scholarly journals Plasma lipidomic analysis of sphingolipids in patients with large artery atherosclerosis cerebrovascular disease and cerebral small vessel disease

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Qian You ◽  
Qing Peng ◽  
Zemou Yu ◽  
Haiqiang Jin ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrovascular Disease ◽  
Fabry Disease ◽  
High Performance ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Large Artery ◽  
Vessel Disease ◽  
Age Related

Abstract Background: Sphingolipids mainly consist of ceramides (Cer), sphingomyelins (SM) and glycosphingolipids. Sphingolipids are related with coronary heart disease and metabolic disease, but there’re few studies about cerebrovascular disease. The purpose was to detect sphingolipids in plasma of patients with large artery atherosclerosis (LAA) cerebrovascular disease and cerebral small vessel disease (CSVD) to explore the similarities and differences of pathogenesis of the two subtypes. Methods: 20 patients with LAA cerebrovascular disease, 20 patients with age-related CSVD, 10 patients with Fabry disease and 14 controls were enrolled from October 2017 to January 2019. Ultra-high performance liquid chromatography-quadruple-time-of-flight mass spectrometry/mass spectrometry was used to determine sphingolipids. Univariate combined with multivariate analysis was used for comparison. Receiver operating characteristic curves were used to determine sensitivities and specificities. Results: 276 sphingolipids were detected, including 39 Cer, 3 ceramide phosphates, 72 glycosphingolipids and 162 SM. (1) Cer (d36:3), Cer (d34:2), Cer (d38:6), Cer (d36:4) and Cer (d16:0/18:1) were increased in LAA; SM (d34:1), Cer (d34:2), Cer (d36:4), Cer (d16:0/18:1), Cer (d38:6), Cer (d36:3) and Cer (d32:0) were increased in age-related CSVD. (2) Cer (d36:4) and SM (d34:1) were increased in age-related CSVD compared with LAA. (3) Total trihexosyl ceramides were increased in Fabry group compared with control (P<0.05); SM (d34:1) was increased in Fabry group. Conclusions: Ceramides are increased in both LAA and age-related CSVD, which may be related to similar risk factors and pathophysiological process of arteriosclerosis; SM is increased in both age-related CSVD and Fabry disease, suggesting that increased SM may be associated with CSVD. Glycosphingolipids, trihexosylceramides in particular, are increased in Fabry disease.

scholarly journals Cognitive heterogeneity among community-dwelling older adults with Cerebral Small Vessel Disease

2018 ◽  
Author(s):  
Ayan Dey ◽  
Vessela Stamenova ◽  
Agnes Bacopulos ◽  
Nivethika Jeyakumar ◽  
Gary R. Turner ◽  
...  
Keyword(s):  
White Matter ◽  
Subjective Experience ◽  
Small Vessel Disease ◽  
Neuropsychological Testing ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Vessel Disease ◽  
Age Related ◽  
Subjective Complaints

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.

scholarly journals Associations between blood and cerebrospinal fluid flow impairments assessed with phase-contrast MRI and brain damage in patients with age-related cerebral small vessel disease

2019 ◽  
pp. 16-23
Author(s):  
E.I. Kremneva ◽  
B.M. Akhmetzyanov ◽  
L.A. Dobrynina ◽  
M.V. Krotenkova
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Damage ◽  
Phase Contrast ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Csf Flow ◽  
Phase Contrast Mri ◽  
Vessel Disease ◽  
Age Related

Hemodynamic parameters of blood and cerebrospinal fluid (CSF) flow can be measured in vivo using phase-contrast MRI (PC-MRI). This opens new horizons for studying the mechanisms implicated in the development and progression of age-related cerebral small vessel disease (SVD). In this paper, we analyze associations between cerebral arterial, venous and CSF flow impairments and SVD features visible on MRI. The study was carried out in 96 patients with SVD (aged 60.91 ± 6.57 years) and 23 healthy volunteers (59.13 ± 6.56 years). The protocol of the MRI examination included routine MRI sequences (T2, FLAIR, T1, SWI, and DWI) applied to assess the severity of brain damage according to STRIVE advisory standards and PC-MRI used to quantify blood flow in the major arteries and veins of the neck, the straight and upper sagittal sinuses, and CSF flow at the aqueduct level. We analyzed the associations between linear and volumetric parameters of blood/CSF flow and the degree of brain matter damage using the Fazekas scale. We observed a reduction in tABF, stVBF, sssVBF, aqLF, Saq, and ICC values and a rise in Pi associated with WMH progression, as well as a gradual decline in tABF and an increase in Pi, Saq and ICC associated with a growing number of lacunes (р < 0.05). Patients with early (< 5) MB had lower sssVBF and stVBF rates in comparison with patients without MB; aqLF, Saq, and ICC values were elevated in patients with 5 to 10 MB, as compared to patients without MB or early (< 5) MB. The established associations between MRI findings in patients with SVD and blood/CSF flow impairments suggest the important role of mechanisms implicated in the disruption of Monro–Kellie intracranial homeostasis in promoting SVD.

Abstract T MP57: Coexisting Cerebrovascular Disease and Risk of Occult Atrial Fibrillation in Patients With Embolic Stroke of Undetermined Source

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Esther Rojo ◽  
María Sandín-Fuentes ◽  
Ana I Calleja ◽  
Gabriel Largaespada ◽  
Elisa Cortijo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Secondary Prevention ◽  
Cerebrovascular Disease ◽  
Cox Regression ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
Embolic Stroke ◽  
Small Vessel ◽  
Large Artery ◽  
Vessel Disease

Background and objective: Secondary prevention after embolic stroke of undetermined source (ESUS) remains a clinical problem. Presence of asymptomatic cerebral large-artery atherosclerosis or small vessel disease could be aprioristically taken as an indicator of a lower risk for an occult cardiac source of emboli, thus influencing our secondary prevention strategy. We aimed to study the relationship between presence and degree of coexisting cerebrovascular disease and the risk of occult paroxysmal atrial fibrillation (OPAF) in ESUS patients. Methods: Longitudinal prospective study in patients fulfilling ESUS criteria after complete neurovascular and cardiac diagnostic workup, who were implanted with a subcutaneous REVEAL-XT loop-recorder to detect OPAF and followed-up for≥ 6 months. At baseline, cerebral large-artery atherosclerosis was assessed with cervical and transcranial ultrasound. Brain magnetic resonance imaging was used to evaluate small vessel disease. Periventricular (PV) and subcortical (SC) white matter hiperintensities (WMH) were categorized using the Fazekas score. Results: We studied 136 ESUS patients from October 2010 to December 2013 (71 men, mean age 67), who were followed-up for a mean time of 594 days. OPAF was detected in 56 (41%) of them. No relationship was found between extracranial or intracranial atherosclerosis and OPAF. Kaplan-Meier curves and crude Cox-regression analyses found associations between OPAF risk and age, smoking, CHA2DS2VASC score, presence of lacunar infarctions, and presence and degree of PVWMH & SCWMH. A multivariable-adjusted Cox regression model identified grade 2-3 PVWMH (HR 3.6, [2.0-6.5], p<0.001) and age as independent predictors of OPAF. Conclusion: Coexisting small vessel disease, specifically in the form of periventricular WMH, is a predictor of OPAF in ESUS patients. Presence of large-artery atherosclerosis does not lower the risk for OPAF. Therefore, OPAF should be actively pursued in ESUS patients regardless the coexistence of asymptomatic cerebrovascular disease.

scholarly journals Contributions of Aging to Cerebral Small Vessel Disease

2020 ◽  
Vol 82 (1) ◽  
pp. 275-295 ◽  
Author(s):  
T. Michael De Silva ◽  
Frank M. Faraci
Keyword(s):  
Recent Progress ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Brain Health ◽  
Vessel Disease ◽  
Age Related ◽  
The Face ◽  
Basic Biology ◽  
The Impact

Cerebral small vessel disease (SVD) is characterized by changes in the pial and parenchymal microcirculations. SVD produces reductions in cerebral blood flow and impaired blood-brain barrier function, which are leading contributors to age-related reductions in brain health. End-organ effects are diverse, resulting in both cognitive and noncognitive deficits. Underlying phenotypes and mechanisms are multifactorial, with no specific treatments at this time. Despite consequences that are already considerable, the impact of SVD is predicted to increase substantially with the growing aging population. In the face of this health challenge, the basic biology, pathogenesis, and determinants of SVD are poorly defined. This review summarizes recent progress and concepts in this area, highlighting key findings and some major unanswered questions. We focus on phenotypes and mechanisms that underlie microvascular aging, the greatest risk factor for cerebrovascular disease and its subsequent effects.

scholarly journals A population neuroscience approach to the study of cerebral small vessel disease in midlife and late life: an invited review

2018 ◽  
Vol 314 (6) ◽  
pp. H1117-H1136 ◽  
Author(s):  
Dana R. Jorgensen ◽  
C. Elizabeth Shaaban ◽  
Clayton A. Wiley ◽  
Peter J. Gianaros ◽  
Joseph Mettenburg ◽  
...  
Keyword(s):  
Risk Factors ◽  
Small Vessel Disease ◽  
Later Life ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cross Sectional ◽  
Vessel Disease ◽  
Age Related ◽  
Cerebral Microvasculature ◽  
Study Designs

