White matter diffusion alterations in normal women at risk of Alzheimer's disease

Charles D. Smith, Himachandra Chebrolu, Anders H. Andersen, David A. Powell, Mark A. Lovell, Shuling Xiong, Brian T. Gold

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal fasciculi (particularly posteriorly), the splenium of the corpus callosum, subcallosal white matter and the cingulum bundle. These findings demonstrate that specific white matter pathways are altered in normal women at increased risk of AD years before the expected onset of cognitive symptoms.

Original languageEnglish
Pages (from-to)1122-1131
Number of pages10
JournalNeurobiology of Aging
Issue number7
StatePublished - Jul 2010

Bibliographical note

Funding Information:
This study was supported by NINDS Grant R01 NS-36660. We thank Agnes Bognar, R.T., Kim Wilson, B.A., LuAnn Hamon, B.A., Dorothy Ross, B.A., and Barbara Martin, B.A. for their invaluable assistance in recruiting, scanning and testing the participants, and for treating them professionally and so well.


  • Alzheimer's disease
  • Apolipoprotein E
  • Diffusion tensor
  • Fractional anisotropy
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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