White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy

Cassidy M Fiford, Emily N Manning, Jonathan W Bartlett, David M Cash, Ian B Malone, Gerard R Ridgway, Manja Lehmann, Kelvin K Leung, Carole H Sudre, Sebastien Ourselin, Geert Jan Biessels, Owen T Carmichael, Nick C Fox, M Jorge Cardoso, Josephine Barnes

Research output: Contribution to journalArticlepeer-review

58 Citations (SciVal)


This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5-T MRI. CSF Aβ42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)249-262
Number of pages14
Issue number3
Early online date9 Dec 2016
Publication statusPublished - Mar 2017


  • Aged
  • Aging
  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Atrophy
  • Biomarkers
  • Cognitive Dysfunction
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Hippocampus
  • Humans
  • Image Processing, Computer-Assisted
  • Linear Models
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Organ Size
  • Peptide Fragments
  • White Matter
  • Journal Article


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