scholarly journals Extracerebral microvascular dysfunction is related to brain MRI markers of cerebral small vessel disease: The Maastricht Study

GeroScience ◽  
2021 ◽  
Author(s):  
Maud van Dinther ◽  
Miranda T. Schram ◽  
Jacobus F. A. Jansen ◽  
Walter H. Backes ◽  
Alfons J. H. M. Houben ◽  
...  

Abstract Background Cerebral small vessel disease (cSVD) is a late consequence of cerebral microvascular dysfunction (MVD). MVD is hard to measure in the brain due to its limited accessibility. Extracerebral MVD (eMVD) measures can give insights in the etiology of cerebral MVD, as MVD may be a systemic process. We aim to investigate whether a compound score consisting of several eMVD measures is associated with structural cSVD MRI markers. Methods Cross-sectional data of the population-based Maastricht Study was used (n = 1872, mean age 59 ± 8 years, 49% women). Measures of eMVD included flicker light-induced retinal arteriolar and venular dilation response (retina), albuminuria and glomerular filtration rate (kidney), heat-induced skin hyperemia (skin), and plasma biomarkers of endothelial dysfunction (sICAM-1, sVCAM-1, sE-selectin, and von Willebrand factor). These measures were standardized into z scores and summarized into a compound score. Linear and logistic regression analyses were used to investigate the associations between the compound score and white matter hyperintensity (WMH) volume, and the presence of lacunes and microbleeds, as measured by brain MRI. Results The eMVD compound score was associated with WMH volume independent of age, sex, and cardiovascular risk factors (St β 0.057 [95% CI 0.010–0.081], p value 0.01), but not with the presence of lacunes (OR 1.011 [95% CI 0.803–1.273], p value 0.92) or microbleeds (OR 1.055 [95% CI 0.896–1.242], p value 0.52). Conclusion A compound score of eMVD is associated with WMH volume. Further research is needed to expand the knowledge about the role of systemic MVD in the pathophysiology of cSVD.

2021 ◽  
pp. 1-4
Author(s):  
Oscar H. Del Brutto ◽  
Robertino M. Mera

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.


2015 ◽  
Vol 22 (11) ◽  
pp. 1482-1487 ◽  
Author(s):  
L. A. Zuurbier ◽  
M. A. Ikram ◽  
A. I. Luik ◽  
A. Hofman ◽  
E. J. W. Van Someren ◽  
...  

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Forrest Lowe ◽  
Souvik Sen ◽  
Hamdi S Adam ◽  
Ryan Demmer ◽  
Bruce A Wasserman ◽  
...  

Background: Prior studies have shown the association between periodontal disease, lacunar strokes and cognitive impairment. Using the Atherosclerosis Risk in Communities (ARIC) cohort study we investigated the relationship between periodontal disease (PD) and the development of MRI verified small vessel disease. Methods: Using the ARIC database data we extracted data for 1143 (mean age 77 years, 76% white, 24% African-American and 45% male) participants assessed for PD (N=800) versus periodontal health (N=343). These participants were assessed for small vessel disease on 3T MRI as measured by the log of white matter hyperintensity volume (WMHV). WMHV were derived from a semiautomated segmentation of FLAIR images. Student t-test was then used to evaluate the relationship between small vessel disease as the log of WMHV in subjects with PD or periodontal health. Based on WMHV the patients were grouped into quartiles and the association of PD with WMHV were tested using the group in periodontal health and lowest quartile of WMHV as the reference groups. Multinomial logistic regression was used to compute crude and adjusted odds ratio (OR) for the higher quartiles of WMHV compared to the reference quartile. Results: There was a significant increase in the presence of small vessel disease measured as log WMHV in the PD cohort as compared to periodontal health cohort with p= 0.023 on Independent Sample t-est. Based on WMHV the subjects were grouped into quartiles 0-6.41, >6.41-11.56, >11.56-21.36 and >21.36 cu mm3). PD was associated with only the highest quartile of WMHV on univariate (crude OR 1.77, 95% CI 1.23-2.56) and multivariable (adjusted OR 1.61, 95% CI 1.06-2.44) analyses. The later was adjusted for age, race, gender, hypertension, diabetes and smoking. Conclusion: Based on this prospective cohort there is data to suggest that PD may be associated with cerebral small vessel disease. Maintaining proper dental health may decrease future risk for the associated lacunar strokes and vascular cognitive impairment.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Dorothee Schoemaker ◽  
Yesica Zuluaga ◽  
Lina Velilla ◽  
Carolina Ospina ◽  
Francisco Lopera ◽  
...  

