title: Acceleration of cortical thinning in familial Alzheimer's disease.
abstract: BACKGROUND
  MRI in presymptomatic autosomal dominant Alzheimer's disease mutation carriers (MC) provides an opportunity to detect changes that pre-date symptoms or clinical diagnosis. We used automated cortical thickness (CTh) measurement to compare the grey matter of such a group with cognitively normal controls.
  
  
  METHODS
  9 presymptomatic mutation carriers (4 PSEN1, 5 APP) and 25 healthy, age and sex-matched controls underwent longitudinal volumetric MRI brain imaging. CTh measurement was performed across the whole brain using a validated, automated technique. Four regions of interest (ROI) (entorhinal cortex (ERC), parahippocampal gyrus (PHG), posterior cingulate cortex and precuneus) and two control regions (paracentral and pericalcarine) were selected on the basis of imaging data in existing Alzheimer's disease (AD) literature. Linear mixed models were used to describe normal ageing in controls and the extent to which mean CTh in cases differed from controls according to time since clinical diagnosis, adjusting for normal ageing.
  
  
  RESULTS
  An accelerating decline in CTh was observed across all ROI in the MC group. No such decline was demonstrated in the control regions for the MC group. Relative to controls, and adjusting for normal ageing, there was evidence (p=0.05, one-sided test) of lower CTh in the posterior cingulate up to 1.8 years prior to diagnosis and in the precuneus up to 4.1 years prior to diagnosis in the MC group.
  
  
  CONCLUSIONS
  Automated CTh analysis is a relatively practical, rapid and effective technique for assessing subtle structural change in AD. There is evidence that cortical thickness is reduced in mutation carriers a number of years prior to clinical diagnosis.
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK. knight@drc.ion.ucl.ac.uk
authors.forename: W D
authors.initials: WD
authors.lastname: Knight
authors.forename: L G
authors.initials: LG
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Douiri
authors.forename: C
authors.initials: C
authors.lastname: Frost
authors.forename: M N
authors.initials: MN
authors.lastname: Rossor
authors.forename: N C
authors.initials: NC
authors.lastname: Fox
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D005192:Family Health; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1