title: Apolipoprotein E-dependent load of white matter hyperintensities in Alzheimer's disease: a voxel-based lesion mapping study.
abstract: BACKGROUND
  White matter (WM) magnetic resonance imaging (MRI) hyperintensities are common in Alzheimer's disease (AD), but their pathophysiological relevance and relationship to genetic factors are unclear. In the present study, we investigated potential apolipoprotein E (APOE)-dependent effects on the extent and cognitive impact of WM hyperintensities in patients with AD.
  
  
  METHODS
  WM hyperintensity volume on fluid-attenuated inversion recovery images of 201 patients with AD (128 carriers and 73 non-carriers of the APOE ε4 risk allele) was determined globally as well as regionally with voxel-based lesion mapping. Clinical, neuropsychological and MRI data were collected from prospective multicenter trials conducted by the German Dementia Competence Network.
  
  
  RESULTS
  WM hyperintensity volume was significantly greater in non-carriers of the APOE ε4 allele. Lesion distribution was similar among ε4 carriers and non-carriers. Only ε4 non-carriers showed a correlation between lesion volume and cognitive performance.
  
  
  CONCLUSIONS
  The current findings indicate an increased prevalence of WM hyperintensities in non-carriers compared with carriers of the APOE ε4 allele among patients with AD. This is consistent with a possibly more pronounced contribution of heterogeneous vascular risk factors to WM damage and cognitive impairment in patients with AD without APOE ε4-mediated risk.
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, 68159, Mannheim, Germany ; AHG-Klinik für Psychosomatik, Kurbrunnenstr. 12, 67098, Bad Dürkheim, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Morgen
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, 68159, Mannheim, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, 68159, Mannheim, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Frölich
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, 68159, Mannheim, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Tost
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, 68159, Mannheim, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Plichta
authors.affiliation: Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Kölsch
authors.affiliation: Department of Medical Informatics, University of Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Rakebrandt
authors.affiliation: Department of Medical Informatics, University of Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
authors.forename: Otto
authors.initials: O
authors.lastname: Rienhoff
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Holbeinstr. 13-15, 53175, Bonn, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Peters
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Hamburg, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Jahn
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Düsseldorf, Bergische Landstr. 2, 40629, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Luckhaus
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg, Hauptstr. 5 79104, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hüll
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Leipzig, Semmelweisstr. 10, 04103, Leipzig, Germany.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gertz
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Heidelberg, Voßstr. 5, 69115, Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schröder
authors.affiliation: Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer, Hôpital de la Salpêtrière Paris, Université Pierre et Marie Curie, 47 Blvd. de lHopital, 75013, Paris, France.
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Rostock and DZNE Rostock, Gehlsheimerstr. 20, 18147 Rostock, Rostock, Germany.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.affiliation: Institute of General Practice, University of Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Pantel
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Heuser
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Essen, Virchowstr. 174, 45147, Essen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Göttingen, Von-Siebold-Str. 5, 37075, Göttingen, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Rüther
authors.affiliation: Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Holbeinstr. 13-15, 53175, Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, 68159, Mannheim, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg