Abstract 13193: Association of Abnormal P-wave Indices With Brain MRI Infarcts: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jorge L Reyes ◽  
Faye L Norby ◽  
Wendy Wang ◽  
Romil Parikh ◽  
Niki C Oldenburg ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Brain Mri ◽  
P Wave ◽  
Small Vessel ◽  
Silent Ischemia ◽  
Lacunar Infarcts ◽  
Vessel Disease ◽  
Increased Risk ◽  
Mri Scans ◽  
Multivariable Adjustment

Introduction: We recently reported that abnormal P-wave indices (PWI)—ECG markers of atrial cardiomyopathy (AC)—are associated with an increased risk of dementia, independent of atrial fibrillation (AF) and clinical ischemic stroke. The mechanisms, however, remain unclear, but may include silent ischemia. Hypothesis: Abnormal PWI are associated with higher prevalence of cortical infarcts on MRI, suggesting cardioembolism as a potential mechanism. Methods: ARIC-NCS participants (mean age, 72.2±5.3 years; 60% women; 29% black) who underwent 3T brain MRI scans in 2011-2013 were included. Abnormal PWI included P-wave terminal force in lead V1 [(PTFV1) defined as ≥4000 μV*ms] and P-wave duration [(PWD) defined as >120 ms], which were measured from standard 12-lead ECGs. Brain MRI outcomes included cortical infarcts, cerebral microbleeds (CMB), and markers of small vessel disease [white matter hyperintensities (WMH) and lacunar infarcts]. We used weighted multivariable logistic and linear regression analyses. Results: Of the 1,850 participants, 464 had abnormal PTFV1 and 415 had prolonged PWD. After multivariable adjustment including AF, abnormal PTFV1 and PWD were significantly associated with 26-44% increased odds of cortical and lacunar infarcts (Table) . Although PWD was associated with CMB in Model 1, the association was no longer significant after multivariable adjustment. Finally, abnormal PWIs were not associated with WMH after adjusting for stroke and AF (P >0.5). Conclusions: Abnormal PWI are associated with higher prevalence of cortical infarcts, suggesting cardioembolism with silent ischemia as a possible mechanism underlying the association of AC with dementia. More research is needed to evaluate other mechanisms such as cerebral small vessel disease.

scholarly journals Vascular brain pathology is more important than neurodegeneration in pathogenesis of pre-stroke cognitive impairment

2020 ◽  
Author(s):  
T Schellhorn ◽  
M Zucknick ◽  
T Askim ◽  
R Munthe-Kaas ◽  
H Ihle-Hansen ◽  
...  
Keyword(s):  
Gender Differences ◽  
Cognitive Impairment ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Small Vessel ◽  
Brain Pathology ◽  
Cerebrovascular Pathology ◽  
Vessel Disease ◽  
Increased Risk ◽  
Prospective Longitudinal

AbstractIntroductionTo better understand the development of post-stroke cognitive impairment,we explored the association between pre-stroke neuroimaging features and pre-stroke cognitive impairment and investigated possible gender differences. Few previous studies on this topic have been performed.MethodsIn this large prospective longitudinal multicenter brain-MRI cohort study, patients admitted to five stroke units at five different Norwegian hospitals were recruited as part of the Norwegian cognitive impairment after stroke study. Visual radiological assessment of small vessel disease and neurodegenerative changes were performed on brain MRI from 410 patients. Pre-stroke cognition was assessed using the Global Deterioration Scale.ResultsAt least one pathological marker was found in 68% of the patients. The mean age (SD) of the patients with no pathological changes other than the acute stroke, was 70 (± 12.9) and 75 (± 10.2) years for those with pathological scans (p ≤ 0.001). Men were more likely to have at least one pathological brain MRI finding, lacunes, or pathological medial temporal lobe atrophy. The highest percentage of patients with a pathological pre-stroke GDS were found in the “cerebrovascular pathology” group (37.5%) and in the “mixed pathology”-group (44%). In these groups, both men and women had an increased risk of impaired pre-stroke cognition.ConclusionThe majority of patients showed preexisting structural brain pathology. Cerebrovascular pathology was the dominating imaging finding associated with cognitive impairment, thus indicating that the pathogenesis of pre-stroke cognitive impairment might be driven more by small vessel disease (SVD) than neurodegenerative changes. Gender differences exists, with less pathology in women.

scholarly journals Broad phenotype of cysteine-altering NOTCH3 variants in UK Biobank

