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      Ageing and brain white matter structure in 3,513 UK Biobank participants

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          Abstract

          Quantifying the microstructural properties of the human brain's connections is necessary for understanding normal ageing and disease. Here we examine brain white matter magnetic resonance imaging (MRI) data in 3,513 generally healthy people aged 44.64–77.12 years from the UK Biobank. Using conventional water diffusion measures and newer, rarely studied indices from neurite orientation dispersion and density imaging, we document large age associations with white matter microstructure. Mean diffusivity is the most age-sensitive measure, with negative age associations strongest in the thalamic radiation and association fibres. White matter microstructure across brain tracts becomes increasingly correlated in older age. This may reflect an age-related aggregation of systemic detrimental effects. We report several other novel results, including age associations with hemisphere and sex, and comparative volumetric MRI analyses. Results from this unusually large, single-scanner sample provide one of the most extensive characterizations of age associations with major white matter tracts in the human brain.

          Abstract

          Part of understanding ageing involves knowing how the brain's connecting pathways change in healthy aging. Here, authors provide a detailed characterisation of data from 3513 UK Biobank participants, and show that the microstructure of these pathways becomes more similar with age.

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          Most cited references43

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          Life-span changes of the human brain white matter: diffusion tensor imaging (DTI) and volumetry.

          Magnetic resonance imaging volumetry studies report inverted U-patterns with increasing white-matter (WM) volume into middle age suggesting protracted WM maturation compared with the cortical gray matter. Diffusion tensor imaging (DTI) is sensitive to degree and direction of water permeability in biological tissues, providing in vivo indices of WM microstructure. The aim of this cross-sectional study was to delineate age trajectories of WM volume and DTI indices in 430 healthy subjects ranging 8-85 years of age. We used automated regional brain volume segmentation and tract-based statistics of fractional anisotropy, mean, and radial diffusivity as markers of WM integrity. Nonparametric regressions were used to fit the age trajectories and to estimate the timing of maximum development and deterioration in aging. Although the volumetric data supported protracted growth into the sixth decade, DTI indices plateaued early in the fourth decade across all tested regions and then declined slowly into late adulthood followed by an accelerating decrease in senescence. Tractwise and voxel-based analyses yielded regional differences in development and aging but did not provide ample evidence in support of a simple last-in-first-out hypothesis of life-span changes.
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            The evolution of distributed association networks in the human brain.

            The human cerebral cortex is vastly expanded relative to other primates and disproportionately occupied by distributed association regions. Here we offer a hypothesis about how association networks evolved their prominence and came to possess circuit properties vital to human cognition. The rapid expansion of the cortical mantle may have untethered large portions of the cortex from strong constraints of molecular gradients and early activity cascades that lead to sensory hierarchies. What fill the gaps between these hierarchies are densely interconnected networks that widely span the cortex and mature late into development. Limitations of the tethering hypothesis are discussed as well as its broad implications for understanding critical features of the human brain as a byproduct of size scaling. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Lifespan maturation and degeneration of human brain white matter

              Properties of human brain tissue change across the lifespan. Here we model these changes in the living human brain by combining quantitative MRI measurements of R1 (1/T1) with diffusion MRI and tractography (N=102, ages 7–85). The amount of R1 change during development differs between white matter fascicles, but in each fascicle the rate of development and decline are mirror symmetric; the rate of R1 development as the brain approaches maturity predicts the rate of R1 degeneration in aging. Quantitative measurements of macromolecule tissue volume (MTV) confirm that R1 is an accurate index of the growth of new brain tissue. In contrast to R1, diffusion development follows an asymmetric time-course with rapid childhood changes but a slow rate of decline in old age. Together, the time-courses of R1 and diffusion changes demonstrate that multiple biological processes drive changes in white matter tissue properties over the lifespan.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group
                2041-1723
                15 December 2016
                2016
                : 7
                : 13629
                Affiliations
                [1 ]Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh , Edinburgh EH8 9JZ, UK
                [2 ]Department of Psychology, University of Edinburgh , Edinburgh EH8 9JZ, UK
                [3 ]Scottish Imaging Network, a Platform for Scientific Excellence (SINAPSE) Collaboration , Edinburgh EH8 9JZ, UK
                [4 ]Department of Psychology, University of Texas , Austin, Texas 78712-0187, USA
                [5 ]Division of Psychiatry, University of Edinburgh , Edinburgh EH10 5HF, UK
                [6 ]Brain Research Imaging Centre, Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh , Edinburgh EH4 2XU, UK
                [7 ]MRC Lifecourse Epidemiology Unit, University of Southampton , Southampton SO17 1BJ, UK
                Author notes
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0003-4036-3642
                http://orcid.org/0000-0002-0544-7368
                http://orcid.org/0000-0002-9812-6642
                Article
                ncomms13629
                10.1038/ncomms13629
                5172385
                27976682
                0aa2efbd-0442-4f11-aadb-e74111612f0d
                Copyright © 2016, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 17 August 2016
                : 18 October 2016
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