White matter hyperintensities are more highly associated with preclinical Alzheimer's disease than imaging and cognitive markers of neurodegeneration

Benjamin M. Kandel, Brian B. Avants, James C. Gee, Corey T. McMillan, Guray Erus, Jimit Doshi, Christos Davatzikos, David A. Wolk

Research output: Contribution to journalArticle


Introduction: 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. Discussion: WMH volume is more highly associated with preclinical AD than other AD biomarkers.

Original languageEnglish (US)
Pages (from-to)18-27
Number of pages10
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Publication statusPublished - 2016
Externally publishedYes



  • Aging
  • Alzheimer's disease
  • Amyloid
  • Leukoaraiosis
  • MRI
  • PET
  • Preclinical Alzheimer's disease
  • White matter

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Neurology

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