Abstract TP172: Pulmonary Function and White Matter Hyperintensity in Neurologically Healthy Adults

Introduction: Cerebral small vessel disease (SVD) is considered as precursor lesion of many clinical outcomes including stroke and dementia. It is well established that obstructive sleep apnea or chronic obstructive pulmonary disease is an independent risk factor of stroke. However, there are few studies about the association between pulmonary function and the presence of cerebral small vessel disease. Purpose: This study aims to investigate the association between pulmonary function and cerebral SVD in healthy adults. Methods: We conducted a cross-sectional study of 1,528 neurologically healthy people (mean age 56.0±9.0; 847 men), who underwent brain MRI and pulmonary function tests (forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1 )). Risk factors, anthropometric parameters and clinical information were obtained. For evaluating cerebral SVD, the presence of small silent infarction (SSI) and the volume of white matter hyperintensity (WMH) were assessed through axial T2 fluid-attenuated inversion recovery (FLAIR) sequences MRI. Cerebral microbleeds (CMBs) were evaluated through T2-weighted gradient-recalled echo MRI. Results: The prevalence of SSI and CMBs were 9.6% (147 subjects) and 4.1% (63 subjects), respectively. The mean volume of WMH was 2.8±6.2mm 3 . In multiple regression analysis that controlled for age, sex, and smoking status, FVC had a significant negative correlation with WMH volume (R 2 =0.005, β=-0.109, p=0.002), and FEV 1 /FVC ratio had a significant correlation with WMH volume (R 2 =0.006, β=0.083, p=<0.001). In multivariable logistic analysis, after adjusting age, gender, hypertension, and glucose, FVC was negatively associated with the presence of SSI (adjusted OR 0.63, 95% CI 0.44-0.91), and FEV 1 /FVC ratio was positively associated with the presence of SSI (adjusted OR 1.05, 95% CI 1.02-1.08). The presence of CMBs was not associated with any factor of pulmonary function tests. Conclusions: The results from our study suggest that lower pulmonary function, especially FVC, was found to be an independent risk factor of cerebral SVD in neurologically healthy adults.

Download Full-text

Fibrinogen is an Independent Risk Factor for White Matter Hyperintensities in CADASIL but not in Sporadic Cerebral Small Vessel Disease Patients

Aging and Disease ◽

10.14336/ad.2020.1110 ◽

2021 ◽

Vol 12 (3) ◽

pp. 801

Author(s):

Xingfang Guo ◽

Bin Deng ◽

Lizi Zhong ◽

Fen Xie ◽

Qing Qiu ◽

...

Keyword(s):

Risk Factor ◽

White Matter ◽

Independent Risk Factor ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease

Download Full-text

MRI Relaxometry for Quantitative Analysis of USPIO Uptake in Cerebral Small Vessel Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20030776 ◽

2019 ◽

Vol 20 (3) ◽

pp. 776 ◽

Cited By ~ 2

Author(s):

Michael Thrippleton ◽

Gordon Blair ◽

Maria Valdes-Hernandez ◽

Andreas Glatz ◽

Scott Semple ◽

...

Keyword(s):

White Matter ◽

Cerebral Blood Volume ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Minor Stroke ◽

Vessel Disease ◽

Wide Range

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.

Download Full-text

Abstract 49: White Matter Hyperintensity Spatial Pattern Variations reflect distinct Cerebral Small Vessel Disease Pathologies

Stroke ◽

10.1161/str.50.suppl_1.49 ◽

2019 ◽

Vol 50 (Suppl_1) ◽

Author(s):

Chia-Ling Phuah ◽

Yasheng Chen ◽

Ziyang Liu ◽

Nirupama Yechoor ◽

Helen Hwang ◽

...

Keyword(s):

White Matter ◽

Spatial Pattern ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Vessel Disease

Download Full-text

Progression of MRI markers in cerebral small vessel disease: Sample size considerations for clinical trials

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2015.113 ◽

2015 ◽

Vol 36 (1) ◽

pp. 228-240 ◽

Cited By ~ 44

Author(s):

Philip Benjamin ◽

Eva Zeestraten ◽

Christian Lambert ◽

Irina Chis Ster ◽

Owen A Williams ◽

...

