scholarly journals Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Arunima Kapoor ◽  
Aimée Gaubert ◽  
Anisa Marshall ◽  
Irene B. Meier ◽  
Belinda Yew ◽  
...  
Keyword(s):  
Older Adults ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Signaling Proteins ◽  
Angiogenic Growth Factors ◽  
Vessel Disease ◽  
Increased Risk ◽  
Age And Sex

Background: Cerebral small vessel disease (SVD) is associated with increased risk of stroke and dementia. Progressive damage to the cerebral microvasculature may also trigger angiogenic processes to promote vessel repair. Elevated levels of circulating endothelial progenitor cells (EPCs) and pro-angiogenic signaling proteins are observed in response to vascular injury. We aimed to examine circulating levels of EPCs and proangiogenic proteins in older adults with evidence of SVD.Methods: Older adults (ages 55–90) free of dementia or stroke underwent venipuncture and brain magnetic resonance imaging (MRI). Flow cytometry quantified circulating EPCs as the number of cells in the lymphocyte gate positively expressing EPC surface markers (CD34+CD133+CD309+). Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, and Flt-1). Total SVD burden score was determined based on MRI markers, including white matter hyperintensities, cerebral microbleeds and lacunes.Results: Sixty-four older adults were included. Linear regression revealed that older adults with higher circulating EPC levels exhibited greater total SVD burden [β = 1.0 × 105, 95% CI (0.2, 1.9), p = 0.019], after accounting for age and sex. Similarly, a positive relationship between circulating VEGF-D and total SVD score was observed, controlling for age and sex [β = 0.001, 95% CI (0.000, 0.001), p = 0.048].Conclusion: These findings suggest that elevated levels of circulating EPCs and VEGF-D correspond with greater cerebral SVD burden in older adults. Additional studies are warranted to determine whether activation of systemic angiogenic growth factors and EPCs represents an early attempt to rescue the vascular endothelium and repair damage in SVD.

Total Cerebral Small Vessel Disease Score and Anthropometric Indices: A Population-Based Study in Older Adults of Amerindian Ancestry

2021 ◽  
pp. 1-4
Author(s):  
Oscar H. Del Brutto ◽  
Robertino M. Mera
Keyword(s):  
Older Adults ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
Population Based ◽  
Cerebral Small Vessel Disease ◽  
The Body ◽  
Small Vessel ◽  
Population Based Study ◽  
Vessel Disease ◽  
Ordinal Logistic Regression Model

A total of 590 older adults of Amerindian ancestry living in rural Ecuador received anthropometric measurements and a brain magnetic resonance imaging to estimate the total cerebral small vessel disease (cSVD) score. A fully adjusted ordinal logistic regression model, with categories of the total cSVD score as the dependent variable, disclosed significant associations between the waist circumference, the waist-to-hip, and the waist-to-height ratios – but not the body mass index (BMI) – and the cSVD burden. Indices of abdominal obesity may better correlate with severity of cSVD than the BMI in Amerindians. Phenotypic characteristics of this population may account for these results.

scholarly journals Cerebral small vessel disease or intracranial large vessel atherosclerosis may carry different risk for future strokes

2020 ◽  
Vol 5 (2) ◽  
pp. 128-137
Author(s):  
Huimin Chen ◽  
Yuesong Pan ◽  
Lixia Zong ◽  
Jing Jing ◽  
Xia Meng ◽  
...  
Keyword(s):  
Regression Models ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Arterial Stenosis ◽  
Small Vessel ◽  
Minor Stroke ◽  
Bleeding Events ◽  
Stroke Outcomes ◽  
Vessel Disease ◽  
Increased Risk

BackgroundThe effect of cerebral small vessel disease (CSVD) and intracranial arterial stenosis (ICAS) on stroke outcomes remains unclear.MethodsData of 1045 patients with minor stroke or transient ischaemic attack (TIA) were obtained from 45 sites of the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. We assessed the associations of burdens of CSVD and ICAS with new strokes and bleeding events using multivariate Cox regression models and those with modified Rankin Scale (mRS) scores using ordinal logistic regression models.ResultsAmong the 1045 patients, CSVD was present in 830 cases (79.4%) and ICAS in 460 (44.0%). Patients with >1 ICAS segment showed the highest risk of new strokes (HR 2.03, 95% CI 1.15 to 3.56, p=0.01). No association between CSVD and the occurrence of new strokes was found. The presence of severe CSVD (common OR (cOR) 2.01, 95% CI 1.40 to 2.89, p<0.001) and >1 ICAS segment (cOR 2.15, 95% CI 1.57 to 2.93, p<0.001) was associated with higher mRS scores. Severe CSVD (HR 10.70, 95% CI 1.16 to 99.04, p=0.04), but not ICAS, was associated with a higher risk of bleeding events. Six-point modified CSVD score improved the predictive power for bleeding events and disability.InterpretationCSVD is associated with more disability and bleeding events, and ICAS is associated with an increased risk of stroke and disability in patients with minor stroke and TIA at 3 months. CSVD and ICAS may represent different vascular pathologies and play distinct roles in stroke outcomes.Trial registration numberNCT00979589

scholarly journals Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

2015 ◽  
Vol 36 (1) ◽  
pp. 72-94 ◽  
Author(s):  
Anna Poggesi ◽  
Marco Pasi ◽  
Francesca Pescini ◽  
Leonardo Pantoni ◽  
Domenico Inzitari
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Brain Changes

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.