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease (cSVD) linked to NOTCH3 mutations and leading to the early onset of stroke and vascular cognitive impairment. Neuroimaging features of CADASIL include extensive white matter hyperintensity, lacunes, cerebral microbleeds and enlarged perivascular spaces. Researchers from the Rotterdam study recently proposed a MRI-based cSVD Score reflecting the overall burden of cerebrovascular injury (Yilmaz et al., 2018). Here, we explored the relevance of this cSVD Score in distinguishing CADASIL subjects from non-carriers and its relationships to cognition. We evaluated 26 NOTCH3 mutation carriers and 25 non-carriers from large Colombian families. Of the CADASIL subjects, 4 had previous strokes (symptomatic) and 22 had no history of strokes (asymptomatic). All subjects underwent a 3T MRI and a neuropsychological evaluation. Structural MRI markers of cSVD, as well as the cSVD Score, were quantified in each subject following established protocols. Demographic, cognitive and neuroimaging features across groups are presented in Table 1. The cSVD Score significantly differed between groups, after adjusting for age (Figure 1-A). In CADASIL subjects, the cSVD Score was negatively related to performance in Memory, Processing Speed, Executive Function, after accounting for age and education (Figure 1-B). These results suggest that the cSVD Score could be a useful marker of disease severity in CADASIL. Longitudinal studies are now needed to determine if this score allows predicting clinical outcomes in CADASIL, such as stroke or dementia.


2021 ◽  
Vol 21 ◽  
Author(s):  
Leonardo Ulivi ◽  
Mirco Cosottini ◽  
Gianmichele Migaleddu ◽  
Giovanni Orlandi ◽  
Nicola Giannini ◽  
...  

: Monogenic cerebral small vessel diseases are a topic of growing interest, as several genes responsible have been recently described and new sequencing techniques such as Next generation sequencing are available. Brain imaging is a key exam in these diseases. First, since it is often the first exam performed, an MRI is key in selecting patients for genetic testing and for interpreting Next generation sequencing reports. In addition, neuroimaging can be helpful in describing the underlying pathological mechanisms involved in cerebral small vessel disease. With this review, we aim to provide Neurologists and Stroke physicians with an up-to date overview of the current neuroimaging knowledge on monogenic small vessel diseases.


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.


2018 ◽  
Vol 314 (6) ◽  
pp. H1117-H1136 ◽  
Author(s):  
Dana R. Jorgensen ◽  
C. Elizabeth Shaaban ◽  
Clayton A. Wiley ◽  
Peter J. Gianaros ◽  
Joseph Mettenburg ◽  
...  

Aging in later life engenders numerous changes to the cerebral microvasculature. Such changes can remain clinically silent but are associated with greater risk for negative health outcomes over time. Knowledge is limited about the pathogenesis, prevention, and treatment of potentially detrimental changes in the cerebral microvasculature that occur with advancing age. In this review, we summarize literature on aging of the cerebral microvasculature, and we propose a conceptual framework to fill existing research gaps and advance future work on this heterogeneous phenomenon. We propose that the major gaps in this area are attributable to an incomplete characterization of cerebrovascular pathology, the populations being studied, and the temporality of exposure to risk factors. Specifically, currently available measures of age-related cerebral microvasculature changes are indirect, primarily related to parenchymal damage rather than direct quantification of small vessel damage, limiting the understanding of cerebral small vessel disease (cSVD) itself. Moreover, studies seldom account for variability in the health-related conditions or interactions with risk factors, which are likely determinants of cSVD pathogenesis. Finally, study designs are predominantly cross-sectional and/or have relied on single time point measures, leaving no clear evidence of time trajectories of risk factors or of change in cerebral microvasculature. We argue that more resources should be invested in 1) developing methodological approaches and basic science models to better understand the pathogenic and etiological nature of age-related brain microvascular diseases and 2) implementing state-of-the-science population study designs that account for the temporal evolution of cerebral microvascular changes in diverse populations across the lifespan.


2019 ◽  
Vol 20 (3) ◽  
pp. 776 ◽  
Author(s):  
Michael Thrippleton ◽  
Gordon Blair ◽  
Maria Valdes-Hernandez ◽  
Andreas Glatz ◽  
Scott Semple ◽  
...  

A protocol for evaluating ultrasmall superparamagnetic particles of iron oxide (USPIO) uptake and elimination in cerebral small vessel disease patients was developed and piloted. B1-insensitive R1 measurement was evaluated in vitro. Twelve participants with history of minor stroke were scanned at 3-T MRI including structural imaging, and R1 and R2* mapping. Participants were scanned (i) before and (ii) after USPIO (ferumoxytol) infusion, and again at (iii) 24–30 h and (iv) one month. Absolute and blood-normalised changes in R1 and R2* were measured in white matter (WM), deep grey matter (GM), white matter hyperintensity (WMH) and stroke lesion regions. R1 measurements were accurate across a wide range of values. R1 (p < 0.05) and R2* (p < 0.01) mapping detected increases in relaxation rate in all tissues immediately post-USPIO and at 24–30 h. R2* returned to baseline at one month. Blood-normalised R1 and R2* changes post-infusion and at 24–30 h were similar, and were greater in GM versus WM (p < 0.001). Narrower distributions were seen with R2* than for R1 mapping. R1 and R2* changes were correlated at 24–30 h (p < 0.01). MRI relaxometry permits quantitative evaluation of USPIO uptake; R2* appears to be more sensitive to USPIO than R1. Our data are explained by intravascular uptake alone, yielding estimates of cerebral blood volume, and did not support parenchymal uptake. Ferumoxytol appears to be eliminated at 1 month. The approach should be valuable in future studies to quantify both blood-pool USPIO and parenchymal uptake associated with inflammatory cells or blood-brain barrier leak.


Neurology ◽  
2020 ◽  
Vol 95 (24) ◽  
pp. e3331-e3343 ◽  
Author(s):  
Maria J. Knol ◽  
Dongwei Lu ◽  
Matthew Traylor ◽  
Hieab H.H. Adams ◽  
José Rafael J. Romero ◽  
...  

ObjectiveTo identify common genetic variants associated with the presence of brain microbleeds (BMBs).MethodsWe performed genome-wide association studies in 11 population-based cohort studies and 3 case–control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel. BMBs were rated on susceptibility-weighted or T2*-weighted gradient echo MRI sequences, and further classified as lobar or mixed (including strictly deep and infratentorial, possibly with lobar BMB). In a subset, we assessed the effects of APOE ε2 and ε4 alleles on BMB counts. We also related previously identified cerebral small vessel disease variants to BMBs.ResultsBMBs were detected in 3,556 of the 25,862 participants, of which 2,179 were strictly lobar and 1,293 mixed. One locus in the APOE region reached genome-wide significance for its association with BMB (lead single nucleotide polymorphism rs769449; odds ratio [OR]any BMB [95% confidence interval (CI)] 1.33 [1.21–1.45]; p = 2.5 × 10−10). APOE ε4 alleles were associated with strictly lobar (OR [95% CI] 1.34 [1.19–1.50]; p = 1.0 × 10−6) but not with mixed BMB counts (OR [95% CI] 1.04 [0.86–1.25]; p = 0.68). APOE ε2 alleles did not show associations with BMB counts. Variants previously related to deep intracerebral hemorrhage and lacunar stroke, and a risk score of cerebral white matter hyperintensity variants, were associated with BMB.ConclusionsGenetic variants in the APOE region are associated with the presence of BMB, most likely due to the APOE ε4 allele count related to a higher number of strictly lobar BMBs. Genetic predisposition to small vessel disease confers risk of BMB, indicating genetic overlap with other cerebral small vessel disease markers.


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