Neurology ◽  
2020 ◽  
Vol 95 (13) ◽  
pp. e1835-e1843 ◽  
Author(s):  
Julie W. Rutten ◽  
Remco J. Hack ◽  
Marco Duering ◽  
Gido Gravesteijn ◽  
Johannes G. Dauwerse ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Brain Mri ◽  
Clinical Information ◽  
Community Dwelling ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Uk Biobank ◽  
Vessel Disease ◽  
Healthy Elderly ◽  
Increased Risk

ObjectiveTo determine the small vessel disease spectrum associated with cysteine-altering NOTCH3 variants in community-dwelling individuals by analyzing the clinical and neuroimaging features of UK Biobank participants harboring such variants.MethodsThe exome and genome sequencing datasets of the UK Biobank (n = 50,000) and cohorts of cognitively healthy elderly (n = 751) were queried for cysteine-altering NOTCH3 variants. Brain MRIs of individuals harboring such variants were scored according to Standards for Reporting Vascular Changes on Neuroimaging criteria, and clinical information was extracted with ICD-10 codes. Clinical and neuroimaging data were compared to age- and sex-matched UK Biobank controls and clinically diagnosed patients from the Dutch cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) registry.ResultsWe identified 108 individuals harboring a cysteine-altering NOTCH3 variant (2.2 of 1,000), of whom 75% have a variant that has previously been reported in CADASIL pedigrees. Almost all variants were located in 1 of the NOTCH3 protein epidermal growth factor–like repeat domains 7 to 34. White matter hyperintensity lesion load was higher in individuals with NOTCH3 variants than in controls (p = 0.006) but lower than in patients with CADASIL with the same variants (p < 0.001). Almost half of the 24 individuals with brain MRI had a Fazekas score of 0 or 1 up to age 70 years. There was no increased risk of stroke.ConclusionsAlthough community-dwelling individuals harboring a cysteine-altering NOTCH3 variant have a higher small vessel disease MRI burden than controls, almost half have no MRI abnormalities up to age 70 years. This shows that NOTCH3 cysteine altering variants are associated with an extremely broad phenotypic spectrum, ranging from CADASIL to nonpenetrance.

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

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.

Brain MRI in Monogenic Cerebral Small Vessel Diseases: A Practical Handbook

2021 ◽  
Vol 21 ◽  
Author(s):  
Leonardo Ulivi ◽  
Mirco Cosottini ◽  
Gianmichele Migaleddu ◽  
Giovanni Orlandi ◽  
Nicola Giannini ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Next Generation Sequencing ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Next Generation ◽  
Vessel Disease ◽  
Generation Sequencing ◽  
Cerebral Small Vessel Diseases

: 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.

Abstract 01: Retinal Microvascular Signs and White Matter MRI Findings: The Atherosclerosis Risk in Communities Neurocognitive Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Jennifer A Deal ◽  
Melinda C Power ◽  
Karen Bandeen-Roche ◽  
Michael Griswold ◽  
David Knopman ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
White Matter ◽  
Magnetic Resonance ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Fundus Photography ◽  
Resonance Imaging ◽  
Lacunar Infarcts ◽  
Vessel Disease ◽  
Arteriolar Narrowing

Introduction: Cerebrovascular small vessel disease, seen on brain imaging as lacunes and white matter hyperintensities (WMH), is a substrate for dementia in older adults. Diffusion tensor imaging (DTI) is thought to provide early signs of loss of white matter (WM) integrity due to microvascular disease and predicts WM hyperintensity volume. Retinal fundus photography provides surrogate measures of cerebral microvasculature. No studies have quantified the long-term association between retinal signs and DTI measures. Hypothesis: Microvascular retinal signs measured in midlife are associated with small vessel disease measured on brain magnetic resonance imaging (MRI) 18 years later, including reduced WM microstructural integrity (lower fractional anisotrophy [FA] and greater mean diffusivity [MD] by DTI), greater WM hyperintensity volume and greater lacune prevalence. Methods: In a biracial prospective cohort study, retinal signs were measured using fundus photography (1993-1995) with 3-T magnetic resonance imaging conducted in 2011-13. Multivariable-adjusted linear regression was used to quantify the relationships of retinal signs with WM measures. Prevalence of lacunar infarcts by retinal sign status was estimated using log binomial regression. Analyses were adjusted for age [linear and quadratic terms], education, sex, race, intracranial volume, body mass index, smoking, diabetes, hypertension, and ≥1 APOE ε4 alleles. Results: In 1829 men and women (60% [N=1100] female, 27% [N=489] black race, aged 50-72 years when retinal signs were measured), a binary measure comprised of two retinal signs suggestive of arteriolar damage due to hypertension (focal arteriolar narrowing and/or arteriovenous nicking) was associated with worse (lower) FA (standardized β=-0.19, 95% confidence interval [CI]=-0.35, -0.02), worse (higher) MD (β=0.15, 95% CI=0.00, 0.30), greater WM hyperintensity volume (β=0.15, 95% CI=0.01, 0.30), and greater prevalence of lacunes (prevalence ratio=1.33, 95% CI: 0.99, 1.80). Generalized arteriolar narrowing, measured as the central retinal arteriolar equivalent (CRAE, narrowest quartile vs. widest three quartiles) was associated with worse FA (β=-0.13, 95% CI=-0.24, -0.01) and worse MD (β=0.12, 95% CI=0.01, 0.23). Results did not differ by sex, race, hypertension status or APOE ε4 genotype. No associations were found for retinopathy, but only 56 participants had retinopathy. Conclusions: Consistent with prior work, and as expected based on a common underlying pathology, retinal signs predicted WM disease and lacunar infarcts 18 years later. Novel to this study, we found that retinal signs related to arteriolar damage also predicted loss of white matter microvascular integrity measured using DTI.