Abstract WMP59: White Matter Hyperintensities Play a Pivotal Role in Progression of Cerebral Small Vessel Disease: A 7-Year Chinese Urban Community Study

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yiwei Xia ◽  
Yi Shen ◽  
Yi Wang ◽  
Lumeng Yang ◽  
Yiqing Wang ◽  
...  
Keyword(s):  
Executive Function ◽  
Small Vessel Disease ◽  
Urban Community ◽  
Cerebral Small Vessel Disease ◽  
Pivotal Role ◽  
Small Vessel ◽  
Community Study ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Increased Risk

Objective: To explore the role of WMH in progression of CSVD in an urban community in China over a period of 7 years, and to investigate associations between WMH volume (baseline & progression) and cognitive impairment. Methods: CSVD markers and neuropsychological tests at baseline and follow-up of 191 participants of the Shanghai Aging Study (SAS) were assessed. WMH volume were assessed by automatic segmentation based on U-net model. Lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (ePVS) were rated manually. SVD score was rated as the total burden of CSVD markers. We performed multivariate linear regression and binominal logistic regression. We plotted progression of markers by baseline WMH volume in tertile. Results: Participants with higher baseline WMH volume developed more progression of WMH volume, increased risk of incident lacunes, incident CMBs, and ePVS progression. Mean change of WMH volume over 7 years was 4.27mL (0.62mL/y) for all participants, 3.21mL for participants with 1st tertile WMH volume at baseline, 4.19mL for those with 2nd tertile WMH, and 5.43mL for those with 3rd tertile WMH. Incident lacunes and incident CMBs were predominantly seen in participants with 2nd and 3rd tertile WMH. WMH (baseline & progression) were associated with decline of executive function. Conclusions: WMH play a pivotal role in progression of cerebral small vessel disease and are associated with decline of executive function in a Chinese urban community study over a period of 7 years.

scholarly journals Validation of external and internal exposome of the findings associated to cerebral small vessel disease: A Mendelian randomization study

2022 ◽  
pp. 0271678X2210742
Author(s):  
Xue-Qing Zhang ◽  
Yu-Xiang Yang ◽  
Can Zhang ◽  
Xin-Yi Leng ◽  
Shi-Dong Chen ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Fat Free Mass ◽  
Small Vessel ◽  
Sensitivity Analyses ◽  
Vessel Disease ◽  
Increased Risk ◽  
Lobar Hemorrhage ◽  
Health Rating

The exposome characterizes all environmental exposures and their impact on a disease. To determine the causally-associated components of the exposome for cerebral small vessel disease (CSVD), we performed mendelian randomization analysis of 5365 exposures on six clinical and subclinical CSVD measures. We found statistically significant evidence (FDR-corrected P < 0.05) that hypertension, high cholesterol, longer television-watching time, lower educational qualifications, younger age of first sexual intercourse, smoking, reduced pulmonary function, higher subjective overall health rating, and frequent tiredness were associated with increased risk of intracerebral hemorrhage or small vessel stroke. Adiposity, diabetes, frequent alcoholic drinks, higher white blood cell count and neutrophil count were significantly associated with higher risk of non-lobar hemorrhage or small vessel stroke, but not lobar hemorrhage. Hypertension, higher arm or leg fat-free mass and higher sitting height were significantly associated with higher white matter hyperintensities. The results were robust to sensitivity analyses and showed no evidence of horizontal pleiotropy. We also identified 41 exposures suggestively associated (uncorrected P < 0.05) with multiple CSVD measures as the “the CSVD exposome”. This exposome-wide association study provides insight into CSVD development and prevention.

scholarly journals Disrupted Rest-Activity Rhythms and Cerebral Small Vessel Disease Pathology in Older Adults

Stroke ◽  
2021 ◽  
Author(s):  
Rosa Sommer ◽  
Lei Yu ◽  
Julie A. Schneider ◽  
David A. Bennett ◽  
Aron S. Buchman ◽  
...  
Keyword(s):  
Older Adults ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Activity Rhythms ◽  
Logistic Regression Models ◽  
Vessel Disease ◽  
Lower Amplitude ◽  
Rest Activity

Background and Purpose: The pathogenesis of cerebral small vessel disease remains incompletely understood. The relationship between circadian rhythm disturbances and histopathologic measures of cerebral small vessel disease has not been studied. We hypothesized that disrupted circadian rest-activity rhythms would be associated with a higher burden of cerebral small vessel disease pathology. Methods: We studied 561 community-dwelling older adults (mean age at death, 91.2, 27.4% male) from the Rush Memory and Aging Project. We used actigraphy to quantify several measures of 24-hour rest-activity rhythmicity, including interdaily stability, intradaily variability, and amplitude, and used ordinal logistic regression models to relate these measures to the severity of cerebral arteriolosclerosis, atherosclerosis, macroinfarcts, and microinfarcts, assessed at autopsy. Results: Lower interdaily stability was associated with a higher burden of arteriolosclerosis, higher intradaily variability was associated with a higher burden of atherosclerosis and subcortical infarcts, and lower amplitude was associated with a higher burden of arteriosclerosis, atherosclerosis and subcortical macroinfarcts. Moreover, the associations between interdaily stability and arteriolosclerosis and intradaily variability and subcortical infarcts were independent of cardiovascular risk factors, sleep fragmentation, and medical comorbidities. Conclusions: Disrupted rest-activity rhythms are associated with a greater burden of cerebral small vessel disease in older adults.

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