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, for the Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)249-262
Number of pages14
JournalHippocampus
Volume27
Issue number3
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

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Atrophy
Cerebrospinal Fluid
Brain
Alzheimer Disease
Linear Models
Pathology
White Matter
Blood Vessels
Biomarkers

Keywords

  • Alzheimer's disease
  • hippocampus
  • mild cognitive impairment
  • vascular disease
  • white matter disease
  • white matter hyperintensity (WMH)

ASJC Scopus subject areas

  • Cognitive Neuroscience

Cite this

Fiford, C. M., Manning, E. N., Bartlett, J. W., Cash, D. M., Malone, I. B., Ridgway, G. R., ... for the Alzheimer's Disease Neuroimaging Initiative (2017). White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy. Hippocampus, 27(3), 249-262. https://doi.org/10.1002/hipo.22690

White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy. / Fiford, Cassidy M.; Manning, Emily N.; Bartlett, Jonathan W.; Cash, David M.; Malone, Ian B.; Ridgway, Gerard R.; Lehmann, Manja; Leung, Kelvin K.; Sudre, Carole H.; Ourselin, Sebastien; Biessels, Geert Jan; Carmichael, Owen T.; Fox, Nick C.; Cardoso, M. Jorge; Barnes, Josephine; for the Alzheimer's Disease Neuroimaging Initiative.

In: Hippocampus, Vol. 27, No. 3, 01.03.2017, p. 249-262.

Research output: Contribution to journalArticle

Fiford, CM, Manning, EN, Bartlett, JW, Cash, DM, Malone, IB, Ridgway, GR, Lehmann, M, Leung, KK, Sudre, CH, Ourselin, S, Biessels, GJ, Carmichael, OT, Fox, NC, Cardoso, MJ, Barnes, J & for the Alzheimer's Disease Neuroimaging Initiative 2017, 'White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy', Hippocampus, vol. 27, no. 3, pp. 249-262. https://doi.org/10.1002/hipo.22690
Fiford CM, Manning EN, Bartlett JW, Cash DM, Malone IB, Ridgway GR et al. White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy. Hippocampus. 2017 Mar 1;27(3):249-262. https://doi.org/10.1002/hipo.22690
Fiford, Cassidy M. ; Manning, Emily N. ; Bartlett, Jonathan W. ; Cash, David M. ; Malone, Ian B. ; Ridgway, Gerard R. ; Lehmann, Manja ; Leung, Kelvin K. ; Sudre, Carole H. ; Ourselin, Sebastien ; Biessels, Geert Jan ; Carmichael, Owen T. ; Fox, Nick C. ; Cardoso, M. Jorge ; Barnes, Josephine ; for the Alzheimer's Disease Neuroimaging Initiative. / White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy. In: Hippocampus. 2017 ; Vol. 27, No. 3. pp. 249-262.
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