title: White matter atrophy in Alzheimer's disease variants.
abstract: BACKGROUND
  In comparison with late-onset Alzheimer's disease (LOAD, onset, >65 years), early-age-of-onset Alzheimer's disease (EOAD, onset, <65 years) more often presents with language, visuospatial, and/or executive impairment, often occurring earlier than a progressive memory deficit. The logopenic variant of primary progressive aphasia (lv-PPA) and posterior cortical atrophy (PCA) have recently been described as possible atypical variants of EOAD. Lv-PPA is characterized by isolated language deficit, whereas PCA is characterized by predominant visuospatial deficits. Severe hemispheric gray matter (GM) atrophy associated with EOAD, lv-PPA, and PCA has been described, but regional patterns of white matter (WM) damage are still poorly understood.
  
  
  METHODS
  Using structural magnetic resonance imaging and voxel-based morphometry, we investigated WM damage in patients with EOAD (n = 16), PCA (n = 13), lv-PPA (n = 10), and LOAD (n = 14) at presentation and 72 age-matched control subjects.
  
  
  RESULTS
  In patients with EOAD, PCA, and lv-PPA, WM atrophy was centered on the lateral temporal and parietal regions, including the cingulum and posterior corpus callosum. Compared with control subjects, patients with lv-PPA showed more severe left parietal damage, and patients with PCA showed more severe occipital atrophy. Moreover, patients with EOAD had greater cingulum atrophy compared with those with LOAD. LOAD showed WM damage in the medial temporal regions and less extensive hemispheric involvement.
  
  
  CONCLUSIONS
  Patterns of WM damage in EOAD, lv-PPA, and PCA are consistent with the clinical syndromes and GM atrophy patterns. WM injury in AD atypical variants may contribute to symptoms and disease pathogenesis.
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Migliaccio
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Possin
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Gorno-Tempini
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*