title: APOE ε4 is associated with disproportionate progressive hippocampal atrophy in AD.
abstract: OBJECTIVE
  To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates.
  
  
  METHODS
  MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. MCI subjects were divided into "progressors" (MCI-P) if diagnosed with AD within 36 months or "stable" (MCI-S) if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated.
  
  
  RESULTS
  Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests) compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P.
  
  
  CONCLUSIONS
  These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD.
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Emily N
authors.initials: EN
authors.lastname: Manning
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Josephine
authors.initials: J
authors.lastname: Barnes
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom; Centre for Medical Image Computing, University College London, London, United Kingdom.
authors.forename: David M
authors.initials: DM
authors.lastname: Cash
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Bartlett
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom; Centre for Medical Image Computing, University College London, London, United Kingdom.
authors.forename: Kelvin K
authors.initials: KK
authors.lastname: Leung
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom; Centre for Medical Image Computing, University College London, London, United Kingdom.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ourselin
authors.forename: Nick C
authors.initials: NC
authors.lastname: Fox
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001284:Atrophy / Q000235:genetics; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000235:genetics / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male
chemical_list: D053327:Apolipoprotein E4