Selective changes in white matter integrity in MCI and older adults with cognitive complaints

Yang Wang, John D. West, Laura A. Flashman, Heather A. Wishart, Robert B. Santulli, Laura A. Rabin, Nadia Pare, Konstantinos Arfanakis, Andrew J. Saykin

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


Background: White matter changes measured using diffusion tensor imaging have been reported in Alzheimer's disease and amnestic mild cognitive impairment, but changes in earlier pre-mild cognitive impairment stages have not been fully investigated. Methods: In a cross-sectional analysis, older adults with mild cognitive impairment (n. = 28), older adults with cognitive complaints but without psychometric impairment (n. = 29) and healthy controls (n. = 35) were compared. Measures included whole-brain diffusion tensor imaging, T1-weighted structural magnetic resonance imaging, and neuropsychological assessment. Diffusion images were analyzed using Tract-Based Spatial Statistics. Voxel-wise fractional anisotropy and mean, axial, and radial diffusivities were assessed and compared between groups. Significant tract clusters were extracted in order to perform further region of interest comparisons. Brain volume was estimated using FreeSurfer based on T1 structural images. Results: The mild cognitive impairment group showed lower fractional anisotropy and higher radial diffusivity than controls in bilateral parahippocampal white matter. When comparing extracted diffusivity measurements from bilateral parahippocampal white matter clusters, the cognitive complaint group had values that were intermediate to the mild cognitive impairment and healthy control groups. Group difference in diffusion tensor imaging measures remained significant after controlling for hippocampal atrophy. Across the entire sample, diffusion tensor imaging indices in parahippocampal white matter were correlated with memory function. Conclusions: These findings are consistent with previous results showing changes in parahippocampal white matter in Alzheimer's disease and mild cognitive impairment compared to controls. The intermediate pattern found in the cognitive complaint group suggests the potential of diffusion tensor imaging to contribute to earlier detection of neurodegenerative changes during prodromal stages. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Original languageEnglish (US)
Pages (from-to)423-430
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number3
StatePublished - Mar 2012


  • Alzheimer's disease
  • Diffusion tensor imaging
  • Diffusivity
  • Hippocampus
  • Memory
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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