Accelerated decline in white matter integrity in clinically normal individuals at risk for Alzheimer's disease

Neurobiol Aging. 2016 Jun;42:177-88. doi: 10.1016/j.neurobiolaging.2016.03.016. Epub 2016 Mar 21.


Prior studies have identified white matter abnormalities in Alzheimer's disease (AD). Yet, cross-sectional studies in normal older individuals show little evidence for an association between markers of AD risk (APOE4 genotype and amyloid deposition), and white matter integrity. Here, 108 normal older adults (age, 66-87) with assessments of apolipoprotein e4 (APOE4) genotype and assessment of amyloid burden by positron emission tomography underwent diffusion tensor imaging scans for measuring white matter integrity at 2 time points, on average 2.6 years apart. Linear mixed-effects models showed that amyloid burden at baseline was associated with steeper decline in fractional anisotropy in the parahippocampal cingulum (p < 0.05). This association was not significant between baseline measures suggesting that longitudinal analyses can provide novel insights that are not detectable in cross-sectional designs. Amyloid-related changes in hippocampus volume did not explain the association between amyloid burden and change in fractional anisotropy. The results suggest that accumulation of cortical amyloid and white matter changes in parahippocampal cingulum are not independent processes in individuals at increased risk for AD.

Keywords: Aging; Amyloid; Diffusion tensor imaging; Longitudinal; White matter.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / pathology
  • Alzheimer Disease* / etiology
  • Amyloid beta-Peptides / metabolism
  • Apolipoproteins E / genetics
  • Diffusion Tensor Imaging
  • Female
  • Genotype
  • Hippocampus / diagnostic imaging
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Male
  • Risk
  • White Matter / diagnostic imaging*
  • White Matter / metabolism
  • White Matter / pathology*


  • Amyloid beta-Peptides
  • Apolipoproteins E