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      Systemic Inflammation in Non-Demented Elderly Human Subjects: Brain Microstructure and Cognition

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          Abstract

          The purpose of this study was to test the hypothesis that higher levels of systemic inflammation in a community sample of non-demented subjects older than seventy years of age are associated with reduced diffusion anisotropy in brain white matter and lower cognition. Ninety-five older persons without dementia underwent detailed clinical and cognitive evaluation and magnetic resonance imaging, including diffusion tensor imaging. Systemic inflammation was assessed with a composite measure of commonly used circulating inflammatory markers (C-reactive protein and tumor necrosis factor-alpha). Tract-based spatial statistics analyses demonstrated that diffusion anisotropy in the body and isthmus of the corpus callosum was negatively correlated with the composite measure of systemic inflammation, controlling for demographic, clinical and radiologic factors. Visuospatial ability was negatively correlated with systemic inflammation, and diffusion anisotropy in the body and isthmus of the corpus callosum was shown to mediate this association. The findings of the present study suggest that higher levels of systemic inflammation may be associated with lower microstructural integrity in the corpus callosum of non-demented elderly individuals, and this may partially explain the finding of reduced higher-order visual cognition in aging.

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          Overview and findings from the rush Memory and Aging Project.

          The Memory and Aging Project is a longitudinal, epidemiologic clinical-pathologic cohort study of common chronic conditions of aging with an emphasis on decline in cognitive and motor function and risk of Alzheimer's disease (AD). In this manuscript, we first summarize the study design and methods. Then, we present data on: (1) the relation of motor function to cognition, disability, and death; (2) the relation of risk factors to cognitive and motor outcomes, disability and death; (3) the relation of neuropathologic indices to cognitive outcomes; (4) the relation of risk factors to neuropathologic indices; and (5) additional study findings. The findings are discussed and contextualized.
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            Topography of the human corpus callosum revisited--comprehensive fiber tractography using diffusion tensor magnetic resonance imaging.

            Several tracing studies have established a topographical distribution of fiber connections to the cortex in midsagittal cross-sections of the corpus callosum (CC). The most prominent example is Witelson's scheme, which defines five vertical partitions mainly based on primate data. Conventional MRI of the human CC does not reveal morphologically discernable structures, although microscopy techniques identified myelinated axons with a relatively small diameter in the anterior and posterior third of the CC as opposed to thick fibers in the midbody and posterior splenium. Here, we applied diffusion tensor imaging (DTI) in conjunction with a tract-tracing algorithm to gain cortical connectivity information of the CC in individual subjects. With DTI-based tractography, we distinguished five vertical segments of the CC, containing fibers projecting into prefrontal, premotor (and supplementary motor), primary motor, and primary sensory areas as well as into parietal, temporal, and occipital cortical areas. Striking differences to Witelson's classification were recognized in the midbody and anterior third of the CC. In particular, callosal motor fiber bundles were found to cross the CC in a much more posterior location than previously indicated. Differences in water mobility were found to be in qualitative agreement with differences in the microstructure of transcallosal fibers yielding the highest anisotropy in posterior regions of the CC. The lowest anisotropy was observed in compartments assigned to motor and sensory cortical areas. In conclusion, DTI-based fiber tractography of healthy human subjects suggests a modification of the widely accepted Witelson scheme and a new classification of vertical CC partitions.
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              Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty.

              Interleukin-6 (IL-6) is a proinflammatory cytokine that is normally tightly regulated and expressed at low levels, except during infection, trauma, or other stress. Among several factors that down-regulate IL-6 gene expression are estrogen and testosterone. After menopause or andropause, IL-6 levels are elevated, even in the absence of infection, trauma, or stress. IL-6 is a potent mediator of inflammatory processes, and it has been proposed that the age-associated increase in IL-6 accounts for certain of the phenotypic changes of advanced age, particularly those that resemble chronic inflammatory disease [decreased lean body mass, osteopenia, low-grade anemia, decreased serum albumin and cholesterol, and increased inflammatory proteins such as C-reactive protein (CRP) and serum amyloid A]. Furthermore, the age-associated rise in IL-6 has been linked to lymphoproliferative disorders, multiple myeloma, osteoporosis, and Alzheimer's disease. This overview discusses the data relating IL-6 to age-associated diseases and to frailty. Like the syndrome of inappropriate antidiuretic hormone, it is possible that certain clinically important late-life changes are due to an inappropriate presence of IL-6.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                26 August 2013
                : 8
                : 8
                : e73107
                Affiliations
                [1 ]Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, United States of America
                [2 ]Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States of America
                [3 ]Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, Illinois, United States of America
                [4 ]Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, United States of America
                [5 ]Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, United States of America
                [6 ]Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, United States of America
                Northwestern University Feinberg School of Medicine, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: KA DAF MCM LLB DAB. Analyzed the data: GG CMB AV. Wrote the paper: KA.

                Article
                PONE-D-13-25315
                10.1371/journal.pone.0073107
                3753267
                23991174
                157dcc9b-a933-4f79-8674-9d7722f0b71a
                Copyright @ 2013

                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 the original author and source are credited.

                History
                : 18 June 2013
                : 24 July 2013
                Page count
                Pages: 8
                Funding
                Support provided by: National Institute on Aging (NIA) grants R01AG17917, R01AG2448; National Institute of Minority Health and Health Disparities (NHMHD) P20MD6886; Alzheimer's Association grant IIRG-07-59818; National Institute of Biomedical Imaging and Bioengineering (NIBIB) grants R21EB005273, R21EB006525; National Institute of Neurological Disorders and Stroke grant R21NS076827; Rush Translational Science Consortium; Pritzker Institute of Biomedical Science and Engineering; Marsha K. Dowd Philanthropic Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Biochemistry
                Proteins
                C-Reactive Proteins
                Immunology
                Immunity
                Inflammation
                Microbiology
                Immunity
                Inflammation
                Population Biology
                Epidemiology
                Epidemiology of Aging
                Medicine
                Clinical Immunology
                Immunity
                Inflammation
                Clinical Research Design
                Epidemiology
                Epidemiology
                Epidemiology of Aging
                Neurology
                Neuroimaging
                Radiology
                Diagnostic Radiology
                Magnetic Resonance Imaging

                Uncategorized
                Uncategorized

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