title: Widespread white matter degeneration preceding the onset of dementia.
abstract: BACKGROUND
  Brain atrophy in subjects with mild cognitive impairment (MCI) introduces partial volume effects, limiting the sensitivity of diffusion tensor imaging to white matter microstructural degeneration. Appropriate correction isolates microstructural effects in MCI that might be precursors of Alzheimer's disease (AD).
  
  
  METHODS
  Forty-eight participants (18 MCI, 15 AD, and 15 healthy controls) had magnetic resonance imaging scans and clinical evaluations at baseline and follow-up after 36 months. Ten MCI subjects were diagnosed with AD at follow-up and eight remained MCI. Free-water (FW) corrected measures on the white matter skeleton were compared between groups.
  
  
  RESULTS
  FW corrected radial diffusivity, but not uncorrected radial diffusivity, was increased across the brain of the converted group compared with the nonconverted group (P < .05). The extent of increases was similar to that found comparing AD with controls.
  
  
  CONCLUSIONS
  Partial volume elimination reveals microstructural alterations preceding dementia. These alterations may prove to be an effective and feasible early biomarker of AD.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Junior Group Medical Image Computing, German Cancer Research Center, Heidelberg, Germany; Junior Group Quantitative Image-based Disease Characterization, German Cancer Research Center, Heidelberg, Germany. Electronic address: k.maier-hein@dkfz.de.
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Maier-Hein
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Westin
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Health Scientist, Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, MA, USA.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Shenton
authors.affiliation: Center for Imaging of Neurodegenerative Disease, San Francisco VA Medical Center, University of California, San Francisco, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Image Data Evaluation and Analytics Lab (IDEAL), Weill Cornell Medical College, New York, NY, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Raj
authors.affiliation: Department of General Psychiatry, Section of Geriatric Psychiatry, Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Thomann
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Kikinis
authors.affiliation: Junior Group Quantitative Image-based Disease Characterization, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Bram
authors.initials: B
authors.lastname: Stieltjes
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ofer
authors.initials: O
authors.lastname: Pasternak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D060825:Cognitive Dysfunction / Q000150:complications; D003704:Dementia / Q000209:etiology*; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009410:Nerve Degeneration / Q000150:complications* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology*
keywords: Alzheimer's disease; Diffusion tensor imaging; Free-water imaging; Mild cognitive impairment; Partial volume elimination