title: White matter hyperintensities are more highly associated with preclinical Alzheimer's disease than imaging and cognitive markers of neurodegeneration.
abstract: BACKGROUND
  Cognitive tests and nonamyloid imaging biomarkers do not consistently identify preclinical AD. The objective of this study was to evaluate whether white matter hyperintensity (WMH) volume, a cerebrovascular disease marker, is more associated with preclinical AD than conventional AD biomarkers and cognitive tests.
  
  
  METHODS
  Elderly controls enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 158) underwent florbetapir-PET scans, psychometric testing, neuroimaging with MRI and PET, and APOE genetic testing. Elderly controls the Parkinson's progression markers initiative (PPMI, n = 58) had WMH volume, cerebrospinal fluid (CSF) Aβ1-42, and APOE status measured.
  
  
  RESULTS
  In the ADNI cohort, only WMH volume and APOE ε4 status were associated with cerebral Aβ (standardized β = 0.44 and 1.25, P = .03 and .002). The association between WMH volume and APOE ε4 status with cerebral Aβ (standardized β = 1.12 and 0.26, P = .048 and .045) was confirmed in the PPMI cohort.
  
  
  CONCLUSIONS
  WMH volume is more highly associated with preclinical AD than other AD biomarkers.
authors.affiliation: Penn Image Computing and Science Laboratory and Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Kandel
authors.affiliation: Penn Image Computing and Science Laboratory and Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Avants
authors.affiliation: Penn Image Computing and Science Laboratory and Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Gee
authors.affiliation: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Corey T
authors.initials: CT
authors.lastname: McMillan
authors.affiliation: Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA.
authors.forename: Guray
authors.initials: G
authors.lastname: Erus
authors.affiliation: Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA.
authors.forename: Jimit
authors.initials: J
authors.lastname: Doshi
authors.affiliation: Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA.
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.affiliation: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wolk
keywords: Aging; Alzheimer's disease; Amyloid; Leukoaraiosis; MRI; PET; Preclinical Alzheimer's disease; White matter