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.

scholarly journals Cell Senescence and Cerebral Small Vessel Disease in the Brains of People Aged 80 Years and Older

2019 ◽  
Vol 78 (11) ◽  
pp. 1066-1072 ◽  
Author(s):  
Emma J Norton ◽  
Leslie R Bridges ◽  
Lawrence C Kenyon ◽  
Margaret M Esiri ◽  
Dorothy C Bennett ◽  
...  
Keyword(s):  
Cell Density ◽  
Older Persons ◽  
Small Vessel Disease ◽  
Subcortical White Matter ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Mural Cell ◽  
Mural Cells ◽  
Vessel Disease ◽  
Age Related

Abstract Cerebral small vessel disease (cSVD) in penetrating arteries is a major cause of age-related morbidity. Cellular senescence is a molecular process targeted by novel senolytic drugs. We quantified senescence in penetrating arteries and tested whether myocyte senescence was associated with cSVD. We immunolabeled subcortical white matter of older persons (age 80–96 years, n = 60) with minimal AD, using antibodies to 2 established senescence markers (H3K9me3, γH2AX) and a myocyte marker (hSMM). Within the walls of penetrating arteries (20–300 µm), we quantified senescence-associated heterochromatic foci (SAHF)-positive nuclei, cell density (nuclei/µm2), and sclerotic index (SI). Senescent-appearing mural cells were present in small arteries of all cases. cSVD cases exhibited a lower proportion of senescent-appearing cells and lower area fraction (AF%) of SAHF-positive nuclei compared to controls (p = 0.014, 0.016, respectively). cSVD severity and SI both correlated negatively with AF% (p = 0.013, 0.002, respectively). Mural cell density was lower (p < 0.001) and SI higher (p < 0.001) in cSVD, relative to controls. In conclusion, senescent myocyte-like cells were universal in penetrating arteries of an AD-free cohort aged 80 years and older. Senescent-appearing nuclei were more common in persons aged 80 years and older without cSVD compared to cSVD cases, indicating caution in senolytic drug prescribing. Myocyte senescence and cSVD may represent alternative vessel fates in the aging human brain.

scholarly journals Genetic overlap and causal inferences between kidney function and cerebrovascular disease

Neurology ◽  
2020 ◽  
Vol 94 (24) ◽  
pp. e2581-e2591 ◽  
Author(s):  
Sandro Marini ◽  
Marios K. Georgakis ◽  
Jaeyoon Chung ◽  
Jonathan Q.A. Henry ◽  
Martin Dichgans ◽  
...  
Keyword(s):  
Cerebrovascular Disease ◽  
Kidney Function ◽  
Mendelian Randomization ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Large Artery ◽  
Disease Phenotypes ◽  
Vessel Disease ◽  
Genetic Overlap ◽  
Lower Egfr

ObjectiveLeveraging large-scale genetic data, we aimed to identify shared pathogenic mechanisms and causal relationships between impaired kidney function and cerebrovascular disease phenotypes.MethodsWe used summary statistics from genome-wide association studies (GWAS) of kidney function traits (chronic kidney disease diagnosis, estimated glomerular filtration rate [eGFR], and urinary albumin-to-creatinine ratio [UACR]) and cerebrovascular disease phenotypes (ischemic stroke and its subtypes, intracerebral hemorrhage [ICH], and white matter hyperintensities [WMH] on brain MRI). We (1) tested the genetic overlap between them with polygenic risk scores (PRS), (2) searched for common pleiotropic loci with pairwise GWAS analyses, and (3) explored causal associations by employing 2-sample Mendelian randomization.ResultsA PRS for lower eGFR was associated with higher large artery stroke (LAS) risk (p = 1 × 10−4). Multiple pleiotropic loci were identified between kidney function traits and cerebrovascular disease phenotypes, with 12q24 associated with eGFR and both LAS and small vessel stroke (SVS), and 2q33 associated with UACR and both SVS and WMH. Mendelian randomization revealed associations of both lower eGFR (odds ratio [OR] per 1-log decrement, 2.10; 95% confidence interval [CI], 1.38–3.21) and higher UACR (OR per 1-log increment, 2.35; 95% CI, 1.12–4.94) with a higher risk of LAS, as well as between higher UACR and higher risk of ICH.ConclusionsImpaired kidney function, as assessed by decreased eGFR and increased UACR, may be causally involved in the pathogenesis of LAS. Increased UACR, previously proposed as a marker of systemic small vessel disease, is involved in ICH risk and shares a genetic risk factor at 2q33 with manifestations of cerebral small vessel disease.

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