WMC in MRI were measured 3 months poststroke and dementia according to DSM-III was evaluated at the same time. Findings: The median homocysteine level was 13.50 μmol/l (interquartile range [IQR] 10.60-18.50 μmol/l). Total of 81 patients (25.2%) had homocysteine level above 18.50 μmol/l. In logistic regression analysis, homocysteine level above 18.50 μmol/l was not associated with severe WMC nor with dementia at 3 months poststroke. In Kaplan-Meier analysis, homocysteine level above 18.50 μmol/l was not associated with survival in 12-year follow-up. For further analysis, the group was divided in quartiles according to homocysteine level. The quartiles did not differ in occurrence of severe WMC at baseline, in the risk of dementia at 3 months, nor in the risk of mortality in 12-year follow-up. Interpretation: In our poststroke cohort homocysteine level is not associated with WMC. Further, it does not relate to impaired prognosis manifested as dementia at 3 months or mortality in 12-year follow-up.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1545
Author(s):  
Narek Manukjan ◽  
Zubair Ahmed ◽  
Daniel Fulton ◽  
W. Matthijs Blankesteijn ◽  
Sébastien Foulquier

Key pathological features of cerebral small vessel disease (cSVD) include impairment of the blood brain barrier (BBB) and the progression of white matter lesions (WMLs) amongst other structural lesions, leading to the clinical manifestations of cSVD. The function of endothelial cells (ECs) is of major importance to maintain a proper BBB. ECs interact with several cell types to provide structural and functional support to the brain. Oligodendrocytes (OLs) myelinate axons in the central nervous system and are crucial in sustaining the integrity of white matter. The interplay between ECs and OLs and their precursor cells (OPCs) has received limited attention yet seems of relevance for the study of BBB dysfunction and white matter injury in cSVD. Emerging evidence shows a crosstalk between ECs and OPCs/OLs, mediated by signaling through the Wingless and Int-1 (WNT)/β-catenin pathway. As the latter is involved in EC function (e.g., angiogenesis) and oligodendrogenesis, we reviewed the role of WNT/β-catenin signaling for both cell types and performed a systematic search to identify studies describing a WNT-mediated interplay between ECs and OPCs/OLs. Dysregulation of this interaction may limit remyelination of WMLs and render the BBB leaky, thereby initiating a vicious neuroinflammatory cycle. A better understanding of the role of this signaling pathway in EC–OL crosstalk is essential in understanding cSVD development.


2018 ◽  
Vol 10 (448) ◽  
pp. eaam9507 ◽  
Author(s):  
Rikesh M. Rajani ◽  
Sophie Quick ◽  
Silvie R. Ruigrok ◽  
Delyth Graham ◽  
Sarah E. Harris ◽  
...  

Brain ◽  
2010 ◽  
Vol 134 (1) ◽  
pp. 73-83 ◽  
Author(s):  
K. F. de Laat ◽  
A. M. Tuladhar ◽  
A. G. W. van Norden ◽  
D. G. Norris ◽  
M. P. Zwiers ◽  
...  

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.


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