title: Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration.
abstract: OBJECTIVE
  To quantify the regional and global cerebral atrophy rates and assess acceleration rates in healthy controls, subjects with mild cognitive impairment (MCI), and subjects with mild Alzheimer disease (AD).
  
  
  METHODS
  Using 0-, 6-, 12-, 18-, 24-, and 36-month MRI scans of controls and subjects with MCI and AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we calculated volume change of whole brain, hippocampus, and ventricles between all pairs of scans using the boundary shift integral.
  
  
  RESULTS
  We found no evidence of acceleration in whole-brain atrophy rates in any group. There was evidence that hippocampal atrophy rates in MCI subjects accelerate by 0.22%/year2 on average (p = 0.037). There was evidence of acceleration in rates of ventricular enlargement in subjects with MCI (p = 0.001) and AD (p < 0.001), with rates estimated to increase by 0.27 mL/year2 (95% confidence interval 0.12, 0.43) and 0.88 mL/year2 (95% confidence interval 0.47, 1.29), respectively. A post hoc analysis suggested that the acceleration of hippocampal loss in MCI subjects was mainly driven by the MCI subjects that were observed to progress to clinical AD within 3 years of baseline, with this group showing hippocampal atrophy rate acceleration of 0.50%/year2 (p = 0.003).
  
  
  CONCLUSIONS
  The small acceleration rates suggest a long period of transition to the pathologic losses seen in clinical AD. The acceleration in hippocampal atrophy rates in MCI subjects in the ADNI seems to be driven by those MCI subjects who concurrently progressed to a clinical diagnosis of AD.
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Kelvin K
authors.initials: KK
authors.lastname: Leung
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Bartlett
authors.forename: Josephine
authors.initials: J
authors.lastname: Barnes
authors.forename: Emily N
authors.initials: EN
authors.lastname: Manning
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ourselin
authors.forename: Nick C
authors.initials: NC
authors.lastname: Fox
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000235:genetics; D001284:Atrophy / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000473:pathology* / Q000503:physiopathology*; D016208:Databases, Factual / Q000706:statistics & numerical data; D018450:Disease Progression; D005260:Female; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E