title: Imaging of onset and progression of Alzheimer's disease with voxel-compression mapping of serial magnetic resonance images.
abstract: BACKGROUND
  Early diagnosis and monitoring of the progression of Alzheimer's disease is important for the development of therapeutic strategies. To detect the earliest structural brain changes, individuals need to be studied before symptom onset. We used an imaging technique known as voxel-compression mapping to localise progressive atrophy in patients with preclinical Alzheimer's disease.
  
  
  METHODS
  Four symptom-free individuals from families with early-onset Alzheimer's disease with known autosomal dominant mutations underwent serial magnetic resonance imaging (MRI) over 5-8 years. All four became symptomatic during follow-up. 20 individuals with a clinical diagnosis of probable Alzheimer's disease and 20 control participants also underwent serial MR imaging. A non-linear fluid matching algorithm was applied to register repeat scans onto baseline imaging. Jacobian determinants were used to create the voxel-compression maps.
  
  
  RESULTS
  Progressive atrophy was revealed in presymptomatic individuals, with posterior cingulate and neocortical temporoparietal cortical losses, and medial temporal-lobe atrophy. In patients with known Alzheimer's disease, atrophy was widespread apart from in the primary motor and sensory cortices and cerebellum, reflecting the clinical phenomenology.
  
  
  CONCLUSIONS
  Voxel-compression maps confirmed early involvement of the medial temporal lobes, but also showed posterior cingulate and temporoparietal cortical losses at presymptomatic stage. This technique could be applied diagnostically and used to monitor the effects of therapeutic intervention.
authors.affiliation: Dementia Research Group, Department of Clinical Neurology, Institute of Neurology, University College London, London, UK. nfox@dementia.ion.ucl.ac.uk
authors.forename: N C
authors.initials: NC
authors.lastname: Fox
authors.forename: W R
authors.initials: WR
authors.lastname: Crum
authors.forename: R I
authors.initials: RI
authors.lastname: Scahill
authors.forename: J M
authors.initials: JM
authors.lastname: Stevens
authors.forename: J C
authors.initials: JC
authors.lastname: Janssen
authors.forename: M N
authors.initials: MN
authors.lastname: Rossor
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D013382:Subtraction Technique; D013997:Time Factors