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      Cerebral microbleeds: overview and implications in cognitive impairment

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          Abstract

          Cerebral microbleeds (MBs) are small chronic brain hemorrhages which are likely caused by structural abnormalities of the small vessels of the brain. Owing to the paramagnetic properties of blood degradation products, MBs can be detected in vivo by using specific magnetic resonance imaging (MRI) sequences. Over the last decades, the implementation of these MRI sequences in both epidemiological and clinical studies has revealed MBs as a common finding in many different populations, including healthy individuals. Also, the topographic distribution of these MBs has been shown to be potentially associated with specific underlying vasculopathies. However, the clinical and prognostic significance of these small hemorrhages is still a matter of debate as well as a focus of extensive research. In this article, we aim to review the current knowledge on the pathophysiology and clinical implications of MBs, with special emphasis on the links between lobar MBs, cerebral amyloid angiopathy, and Alzheimer’s disease.

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          Most cited references53

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          Susceptibility weighted imaging (SWI).

          Susceptibility differences between tissues can be utilized as a new type of contrast in MRI that is different from spin density, T1-, or T2-weighted imaging. Signals from substances with different magnetic susceptibilities compared to their neighboring tissue will become out of phase with these tissues at sufficiently long echo times (TEs). Thus, phase imaging offers a means of enhancing contrast in MRI. Specifically, the phase images themselves can provide excellent contrast between gray matter (GM) and white matter (WM), iron-laden tissues, venous blood vessels, and other tissues with susceptibilities that are different from the background tissue. Also, for the first time, projection phase images are shown to demonstrate tissue (vessel) continuity. In this work, the best approach for combining magnitude and phase images is discussed. The phase images are high-pass-filtered and then transformed to a special phase mask that varies in amplitude between zero and unity. This mask is multiplied a few times into the original magnitude image to create enhanced contrast between tissues with different susceptibilities. For this reason, this method is referred to as susceptibility-weighted imaging (SWI). Mathematical arguments are presented to determine the number of phase mask multiplications that should take place. Examples are given for enhancing GM/WM contrast and water/fat contrast, identifying brain iron, and visualizing veins in the brain. Copyright 2004 Wiley-Liss, Inc.
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            Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report.

            Amyloid-beta peptide (Abeta) has a key role in the pathogenesis of Alzheimer disease (AD). Immunization with Abeta in a transgenic mouse model of AD reduces both age-related accumulation of Abeta in the brain and associated cognitive impairment. Here we present the first analysis of human neuropathology after immunization with Abeta (AN-1792). Comparison with unimmunized cases of AD (n = 7) revealed the following unusual features in the immunized case, despite diagnostic neuropathological features of AD: (i) there were extensive areas of neocortex with very few Abeta plaques; (ii) those areas of cortex that were devoid of Abeta plaques contained densities of tangles, neuropil threads and cerebral amyloid angiopathy (CAA) similar to unimmunized AD, but lacked plaque-associated dystrophic neurites and astrocyte clusters; (iii) in some regions devoid of plaques, Abeta-immunoreactivity was associated with microglia; (iv) T-lymphocyte meningoencephalitis was present; and (v) cerebral white matter showed infiltration by macrophages. Findings (i)-(iii) strongly resemble the changes seen after Abeta immunotherapy in mouse models of AD and suggest that the immune response generated against the peptide elicited clearance of Abeta plaques in this patient. The T-lymphocyte meningoencephalitis is likely to correspond to the side effect seen in some other patients who received AN-1792 (refs. 7-9).
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              Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study.

              Cerebral microbleeds are focal deposits of hemosiderin that can be visualized with MRI. Little is known on their prevalence in the general population and on their etiology. It has been suggested that, in analogy to spontaneous intracranial hemorrhage, the etiology of microbleeds differs according to their location in the brain, with lobar microbleeds being caused by cerebral amyloid angiopathy and deep or infratentorial microbleeds resulting from hypertension and atherosclerosis. We investigated the prevalence of and risk factors for microbleeds in the general population aged 60 years and older. This study is based on 1,062 persons (mean age 69.6 years) from the population-based Rotterdam Scan Study. MRI was performed at 1.5 T and included a sequence optimized to increase the conspicuity of microbleeds. We assessed the relation of APOE genotype, cardiovascular risk factors, and markers of small vessel disease to the presence and location of microbleeds with multiple logistic regression. Overall prevalence of cerebral microbleeds was high and increased with age from 17.8% in persons aged 60-69 years to 38.3% in those over 80 years. APOE epsilon 4 carriers had significantly more often strictly lobar microbleeds than noncarriers. In contrast, cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location but not in a lobar location. The prevalence of cerebral microbleeds is high. Our data support the hypothesis that strictly lobar microbleeds are related to cerebral amyloid angiopathy, whereas microbleeds in a deep or infratentorial location result from hypertensive or atherosclerotic microangiopathy.
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                Author and article information

                Contributors
                Journal
                Alzheimers Res Ther
                Alzheimers Res Ther
                Alzheimer's Research & Therapy
                BioMed Central
                1758-9193
                2014
                11 June 2014
                : 6
                : 3
                : 33
                Affiliations
                [1 ]Philip J. Kistler Stroke Research Center, Massachusetts General Hospital, 175 Cambridge Street Suite 300, Boston, MA 02114, USA
                Article
                alzrt263
                10.1186/alzrt263
                4075149
                24987468
                6a5d2822-f0d8-44eb-b2e4-4a145e2a9eb9
                Copyright © 2014 Martinez-Ramirez et al.; licensee BioMed Central Ltd.

                The licensee has exclusive rights to distribute this article, in any medium, for [6/12] months following its publication. After this time, the article is available under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0) applies to the data made available in this article, unless otherwise stated.

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                Neurology
                Neurology

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