White matter integrity and vulnerability to Alzheimer's disease: Preliminary findings and future directions

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123 Scopus citations


Neuroimaging biomarkers that precede cognitive decline have the potential to aid early diagnosis of Alzheimer's disease (AD). A body of diffusion tensor imaging (DTI) work has demonstrated declines in white matter (WM) microstructure in AD and its typical prodromal state, amnestic mild cognitive impairment. The present review summarizes recent evidence suggesting that WM integrity declines are present in individuals at high AD-risk, prior to cognitive decline. The available data suggest that AD-risk is associated with WM integrity declines in a subset of tracts showing decline in symptomatic AD. Specifically, AD-risk has been associated with WM integrity declines in tracts that connect gray matter structures associated with memory function. These tracts include parahippocampal WM, the cingulum, the inferior fronto-occipital fasciculus, and the splenium of the corpus callosum. Preliminary evidence suggests that some AD-risk declines are characterized by increases of radial diffusivity, raising the possibility that a myelin-related pathology may contribute to AD onset. These findings justify future research aimed at a more complete understanding of the neurobiological bases of DTI-based declines in AD. With continued refinement of imaging methods, DTI holds promise as a method to aid identification of presymptomatic AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Original languageEnglish
Pages (from-to)416-422
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number3
StatePublished - Mar 2012

Bibliographical note

Funding Information:
We gratefully acknowledge our collaborators at the Alzheimer's Disease Research Center, and Magnetic Resonance Imaging and Spectroscopy Center at the University of Kentucky. This review was supported by NINDS Grant R01 NS-36660 , NIA Grant R01 AG033036 and NSF Grant BCS-0814302 .


  • APOE
  • Alzheimer's
  • Alzheimer's risk
  • DTI
  • Diffusion tensor imaging
  • Presymptomatic

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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