title: White matter damage in Alzheimer disease and its relationship to gray matter atrophy.
abstract: OBJECTIVE
  To explore the regional patterns of white matter (WM) tract damage in (a) patients with probable Alzheimer disease (AD) and (b) patients with amnestic mild cognitive impairment (aMCI) and at least one abnormal biomarker and to investigate whether WM damage is related to gray matter (GM) atrophy.
  
  
  METHODS
  This study was approved by the institutional review board, and written informed consent was obtained from each participant. Twenty-three patients with AD, 15 patients with aMCI, and 15 healthy control subjects underwent diffusion tensor magnetic resonance imaging. WM tract damage was investigated by using tract-based spatial statistics, and GM atrophy was measured by using voxel-based morphometry.
  
  
  RESULTS
  Compared with control subjects, patients with AD had an increase in mean diffusivity in all major WM tracts studied, including the limbic, cortico-cortical, interhemispheric, and corticospinal tracts. Conversely, fractional anisotropy decreased only in the parahippocampal tract, fornix, and small, inferior parietal regions. In addition, patients with AD showed a widespread increase in axial and radial diffusivity compared with control subjects. Patients with aMCI showed an increase in axial diffusivity only in tracts projecting to the frontal cortex and splenium of the corpus callosum. Significant and anatomically congruent correlations between WM changes and regional GM atrophy were found in patients with AD. Conversely, damage to most WM tracts in patients with aMCI did not correlate with GM atrophy.
  
  
  CONCLUSIONS
  In AD, the observed patterns of WM abnormalities may reflect the advanced phase of a secondary degenerative process and an association, especially in the early phases of the disease, with primary WM tract damage over and above GM abnormalities.
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.forename: Michela
authors.initials: M
authors.lastname: Pievani
authors.forename: Stefania
authors.initials: S
authors.lastname: Sala
authors.forename: Cristina
authors.initials: C
authors.lastname: Geroldi
authors.forename: Samantha
authors.initials: S
authors.lastname: Galluzzi
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology* / Q000523:psychology; D001284:Atrophy / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000473:pathology / Q000523:psychology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009483:Neuropsychological Tests; D011446:Prospective Studies; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers