title: White Matter Degeneration with Aging: Longitudinal Diffusion MR Imaging Analysis.
abstract: OBJECTIVE
  To determine longitudinally the rate of change in diffusion-tensor imaging (DTI) parameters of white matter microstructure with aging and to investigate whether cardiovascular risk factors influence this longitudinal change.
  
  
  METHODS
  This prospective population-based cohort study was approved by a dedicated ethics committee overseen by the national government, and all participants gave written informed consent. Community-dwelling participants without dementia were examined by using a research-dedicated 1.5-T magnetic resonance (MR) imager on two separate visits that were, on average, 2.0 years apart. Among 810 persons who were eligible for imaging at baseline, longitudinal imaging data were available for 501 persons (mean age, 69.9 years; age range, 64.1-91.1 years). Changes in normal-appearing white matter DTI characteristics in the tract centers were analyzed globally to investigate diffuse patterns of change and then locally by using voxelwise multilinear regression. The influence of cardiovascular risk factors was assessed by treating them as additional determinants in both analyses.
  
  
  RESULTS
  Over the 2.0-year follow-up interval, global fractional anisotropy (FA) decreased by 0.0042 (P < .001), while mean diffusivity (MD) increased by 8.1 × 10(-6) mm(2)/sec (P < .001). Voxelwise analysis of the brain white matter skeleton showed an average decrease of 0.0082 (Pmean = .002) in FA in 57% of skeleton voxels. The sensorimotor pathway, however, showed an increase of 0.0078 (Pmean = .009) in FA. MD increased by 10.8 × 10(-6)mm(2)/sec (Pmean < .001) on average in 79% of white matter skeleton voxels. Additionally, white matter degeneration was more pronounced in older persons. Cardiovascular risk factors were generally not associated with longitudinal changes in white matter microstructure.
  
  
  CONCLUSIONS
  Longitudinal diffusion analysis indicates widespread microstructural deterioration of the normal-appearing white matter in normal aging, with relative sparing of sensorimotor fibers.
authors.affiliation: From the Departments of Radiology (M.d.G., L.G.M.C., M.A.I., G.P.K., A.v.d.L., W.J.N., M.W.V.), Medical Informatics (M.d.G., W.J.N.), Epidemiology (M.d.G., L.G.M.C., M.A.I., A.H., M.W.V.), and Neurology (M.A.I.), Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Room Ca220, 3000 CA Rotterdam, the Netherlands; and Department of Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands (W.J.N.).
authors.forename: Marius
authors.initials: M
authors.lastname: de Groot
authors.affiliation: From the Departments of Radiology (M.d.G., L.G.M.C., M.A.I., G.P.K., A.v.d.L., W.J.N., M.W.V.), Medical Informatics (M.d.G., W.J.N.), Epidemiology (M.d.G., L.G.M.C., M.A.I., A.H., M.W.V.), and Neurology (M.A.I.), Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Room Ca220, 3000 CA Rotterdam, the Netherlands; and Department of Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands (W.J.N.).
authors.forename: Lotte G M
authors.initials: LG
authors.lastname: Cremers
authors.affiliation: From the Departments of Radiology (M.d.G., L.G.M.C., M.A.I., G.P.K., A.v.d.L., W.J.N., M.W.V.), Medical Informatics (M.d.G., W.J.N.), Epidemiology (M.d.G., L.G.M.C., M.A.I., A.H., M.W.V.), and Neurology (M.A.I.), Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Room Ca220, 3000 CA Rotterdam, the Netherlands; and Department of Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands (W.J.N.).
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: From the Departments of Radiology (M.d.G., L.G.M.C., M.A.I., G.P.K., A.v.d.L., W.J.N., M.W.V.), Medical Informatics (M.d.G., W.J.N.), Epidemiology (M.d.G., L.G.M.C., M.A.I., A.H., M.W.V.), and Neurology (M.A.I.), Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Room Ca220, 3000 CA Rotterdam, the Netherlands; and Department of Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands (W.J.N.).
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: From the Departments of Radiology (M.d.G., L.G.M.C., M.A.I., G.P.K., A.v.d.L., W.J.N., M.W.V.), Medical Informatics (M.d.G., W.J.N.), Epidemiology (M.d.G., L.G.M.C., M.A.I., A.H., M.W.V.), and Neurology (M.A.I.), Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Room Ca220, 3000 CA Rotterdam, the Netherlands; and Department of Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands (W.J.N.).
authors.forename: Gabriel P
authors.initials: GP
authors.lastname: Krestin
authors.affiliation: From the Departments of Radiology (M.d.G., L.G.M.C., M.A.I., G.P.K., A.v.d.L., W.J.N., M.W.V.), Medical Informatics (M.d.G., W.J.N.), Epidemiology (M.d.G., L.G.M.C., M.A.I., A.H., M.W.V.), and Neurology (M.A.I.), Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Room Ca220, 3000 CA Rotterdam, the Netherlands; and Department of Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands (W.J.N.).
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.affiliation: From the Departments of Radiology (M.d.G., L.G.M.C., M.A.I., G.P.K., A.v.d.L., W.J.N., M.W.V.), Medical Informatics (M.d.G., W.J.N.), Epidemiology (M.d.G., L.G.M.C., M.A.I., A.H., M.W.V.), and Neurology (M.A.I.), Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Room Ca220, 3000 CA Rotterdam, the Netherlands; and Department of Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands (W.J.N.).
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.affiliation: From the Departments of Radiology (M.d.G., L.G.M.C., M.A.I., G.P.K., A.v.d.L., W.J.N., M.W.V.), Medical Informatics (M.d.G., W.J.N.), Epidemiology (M.d.G., L.G.M.C., M.A.I., A.H., M.W.V.), and Neurology (M.A.I.), Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Room Ca220, 3000 CA Rotterdam, the Netherlands; and Department of Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands (W.J.N.).
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
mesh_terms: D000368:Aged; D016880:Anisotropy; D002318:Cardiovascular Diseases / Q000150:complications; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009426:Netherlands; D011446:Prospective Studies; D012307:Risk Factors