scholarly journals Relationship Between Step Counts and Cerebral Small Vessel Disease in Japanese Men

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3584-3591
Author(s):  
Mohammad Moniruzzaman ◽  
Aya Kadota ◽  
Hiroyoshi Segawa ◽  
Keiko Kondo ◽  
Sayuki Torii ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Cerebral Microbleeds ◽  
Small Vessel ◽  
Odds Ratios ◽  
Japanese Men ◽  
Lacunar Infarcts ◽  
Step Counts ◽  
Vessel Disease ◽  
Steps Per Day

Background and Purpose: Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population. Methods: We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006–2008) using a pedometer. CSVD was assessed at follow-ups (2012–2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression. Results: Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175–10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30–0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29–0.86]), and lacunar infarcts (0.52 [95% CI, 0.30–0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors. Conclusions: We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.

scholarly journals Cerebrospinal Fluid Metals and the Association with Cerebral Small Vessel Disease

2020 ◽  
Vol 78 (3) ◽  
pp. 1229-1236
Author(s):  
Mana Shams ◽  
Juha Martola ◽  
Andreas Charidimou ◽  
Tobias Granberg ◽  
Daniel Ferreira ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Serum Albumin ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Microbleeds ◽  
Small Vessel ◽  
Vessel Disease ◽  
Significant Difference ◽  
Metal Levels ◽  
T Tau

Background: Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma. Objective: Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels. Methods: This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-β (Aβ) 42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models. Results: No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aβ42, T-tau, P-tau, and CSF/serum albumin ratios (p < 0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOE ɛ4 carriers. Conclusion: CSF iron levels are elevated with cerebral microbleeds in APOE ɛ4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients.

scholarly journals Consensus statement for diagnosis of subcortical small vessel disease

2015 ◽  
Vol 36 (1) ◽  
pp. 6-25 ◽  
Author(s):  
Gary A Rosenberg ◽  
Anders Wallin ◽  
Joanna M Wardlaw ◽  
Hugh S Markus ◽  
Joan Montaner ◽  
...  
Keyword(s):  
White Matter ◽  
Consensus Statement ◽  
Small Vessel Disease ◽  
Hereditary Diseases ◽  
Small Vessel ◽  
Progressive Damage ◽  
Lacunar Infarcts ◽  
Vessel Disease ◽  
Binswanger’S Disease ◽  
Binswanger's Disease

Vascular cognitive impairment (VCI) is the diagnostic term used to describe a heterogeneous group of sporadic and hereditary diseases of the large and small blood vessels. Subcortical small vessel disease (SVD) leads to lacunar infarcts and progressive damage to the white matter. Patients with progressive damage to the white matter, referred to as Binswanger’s disease (BD), constitute a spectrum from pure vascular disease to a mixture with neurodegenerative changes. Binswanger’s disease patients are a relatively homogeneous subgroup with hypoxic hypoperfusion, lacunar infarcts, and inflammation that act synergistically to disrupt the blood–brain barrier (BBB) and break down myelin. Identification of this subgroup can be facilitated by multimodal disease markers obtained from clinical, cerebrospinal fluid, neuropsychological, and imaging studies. This consensus statement identifies a potential set of biomarkers based on underlying pathologic changes that could facilitate diagnosis and aid patient selection for future collaborative treatment trials.

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