title: APOE ε4 and risk for Alzheimer's disease: do regionally distributed white matter hyperintensities play a role?
abstract: BACKGROUND
  We previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase the risk for Alzheimer's disease (AD). Here, we examined whether individuals with apolipoprotein E gene (APOE ε4) have increased parietal WMH volume.
  
  
  METHODS
  Participants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n = 694, 47 with dementia) in northern Manhattan and the Etude Santé Psychologique Prévalence Risques et Traitement study (ESPRIT; n = 539, 8 with dementia) in Montpellier. The association between regional WMH and APOE ε4 was examined separately in each group and then in a combined analysis.
  
  
  RESULTS
  In WHICAP, ε4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, ε4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, ε4 carriers had higher WMH in parietal and occipital lobes. Increased WMH volume was associated with increased frequency of dementia irrespective of APOE ε4 status; those with the ε4 were more likely to have dementia if they also had increased parietal WMH.
  
  
  CONCLUSIONS
  APOE ε4 is associated with increased parietal lobe WMH.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: amb2139@columbia.edu.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brickman
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupf
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Manly
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Stern
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: José A
authors.initials: JA
authors.lastname: Luchsinger
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Provenzano
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Atul
authors.initials: A
authors.lastname: Narkhede
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Qolamreza
authors.initials: Q
authors.lastname: Razlighi
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Lyndsey
authors.initials: L
authors.lastname: Collins-Praino
authors.affiliation: Inserm, 1061 Neuropsychiatry, La Colombière Hospital, Montpellier, France; Faculty of Medicine University of Montpellier 1, Montpellier, France.
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Artero
authors.affiliation: Inserm, 1061 Neuropsychiatry, La Colombière Hospital, Montpellier, France; Faculty of Medicine University of Montpellier 1, Montpellier, France; Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College, University College London, London, UK.
authors.forename: Tasnime N
authors.initials: TN
authors.lastname: Akbaraly
authors.affiliation: Inserm, 1061 Neuropsychiatry, La Colombière Hospital, Montpellier, France; Faculty of Medicine University of Montpellier 1, Montpellier, France; Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College, University College London, London, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Ritchie
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: rpm2@cumc.columbia.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
authors.affiliation: Inserm, 1061 Neuropsychiatry, La Colombière Hospital, Montpellier, France; Faculty of Medicine University of Montpellier 1, Montpellier, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Portet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000473:pathology*; D012189:Retrospective Studies; D066127:White Matter / Q000473:pathology*
chemical_list: D053327:Apolipoprotein E4
keywords: APOE; Alzheimer's disease; White matter hyperintensities