title: Widespread age-related differences in the human brain microstructure revealed by quantitative magnetic resonance imaging.
abstract: A pressing need exists to disentangle age-related changes from pathologic neurodegeneration. This study aims to characterize the spatial pattern and age-related differences of biologically relevant measures in vivo over the course of normal aging. Quantitative multiparameter maps that provide neuroimaging biomarkers for myelination and iron levels, parameters sensitive to aging, were acquired from 138 healthy volunteers (age range: 19-75 years). Whole-brain voxel-wise analysis revealed a global pattern of age-related degeneration. Significant demyelination occurred principally in the white matter. The observed age-related differences in myelination were anatomically specific. In line with invasive histologic reports, higher age-related differences were seen in the genu of the corpus callosum than the splenium. Iron levels were significantly increased in the basal ganglia, red nucleus, and extensive cortical regions but decreased along the superior occipitofrontal fascicle and optic radiation. This whole-brain pattern of age-associated microstructural differences in the asymptomatic population provides insight into the neurobiology of aging. The results help build a quantitative baseline from which to examine and draw a dividing line between healthy aging and pathologic neurodegeneration.
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, UK. Electronic address: m.callaghan@ucl.ac.uk.
authors.forename: Martina F
authors.initials: MF
authors.lastname: Callaghan
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, UK; Spinal Cord Injury Center Balgrist, University Hospital Zurich, Zurich, Switzerland; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Freund
authors.affiliation: Department des Neurosciences Cliniques, LREN, CHUV, Universite de Lausanne, Lausanne, Switzerland.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Draganski
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Anderson
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, UK; Psychology Department, Goldsmiths College, University of London, London, UK.
authors.forename: Marinella
authors.initials: M
authors.lastname: Cappelletti
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, UK.
authors.forename: Rumana
authors.initials: R
authors.lastname: Chowdhury
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, UK.
authors.forename: Joern
authors.initials: J
authors.lastname: Diedrichsen
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, UK.
authors.forename: Thomas H B
authors.initials: TH
authors.lastname: Fitzgerald
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Smittenaar
authors.affiliation: MR Research in Neurology and Psychiatry, Goettingen University, Goettingen, Germany.
authors.forename: Gunther
authors.initials: G
authors.lastname: Helms
authors.affiliation: Department des Neurosciences Cliniques, LREN, CHUV, Universite de Lausanne, Lausanne, Switzerland.
authors.forename: Antoine
authors.initials: A
authors.lastname: Lutti
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, UK.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Weiskopf
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D019189:Iron Metabolism Disorders / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D019150:Neuroaxonal Dystrophies / Q000378:metabolism / Q000473:pathology; D059906:Neuroimaging / Q000379:methods*; D055815:Young Adult
chemical_list: D007501:Iron
keywords: 3T; Aging; MT; Magnetization transfer; Quantitative; R1; R2*; Relaxation; T1; T2*; VBQ; Water content