Keyword(s):

White Matter ◽

Sample Size ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Cognitive Change ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Vessel Disease ◽

Size Estimates

Detecting treatment efficacy using cognitive change in trials of cerebral small vessel disease (SVD) has been challenging, making the use of surrogate markers such as magnetic resonance imaging (MRI) attractive. We determined the sensitivity of MRI to change in SVD and used this information to calculate sample size estimates for a clinical trial. Data from the prospective SCANS (St George’s Cognition and Neuroimaging in Stroke) study of patients with symptomatic lacunar stroke and confluent leukoaraiosis was used ( n = 121). Ninety-nine subjects returned at one or more time points. Multimodal MRI and neuropsychologic testing was performed annually over 3 years. We evaluated the change in brain volume, T2 white matter hyperintensity (WMH) volume, lacunes, and white matter damage on diffusion tensor imaging (DTI). Over 3 years, change was detectable in all MRI markers but not in cognitive measures. WMH volume and DTI parameters were most sensitive to change and therefore had the smallest sample size estimates. MRI markers, particularly WMH volume and DTI parameters, are more sensitive to SVD progression over short time periods than cognition. These markers could significantly reduce the size of trials to screen treatments for efficacy in SVD, although further validation from longitudinal and intervention studies is required.

Download Full-text

Carotid Atheroinflammation Is Associated With Cerebral Small Vessel Disease Severity

Frontiers in Neurology ◽

10.3389/fneur.2021.690935 ◽

2021 ◽

Vol 12 ◽

Author(s):

Nicholas R. Evans ◽

Jason M. Tarkin ◽

Jessica Walsh ◽

Mohammed M. Chowdhury ◽

Andrew J. Patterson ◽

...

Keyword(s):

White Matter ◽

Carotid Artery ◽

Disease Severity ◽

Small Vessel Disease ◽

Imaging Study ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Vessel Disease ◽

Systemic Inflammatory Disease

Background: Atherosclerosis is a systemic inflammatory disease, with common inflammatory processes implicated in both atheroma vulnerability and blood-brain barrier disruption. This prospective multimodal imaging study aimed to measure directly the association between systemic atheroma inflammation (“atheroinflammation”) and downstream chronic cerebral small vessel disease severity.Methods: Twenty-six individuals with ischemic stroke with ipsilateral carotid artery stenosis of >50% underwent 18fluoride-fluorodeoxyglucose-positron emission tomography within 2 weeks of stroke. Small vessel disease severity and white matter hyperintensity volume were assessed using 3-tesla magnetic resonance imaging also within 2 weeks of stroke.Results: Fluorodeoxyglucose uptake was independently associated with more severe small vessel disease (odds ratio 6.18, 95% confidence interval 2.1–18.2, P < 0.01 for the non-culprit carotid artery) and larger white matter hyperintensity volumes (coefficient = 14.33 mL, P < 0.01 for the non-culprit carotid artery).Conclusion: These proof-of-concept results have important implications for our understanding of the neurovascular interface and potential therapeutic exploitation in the management of systemic atherosclerosis, particularly non-stenotic disease previously considered asymptomatic, in order to reduce the burden of chronic cerebrovascular disease.

Download Full-text

The Relationship Between ADAMTS13 Activity and Overall Cerebral Small Vessel Disease Burden: A Cross-Sectional Study Based on CSVD

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.738359 ◽

2021 ◽

Vol 13 ◽

Author(s):

Wenbo Sun ◽

Yufan Luo ◽

Shufan Zhang ◽

Wenmei Lu ◽

Luqiong Liu ◽

...

