Multimodal imaging evidence for axonal and myelin deterioration in amnestic mild cognitive impairment

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15 Scopus citations


White matter (WM) microstructural declines have been demonstrated in Alzheimer's disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using voxel based morphometry. After controlling for WM atrophy, the main pattern of TBSS findings indicated reduced fractional anisotropy with only small alterations in mean diffusivity/radial diffusivity/axial diffusivity. These WM microstructural declines bordered and/or were connected to gray matter structures showing volumetric declines. However, none of the potential relationships between WM integrity and volume in connected gray matter structures was significant, and adding fractional anisotropy information improved the classificatory accuracy of aMCI compared to the use of hippocampal atrophy alone. These results suggest that WM microstructural declines provide unique information not captured by atrophy measures that may aid the magnetic resonance imaging contribution to aMCI detection.

Original languageEnglish
Pages (from-to)S19-S31
JournalJournal of Alzheimer's Disease
Issue numberSUPPL. 3
StatePublished - 2012

Bibliographical note

Funding Information:
This research was supported by grants from the National Science Foundation (PCM 78-15835 to J.P.T. and a graduate fellowship to R.S.), the Science Research Council, U.K. (to R.J.C.) and the University of California Research Committee. We wish to thank Mrs. I. Durrant and Mr. J. McMurray for technical help, Dr. Mary Ann Markwell for generous gifts of protein markers and Dr. John P. Markwell for advice during the course of this work. Deriphat 160 was a gift from Henkel Corporation, Chicago, IL.


  • Alzheimer's disease
  • atrophy
  • diffusion tensor imaging
  • mild cognitive impairment

ASJC Scopus subject areas

  • Neuroscience (all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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