title: Age independently affects myelin integrity as detected by magnetization transfer magnetic resonance imaging in multiple sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) is a heterogeneous disorder with a progressive course that is difficult to predict on a case-by-case basis. Natural history studies of MS have demonstrated that age influences clinical progression independent of disease duration.
  
  
  OBJECTIVE
  To determine whether age would be associated with greater CNS injury as detected by magnetization transfer MRI.
  
  
  METHODS
  Forty MS patients were recruited from out-patient clinics into two groups stratified by age but with similar clinical disease duration as well as thirteen controls age-matched to the older MS group. Images were segmented by automated programs and blinded readers into normal appearing white matter (NAWM), normal appearing gray matter (NAGM), and white matter lesions (WMLs) and gray matter lesions (GMLs) in the MS groups. WML and GML were delineated on T2-weighted 3D fluid-attenuated inversion recovery (FLAIR) and T1 weighted MRI volumes. Mean magnetization transfer ratio (MTR), region volume, as well as MTR histogram skew and kurtosis were calculated for each region.
  
  
  RESULTS
  All MTR measures in NAGM and MTR histogram metrics in NAWM differed between MS subjects and controls, as expected and previously reported by several studies, but not between MS groups. However, MTR measures in the WML did significantly differ between the MS groups, in spite of no significant differences in lesion counts and volumes.
  
  
  CONCLUSIONS
  Despite matching for clinical disease duration and recording no significant WML volume difference, we demonstrated strong MTR differences in WMLs between younger and older MS patients. These data suggest that aging-related processes modify the tissue response to inflammatory injury and its clinical outcome correlates in MS.
authors.affiliation: Imanova Centre for Imaging Sciences, London, UK ; Division of Experimental Medicine, Imperial College London, UK.
authors.forename: R D
authors.initials: RD
authors.lastname: Newbould
authors.affiliation: Division of Brain Sciences, Imperial College London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Nicholas
authors.affiliation: Division of Brain Sciences, Imperial College London, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Thomas
authors.affiliation: Department of Imaging, Imperial College Healthcare NHS Trust, UK.
authors.forename: R
authors.initials: R
authors.lastname: Quest
authors.affiliation: Division of Brain Sciences, Imperial College London, UK.
authors.forename: J S Z
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Imaging, Imperial College Healthcare NHS Trust, UK.
authors.forename: L
authors.initials: L
authors.lastname: Honeyfield
authors.affiliation: Imanova Centre for Imaging Sciences, London, UK ; Division of Brain Sciences, Imperial College London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Colasanti
authors.affiliation: Division of Brain Sciences, Imperial College London, UK.
authors.forename: O
authors.initials: O
authors.lastname: Malik
authors.affiliation: Division of Brain Sciences, Imperial College London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Mattoscio
authors.affiliation: Division of Brain Sciences, Imperial College London, UK ; Neurosciences, GlaxoSmithKline Research and Development, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: Matthews
authors.affiliation: Department of Health Sciences (DISSAL), University of Genoa, Italy.
authors.forename: M P
authors.initials: MP
authors.lastname: Sormani
authors.affiliation: Division of Brain Sciences, Imperial College London, UK ; Department of Imaging, Imperial College Healthcare NHS Trust, UK.
authors.forename: A D
authors.initials: AD
authors.lastname: Waldman
authors.affiliation: Division of Brain Sciences, Imperial College London, UK ; Department of Clinical Neurosciences, Imperial College Healthcare NHS Trust, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Muraro
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology*; D012372:ROC Curve
keywords: Aging; GM, gray matter; GML, gray matter lesion; MRI; MTR, magnetization transfer ratio; Magnetization transfer; Multiple sclerosis; NAGM, normal appearing gray matter; NAWM, normal appearing white matter; WM, white matter; WML, white matter lesion