title: The dynamics of cortical and hippocampal atrophy in Alzheimer disease.
abstract: OBJECTIVE
  To characterize rates of regional Alzheimer disease (AD)-specific brain atrophy across the presymptomatic, mild cognitive impairment, and dementia stages.
  
  
  METHODS
  Multicenter case-control study of neuroimaging, cerebrospinal fluid, and cognitive test score data from the Alzheimer's Disease Neuroimaging Initiative.
  
  
  METHODS
  Research centers across the United States and Canada.
  
  
  METHODS
  We examined a total of 317 participants with baseline cerebrospinal fluid biomarker measurements and 3 T1-weighted magnetic resonance images obtained within 1 year.
  
  
  METHODS
  We used automated tools to compute annual longitudinal atrophy in the hippocampus and cortical regions targeted in AD. We used Mini-Mental State Examination scores as a measure of cognitive performance. We performed a cross-subject analysis of atrophy rates and acceleration on individuals with an AD-like cerebrospinal fluid molecular profile.
  
  
  RESULTS
  In presymptomatic individuals harboring indicators of AD, baseline thickness in AD-vulnerable cortical regions was significantly reduced compared with that of healthy control individuals, but baseline hippocampal volume was not. Across the clinical spectrum, rates of AD-specific cortical thinning increased with decreasing cognitive performance before peaking at approximately the Mini-Mental State Examination score of 21, beyond which rates of thinning started to decline. Annual rates of hippocampal volume loss showed a continuously increasing pattern with decreasing cognitive performance as low as the Mini-Mental State Examination score of 15. Analysis of the second derivative of imaging measurements revealed that AD-specific cortical thinning exhibited early acceleration followed by deceleration. Conversely, hippocampal volume loss exhibited positive acceleration across all study participants.
  
  
  CONCLUSIONS
  Alzheimer disease-specific cortical thinning and hippocampal volume loss are consistent with a sigmoidal pattern, with an acceleration phase during the early stages of the disease. Clinical trials should carefully consider the nonlinear behavior of these AD biomarkers.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, 02129, USA. msabuncu@csail.mit.edu
authors.forename: Mert R
authors.initials: MR
authors.lastname: Sabuncu
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Desikan
authors.forename: Jorge
authors.initials: J
authors.lastname: Sepulcre
authors.forename: Boon Thye T
authors.initials: BT
authors.lastname: Yeo
authors.forename: Hesheng
authors.initials: H
authors.lastname: Liu
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schmansky
authors.forename: Martin
authors.initials: M
authors.lastname: Reuter
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: Randy L
authors.initials: RL
authors.lastname: Buckner
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.forename: Bruce
authors.initials: B
authors.lastname: Fischl
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001284:Atrophy; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology*