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

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          Abstract

          The relationship between fibrinogen and white matter hyperintensities (WMHs) are inconsistent. Whether there are different relationships between WMHs and fibrinogen in disparate subtypes of cerebral small vessel disease (CSVD) remains unknown. Here, we investigated the roles of plasma fibrinogen in sporadic CSVD (sCSVD) and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients. We performed a cross-sectional study that included 74 CSVD patients (19 CADASIL and 55 sporadic) and 74 age- and gender-matched healthy controls (HCs). Plasma fibrinogen was determined, and the severity of WMHs in CSVD patients was rated according to Fazekas scales. Univariate analysis and ordinal logistic regression were performed to evaluate the relationship between fibrinogen and the severity of WMHs in CSVD. Both CADASIL and sCSVD patients showed significantly higher plasma fibrinogen levels than HCs. No significant difference in the plasma fibrinogen level was observed between CADASIL and sCSVD. Univariate analysis and ordinal logistic regression indicated that fibrinogen is an independent risk factor for the severity of WMHs in CADASIL patients (odds ratio [OR] =1.064; 95% Confidence interval (CI, 1.004-1.127); p =0.037). However, age (odds ratio [OR] =1.093; 95% CI (1.033-1.156); P = 0.002), but not fibrinogen (odds ratio [OR] =1.004; 95% CI (0.997-1.011); P=0.262), is an independent risk factor for the severity of WMHs in sCSVD patients. Our results suggest that high levels of plasma fibrinogen are associated with the severity of WMHs in CADASIL but not in sCSVD patients, indicating that the role of fibrinogen may be different in disparate subtypes of CSVD. A better understanding of fibrinogen may yield insights into the pathogenesis of CSVD.

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          Most cited references44

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          Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration

          Summary Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).
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            Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges.

            The term cerebral small vessel disease refers to a group of pathological processes with various aetiologies that affect the small arteries, arterioles, venules, and capillaries of the brain. Age-related and hypertension-related small vessel diseases and cerebral amyloid angiopathy are the most common forms. The consequences of small vessel disease on the brain parenchyma are mainly lesions located in the subcortical structures such as lacunar infarcts, white matter lesions, large haemorrhages, and microbleeds. Because lacunar infarcts and white matter lesions are easily detected by neuroimaging, whereas small vessels are not, the term small vessel disease is frequently used to describe the parenchyma lesions rather than the underlying small vessel alterations. This classification, however, restricts the definition of small vessel disease to ischaemic lesions and might be misleading. Small vessel disease has an important role in cerebrovascular disease and is a leading cause of cognitive decline and functional loss in the elderly. Small vessel disease should be a main target for preventive and treatment strategies, but all types of presentation and complications should be taken into account. Copyright 2010 Elsevier Ltd. All rights reserved.
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              ROCR: visualizing classifier performance in R.

              ROCR is a package for evaluating and visualizing the performance of scoring classifiers in the statistical language R. It features over 25 performance measures that can be freely combined to create two-dimensional performance curves. Standard methods for investigating trade-offs between specific performance measures are available within a uniform framework, including receiver operating characteristic (ROC) graphs, precision/recall plots, lift charts and cost curves. ROCR integrates tightly with R's powerful graphics capabilities, thus allowing for highly adjustable plots. Being equipped with only three commands and reasonable default values for optional parameters, ROCR combines flexibility with ease of usage. http://rocr.bioinf.mpi-sb.mpg.de. ROCR can be used under the terms of the GNU General Public License. Running within R, it is platform-independent. tobias.sing@mpi-sb.mpg.de.
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                Author and article information

                Journal
                Aging Dis
                Aging Dis
                Aging and Disease
                JKL International LLC
                2152-5250
                June 2021
                1 June 2021
                : 12
                : 3
                : 801-811
                Affiliations
                [1-ad-12-3-801] 1Department of Neurology, Zhujiang Hospital of Southern Medical University, Guangdong 510282, China.
                [2-ad-12-3-801] 2Department of Radiology, Zhujiang Hospital of Southern Medical University, Guangdong 510282, China.
                [3-ad-12-3-801] 3School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
                [4-ad-12-3-801] 4School of Medicine, Sun Yat-sen University, Guangzhou, Guangzhou 510515, China.
                [5-ad-12-3-801] 5Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
                [6-ad-12-3-801] 6Department of Neurology, University of California, San Francisco & the San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
                Author notes
                [* ]Correspondence should be addressed to: Dr. Qing Wang (Email: denniswq@ 123456yahoo.com ), or Dr. Shuzhen Zhu (Email: 453951712@ 123456qq.com ), Zhujiang Hospital of Southern Medical University, Guangdong 510282, China.
                [#]

                these authors contributed equally.

                Article
                ad-12-3-801
                10.14336/AD.2020.1110
                8139197
                34094643
                6fc71ded-9b35-42ea-8834-f4898e4b82d8
                copyright: © 2021 Guo et al.

                this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 23 September 2020
                : 8 November 2020
                : 10 November 2020
                Categories
                Orginal Article

                fibrinogen,cadasil,cerebral small vessel disease,white matter hyperintensities

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