title: Precuneus atrophy in early-onset Alzheimer's disease: a morphometric structural MRI study.
abstract: BACKGROUND
  Alzheimer's disease (AD) usually first presents in elderly patients, but may also develop at an earlier age. Patients with an early age at onset tend to present with complaints other than memory impairment, such as visuospatial problems or apraxia, which may reflect a different distribution of cortical involvement. In this study we set out to investigate whether age at onset in patients with AD determines the pattern of atrophy on cerebral MRI scans.
  
  
  METHODS
  We examined 55 patients with AD over a wide age range and analyzed their 3-D T1-weighted structural MRI scans in standard space using voxel-based morphometry (VBM). Regression analysis was performed to estimate loss of grey matter as a function of age, corrected for mini-mental state examination (MMSE) scores and sex.
  
  
  RESULTS
  The VBM analyses identified multiple areas (including the temporal and parietal lobes), showing more atrophy with advancing age. By contrast, a younger age at onset was found to be associated with lower grey matter density in the precuneus. Regionalized volumetric analysis of this region confirmed the existence of disproportionate atrophy in the precuneus in patients with early-onset AD. Application of a multivariate model with precuneus grey matter density as input, showed that precuneal and hippocampal atrophy are independent from each other. Additionally, we found that a smaller precuneus is associated with impaired visuospatial functioning.
  
  
  CONCLUSIONS
  Our findings support the notion that age at onset modulates the distribution of cortical involvement, and that disproportionate precuneus atrophy is more prominent in patients with a younger age of onset.
authors.affiliation: Department of Diagnostic Radiology, Vrije Universiteit Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. GB.Karas@vumc.nl
authors.forename: Giorgos
authors.initials: G
authors.lastname: Karas
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Serge
authors.initials: S
authors.lastname: Rombouts
authors.forename: Ronald
authors.initials: R
authors.lastname: van Schijndel
authors.forename: Martin
authors.initials: M
authors.lastname: Klein
authors.forename: Bethany
authors.initials: B
authors.lastname: Jones
authors.forename: Wiesje
authors.initials: W
authors.lastname: van der Flier
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged