18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Relationship between Cortical Blood Flow and Sub-Cortical White-Matter Health across the Adult Age Span

      research-article
      1 , 2 , 3 , * , 2 , 4 , 2 , 3 , 5
      PLoS ONE
      Public Library of Science

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Degeneration of cerebral white matter is commonly observed in aging, and the associated degradation in neural connectivity contributes to cognitive decline in older adults. Vascular dysfunction has been implicated as a potential mechanism for general age-related neural tissue deterioration; however, no prior study has examined the direct relationship between cortical vascular health and subcortical white-matter integrity. In this work, we aimed to determine whether blood supply to the brain is associated with microstructural integrity of connective tissue, and whether such associations are regionally specific and mainly accounted for by aging. We examined the association between cerebral blood flow (CBF) in the cortical mantle, measured using arterial spin labeling (ASL), and subcortical white-matter integrity, measured using diffusion tensor imaging (DTI), in a group of healthy adults spanning early to late adulthood. We found cortical CBF to be significantly associated with white-matter integrity throughout the brain. In addition, these associations were only partially tied to aging, as they remained even when statistically controlling for age, and when restricting the analyses to a young subset of the sample. Furthermore, vascular risk was not a prominent determinant of these effects. These findings suggest that the overall blood supply to the brain is an important indicator of white-matter health in the normal range of variations amongst adults, and that the decline in CBF with advancing age may potentially exacerbate deterioration of the connective anatomy of the brain.

          Related collections

          Most cited references49

          • Record: found
          • Abstract: found
          • Article: not found

          High-resolution intersubject averaging and a coordinate system for the cortical surface.

          The neurons of the human cerebral cortex are arranged in a highly folded sheet, with the majority of the cortical surface area buried in folds. Cortical maps are typically arranged with a topography oriented parallel to the cortical surface. Despite this unambiguous sheetlike geometry, the most commonly used coordinate systems for localizing cortical features are based on 3-D stereotaxic coordinates rather than on position relative to the 2-D cortical sheet. In order to address the need for a more natural surface-based coordinate system for the cortex, we have developed a means for generating an average folding pattern across a large number of individual subjects as a function on the unit sphere and of nonrigidly aligning each individual with the average. This establishes a spherical surface-based coordinate system that is adapted to the folding pattern of each individual subject, allowing for much higher localization accuracy of structural and functional features of the human brain.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            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.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease.

              Vascular dysfunction has a critical role in Alzheimer's disease (AD). Recent data from brain imaging studies in humans and animal models suggest that cerebrovascular dysfunction may precede cognitive decline and onset of neurodegenerative changes in AD and AD models. Cerebral hypoperfusion and impaired amyloid beta-peptide (Abeta) clearance across the blood-brain barrier (BBB) may contribute to the onset and progression of dementia AD type. Decreased cerebral blood flow (CBF) negatively affects the synthesis of proteins required for memory and learning, and may eventually lead to neuritic injury and neuronal death. Impaired clearance of Abeta from the brain by the cells of the neurovascular unit may lead to its accumulation on blood vessels and in brain parenchyma. The accumulation of Abeta on the cerebral blood vessels, known as cerebral amyloid angiopathy (CAA), is associated with cognitive decline and is one of the hallmarks of AD pathology. CAA can severely disrupt the integrity of the blood vessel wall resulting in micro or macro intracerebral bleedings that exacerbates neurodegenerative process and inflammatory response and may lead to hemorrhagic stroke, respectively. Here, we review the role of the neurovascular unit and molecular mechanisms in vascular cells behind AD and CAA pathogenesis. First, we discuss apparent vascular changes, including the cerebral hypoperfusion and vascular degeneration that contribute to different stages of the disease process in AD individuals. We next discuss the role of the low-density lipoprotein receptor related protein-1 (LRP), a key Abeta clearance receptor at the BBB and along the cerebrovascular system, whose expression is suppressed early in AD. We also discuss how brain-derived apolipoprotein E isoforms may influence Abeta clearance across the BBB. We then review the role of two interacting transcription factors, myocardin and serum response factor, in cerebral vascular cells in controlling CBF responses and LRP-mediated Abeta clearance. Finally, we discuss the role of microglia and perivascular macrophages in Abeta clearance from the brain. The data reviewed here support an essential role of neurovascular and BBB mechanisms in contributing to both, onset and progression of AD.
                Bookmark

                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
                21 February 2013
                : 8
                : 2
                : e56733
                Affiliations
                [1 ]Rotman Research Institute, Baycrest Centre for Geriatric Care, University of Toronto, Toronto, Canada
                [2 ]Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
                [3 ]Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
                [4 ]Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
                [5 ]Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, Massachusetts, United States of America
                Université de Montréal, Canada
                Author notes

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

                Conceived and designed the experiments: JJC DHS. Performed the experiments: HDR DHS. Analyzed the data: JJC. Contributed reagents/materials/analysis tools: JJC. Wrote the paper: JJC DHS.

                Article
                PONE-D-12-33274
                10.1371/journal.pone.0056733
                3578934
                23437228
                0f190ac8-5f48-4cc8-bc69-b4166a360725
                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
                : 29 October 2012
                : 14 January 2013
                Page count
                Pages: 12
                Funding
                This research was supported by National Institutes of Health grants R01NR010827, NS042861, and P41RR14075, as well as by fellowship funding from the Canadian Institutes of Health Research (to JJC) and the Athinoula A. Martinos Center for Biomedical Imaging. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Neurological System
                Neuroanatomy
                Physiological Processes
                Aging
                Biophysics
                Developmental Biology
                Organism Development
                Aging
                Neuroscience
                Neuroanatomy
                Systems Biology
                Medicine
                Anatomy and Physiology
                Neurological System
                Neuroanatomy
                Physiological Processes
                Aging
                Geriatrics
                Neurology
                Neuroimaging

                Uncategorized
                Uncategorized

                Comments

                Comment on this article