Keyword(s):

White Matter ◽

Confidence Interval ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Adamts13 Activity ◽

Vessel Disease ◽

The Mean ◽

Subcortical Infarction

Objectives: This study aimed to investigate the association between plasma von Willebrand factor (VWF) level, ADAMTS13 activity, and neuroimaging features of cerebral small vessel disease (CSVD), including the CSVD neuroimaging markers and the overall CSVD burden.Methods: CSVD patients admitted to our hospital from 2016 to 2020 were recruited. Plasma VWF level and ADAMTS13 activity were measured. The overall effect of CSVD on the brain was described as a validated CSVD score. We evaluated the association between VWF levels, ADAMTS13 activity, and the increasing severity of CSVD score by the logistic regression model.Results: We enrolled 296 patients into this study. The mean age of the sample was 69.0 years (SD 7.0). The mean VWF level was 1.31 IU/mL, and the ADAMTS13 activity was 88.01 (SD 10.57). In multivariate regression analysis, lower ADAMTS13 activity and higher VWF level was related to white matter hyperintensity (WMH) [β = −7.31; 95% confidence interval (CI) (−9.40, −4.93); p<0.01; β = 0.17; 95% confidence interval (0.11, 0.23); p<0.01], subcortical infarction (SI) [(β = −9.22; 95% CI (−11.37, −7.06); p<0.01); β = 0.21; 95% confidence interval (0.15, 0.27); p<0.01] independently, but not cerebral microbleed (CMB) [(β = −2.3; 95% CI (−4.95, 0.05); p = 0.22); β = 0.02; 95% confidence interval (−0.05, 0.08); p = 0.63]. Furthermore, ADAMTS13 activity was independently negatively correlated with the overall CSVD burden (odd ratio = 21.33; 95% CI (17.46, 54.60); p < 0.01) after adjustment for age, history of hypertension, and current smoking.Conclusions: Reducing ADAMTS13 activity change is related to white matter hyperintensity, subcortical infarction, but not with cerebral microhemorrhage. In addition, ADAMTS13 may have played an essential role in the progression of CSVD.

Download Full-text

Serum homocysteine level is related to cerebral small vessel disease in a healthy population

Neurology ◽

10.1212/wnl.0000000000006816 ◽

2019 ◽

Vol 92 (4) ◽

pp. e317-e325 ◽

Cited By ~ 11

Author(s):

Ki-Woong Nam ◽

Hyung-Min Kwon ◽

Han-Yeong Jeong ◽

Jin-Ho Park ◽

Hyuktae Kwon ◽

...

Keyword(s):

White Matter ◽

Odds Ratio ◽

Adjusted Odds Ratio ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

White Matter Hyperintensity ◽

Healthy Population ◽

Dependent Manner ◽

Vessel Disease ◽

Dose Dependent

ObjectiveTo evaluate the relationship between serum total homocysteine (tHcy) levels and cerebral small vessel disease (cSVD) in a healthy population.MethodsWe included consecutive participants who visited our department for health checkups between 2006 and 2013. We rated white matter hyperintensity volumes using both the Fazekas score and semiautomated quantitative methods. We also evaluated lacunes, cerebral microbleeds, and enlarged perivascular spaces (EPVS), which are involved in cSVD. To assess the dose-dependent relationship between tHcy and cSVD parameters, we scored the burdens of each radiologic marker of cSVD.ResultsA total of 1,578 participants were included (age 55 ± 8 years, male sex 57%). In the multivariable analysis, tHcy remained an independent predictor of the white matter hyperintensity volume (B = 0.209; 95% confidence interval [CI] = 0.033–0.385, p = 0.020), presence of cerebral microbleeds (adjusted odds ratio = 2.800; 95% CI = 1.104–7.105, p = 0.030), and moderate to severe EPVS (adjusted odds ratio = 5.906; 95% CI = 3.523–9.901, p < 0.001) after adjusting for confounders. Furthermore, tHcy had positive associations with periventricular Fazekas score (p = 0.001, p for trend <0.001), subcortical Fazekas score (p = 0.003, p for trend = 0.005), and moderate to severe EPVS lesion burden (p < 0.001, p for trend <0.001) in a dose-dependent manner.ConclusionsSerum tHcy level is correlated with cSVD development in a dose-dependent manner. These findings provide us with clues for further studies of the pathophysiology of cSVD.

