title: Apolipoprotein E and gray matter volume loss in patients with mild cognitive impairment and Alzheimer disease.
abstract: OBJECTIVE
  To examine the influence of apoliprotein E ε4 allele (APOE4) carrier status on disease progression by evaluating the rate of regional gray matter (GM) volume loss and disease severity in patients with newly diagnosed Alzheimer disease (AD) and stable amnestic mild cognitive impairment (MCI).
  
  
  METHODS
  This study was approved by the institutional review board and was HIPAA compliant. All subjects or their legal representatives gave informed consent for participation. Ninety-five subjects (63 male; average age, 77.1 years; age range, 58-91 years; 51 APOE4 carriers; 44 noncarriers) with either documented MCI to AD conversion or stable amnestic MCI underwent three yearly magnetic resonance imaging examinations. Voxel-based morphometry for image postprocessing and Clinical Dementia Rating (CDR) scale for cognitive assessment were used.
  
  
  RESULTS
  In APOE4 carriers, GM volume loss affected the hippocampi, temporal and parietal lobes, right caudate nucleus, and insulae in patients with MCI to AD conversion and the insular and temporal lobes in patients in whom MCI was stable. In subjects who were not APOE4 carriers, there was no significant GM volume change. There were no differences in CDR scores between APOE4 carriers and noncarriers.
  
  
  CONCLUSIONS
  APOE4 carriers with cognitive decline undergo faster GM atrophy than do noncarriers. The involvement of APOE4 in the progression of hippocampal atrophy, neocortical atrophy, or both has potential important implications for diagnosis and therapeutic approaches in patients with AD and should be considered in clinical trials. The present results and the results of prior studies indicate that the rate of hippocampal and neocortical atrophy is greater in association with APOE4 in nondemented elderly subjects, subjects with MCI, and those with AD.
authors.affiliation: Department of Radiology, Medical University of South Carolina, 96 Jonathan Lucas St, MSC 323, Charleston, SC, USA. spampin@musc.edu
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Spampinato
authors.forename: Zoran
authors.initials: Z
authors.lastname: Rumboldt
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hosker
authors.forename: Jacobo E
authors.initials: JE
authors.lastname: Mintzer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics*; D001284:Atrophy / Q000235:genetics / Q000473:pathology; D015415:Biomarkers; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers