title: Whole-brain atrophy rate in Alzheimer disease: identifying fast progressors.
abstract: OBJECTIVE
  To assess which baseline clinical and MRI measures influence whole-brain atrophy rates, measured from serial MR imaging.
  
  
  METHODS
  We recruited 65 patients with Alzheimer disease (mean +/- SD age 70 +/- 8 y, 58% women, Mini-Mental State Examination [MMSE] 22 +/- 5), scanned with an average interval of 1.7 +/- 0.6 years. Whole-brain atrophy rates were used as outcome measure. Baseline normalized brain volume, hippocampal volume, and whole-brain atrophy rates were measured using three-dimensional T1-weighted imaging. The influence of age, sex, apolipoprotein E genotype (APOE), baseline MMSE, baseline hippocampal volume, and baseline normalized brain volume on whole-brain atrophy rates was assessed using linear regression.
  
  
  RESULTS
  The mean whole-brain atrophy rate was -1.9 +/- 0.9% per year. In the multivariate model, younger age (beta [SE] = 0.03 [0.01]; p = 0.04), absence of APOE epsilon 4 (beta [SE] = 0.61 [0.28]; p = 0.03), and a low MMSE (beta [SE] = 0.11 [0.03]; p < 0.001) were associated with a higher whole-brain atrophy rate. Furthermore, a relatively spared hippocampus predicted faster decline for patients with a smaller baseline brain volume (p = 0.09), and with a lower MMSE (p = 0.07). Finally, a smaller brain volume was associated with a higher rate of atrophy in younger patients (p = 0.03).
  
  
  CONCLUSIONS
  Our results suggest it is possible to characterize a subgroup of patients with Alzheimer disease (AD) who are at risk of faster loss of brain volume. Patients with more generalized, rather than focal hippocampal atrophy, who often have an onset before the age of 65, and are APOE epsilon 4 negative, seem to be at risk of faster whole-brain atrophy rates than the more commonly seen patients with AD, who are older, are APOE epsilon 4 positive, and have pronounced hippocampal atrophy.
authors.affiliation: Department of Radiology and Alzheimer Centre, Vrije Universiteit Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands. jd.sluimer@vumc.nl
authors.forename: J D
authors.initials: JD
authors.lastname: Sluimer
authors.forename: H
authors.initials: H
authors.lastname: Vrenken
authors.forename: M A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: N C
authors.initials: NC
authors.lastname: Fox
authors.forename: P
authors.initials: P
authors.lastname: Scheltens
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: W M
authors.initials: WM
authors.lastname: van der Flier
mesh_terms: D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D001284:Atrophy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D015984:Causality; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011379:Prognosis; D017678:Sex Distribution; D013997:Time Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E