Download Full-text

Fixel-Based Analysis of White Matter Alterations in Early- Stage Cerebral Small Vessel Disease

10.21203/rs.3.rs-772604/v1 ◽

2021 ◽

Author(s):

Marvin Petersen ◽

Benedikt M. Frey ◽

Carola Mayer ◽

Simone Kühn ◽

Jürgen Gallinat ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Early Stage ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Health Study ◽

Vessel Disease ◽

Early Stages

Abstract Cerebral small vessel disease (CSVD) is a common cause of morbidity and cognitive decline in the elderly population. However, characterizing the disease pathophysiology and its association with potential clinical sequelae in early stages is less well explored. We applied fixel-based analysis (FBA), a novel framework of investigating microstructural white matter integrity by diffusion-weighted imaging, to data of 921 participants of the Hamburg City Health Study, comprising middle-aged individuals with increased cerebrovascular risk in early stages of CSVD. In individuals in the highest quartile of white matter hyperintensity loads (n=232, median age 63 years; IQR 15.3 years), FBA detected significantly reduced axonal density and increased atrophy of transcallosal fiber tracts, the bilateral superior longitudinal fasciculus, and corticospinal tracts compared to participants in the lowest quartile of white matter hyperintensities (n=228, mean age 55 years; IQR 10 years). Analysis of all participants (N=921) demonstrated a significant association between reduced fiber density and worse executive functions operationalized by the Trail Making Test. Findings were confirmed by complementary analysis of diffusion tensor metrics.

Download Full-text

Co-occurrence of depressive symptoms and executive dysfunction after stroke: associations with brain pathology and prognosis

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2017-317548 ◽

2018 ◽

Vol 89 (8) ◽

pp. 859-865 ◽

Cited By ~ 8

Author(s):

Elles Douven ◽

Pauline Aalten ◽

Julie Staals ◽

Syenna H J Schievink ◽

Robert J van Oostenbrugge ◽

...

Keyword(s):

Depressive Symptoms ◽

White Matter ◽

Disease Burden ◽

Small Vessel Disease ◽

Executive Dysfunction ◽

Cerebral Small Vessel Disease ◽

White Matter Hyperintensity ◽

Brain Pathology ◽

Vessel Disease ◽

Global Brain

ObjectiveTo examine, first, whether the co-occurrence of executive dysfunction (ED) and poststroke depression (PSD) shows different associations with neuroimaging markers and the course of depression and executive function, and second, whether it is associated with a different course on other cognitive domains and quality of life.MethodsThe present study included 245 stroke patients (35.9% female, mean age 67.5 years (SD=11.9). All patients completed neuropsychological and neuropsychiatric assessment 3 months poststroke, which were repeated at 6-month and 12-month follow-up. A subset (n=186) received 3-Tesla brain MRI at baseline to evaluate lesion-related imaging markers, white matter hyperintensity volume, global brain atrophy and total cerebral small vessel disease burden.ResultsPatients with ‘depression–executive dysfunction syndrome’ (DES) showed higher white matter hyperintensity volumes compared with all other groups and more frequently showed left-sided lesions compared with ED only and PSD only. They also had more frequently old infarcts and higher total cerebral small vessel disease burden compared with PSD only and patients with neither ED nor PSD, and more global brain atrophy compared with PSD only. Longitudinal analyses showed that patients with DES had a more chronic course of depressive symptoms relative to PSD only, and a stable pattern of worse cognitive performance similar to patients with ED only.ConclusionsThe co-occurrence of ED and PSD is associated with a worse prognosis of depression, persistent cognitive impairment and a higher amount of vascular and degenerative brain pathology. Future studies are needed to examine whether these patients represent a more severe subtype within the PSD spectrum.Clinical trial registrationNCT02585349;Results.

Download Full-text