title: Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI.
abstract: OBJECTIVE
  To test the hypothesis that the atrophy rate measured from serial MRI studies is associated with time to subsequent clinical conversion to a more impaired state in both cognitively healthy elderly subjects and in subjects with amnestic mild cognitive impairment (MCI).
  
  
  METHODS
  Ninety-one healthy elderly patients and 72 patients with amnestic MCI who met inclusion criteria were identified from the Mayo Alzheimer's Disease Research Center and Alzheimer's Disease Patient Registry. Atrophy rates of four different brain structures--hippocampus, entorhinal cortex, whole brain, and ventricle--were measured from a pair of MRI studies separated by 1 to 2 years. The time of the second scan marked the beginning of the clinical observation period.
  
  
  RESULTS
  During follow-up, 13 healthy patients converted to MCI or Alzheimer disease (AD), whereas 39 MCI subjects converted to AD. Among those healthy at baseline, only larger ventricular annual percent volume change (APC) was associated with a higher risk of conversion (hazard ratio for a 1-SD increase 1.9, p = 0.03). Among MCI subjects, both greater ventricular volume APC (hazard ratio for a 1-SD increase 1.7, p < 0.001) and greater whole brain APC (hazard ratio for a 1-SD increase 1.4, p = 0.007) increased the risk of conversion to AD. Both ventricular APC (hazard ratio for a 1-SD increase 1.59, p = 0.001) and whole brain APC (hazard ratio for a 1-SD increase 1.32, p = 0.009) provided additional predictive information to covariate-adjusted cross-sectional hippocampal volume at baseline about the risk of converting from MCI to AD.
  
  
  CONCLUSIONS
  Higher whole brain and ventricle atrophy rates 1 to 2 years before baseline are associated with an increased hazard of conversion to a more impaired state. Combining a measure of hippocampal volume at baseline with a measure of either whole brain or ventricle atrophy rates from serial MRI scans provides complimentary predictive information about the hazard of subsequent conversion from mild cognitive impairment to Alzheimer disease. However, overlap among those who did vs those who did not convert indicate that these measures are unlikely to provide absolute prognostic information for individual patients.
authors.affiliation: Department of Diagnostic Radiology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. jack.clifford@mayo.edu
authors.forename: C R
authors.initials: CR
authors.lastname: Jack
authors.forename: M M
authors.initials: MM
authors.lastname: Shiung
authors.forename: S D
authors.initials: SD
authors.lastname: Weigand
authors.forename: P C
authors.initials: PC
authors.lastname: O'Brien
authors.forename: J L
authors.initials: JL
authors.lastname: Gunter
authors.forename: B F
authors.initials: BF
authors.lastname: Boeve
authors.forename: D S
authors.initials: DS
authors.lastname: Knopman
authors.forename: G E
authors.initials: GE
authors.lastname: Smith
authors.forename: R J
authors.initials: RJ
authors.lastname: Ivnik
authors.forename: E G
authors.initials: EG
authors.lastname: Tangalos
authors.forename: R C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000367:Age Factors; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000647:Amnesia / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D001284:Atrophy / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D015331:Cohort Studies; D018450:Disease Progression; D018728:Entorhinal Cortex / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D011237:Predictive Value of Tests; D013997:Time Factors