White matter changes in preclinical Alzheimer's disease: a magnetic resonance imaging-diffusion tensor imaging study on cognitively normal older people with positive amyloid β protein 42 levels

Neurobiol Aging. 2014 Dec;35(12):2671-2680. doi: 10.1016/j.neurobiolaging.2014.05.027. Epub 2014 Jun 6.


The aim of this study was to use diffusion tensor imaging measures to determine the existence of white matter microstructural differences in the preclinical phases of Alzheimer's disease, assessing cognitively normal older individuals with positive amyloid β protein (Aβ42) levels (CN_Aβ42+) on the basis of normal cognition and cerebrospinal fluid Aβ42 levels below 500 pg/mL. Nineteen CN_Aβ42+ and 19 subjects with Aβ42 levels above 500 pg/mL (CN_Aβ42-) were included. We encountered increases in axial diffusivity (AxD) in CN_Aβ42+ relative to CN_Aβ42- in the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus bilaterally, and also in the left fornix, left uncinate fasciculus, and left inferior fronto-occipital fasciculus. However, no differences were found in other diffusion tensor imaging indexes. Cognitive reserve scores were positively associated with AxD exclusively in the CN_Aβ42+ group. The finding of AxD alteration together with preserved fractional anisotropy, mean diffusivity, and radial diffusivity indexes in the CN_Aβ42+ group may indicate that, subtle axonal changes may be happening in the preclinical phases of Alzheimer's disease, whereas white matter integrity is still widely preserved.

Keywords: Alzheimer's disease; Cerebrospinal fluid; Cognition; Diagnosis; Diffusion tensor imaging; Preclinical phases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / psychology*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Amyloid beta-Peptides / metabolism*
  • Anisotropy
  • Brain / metabolism
  • Cognition / physiology*
  • Diffusion Magnetic Resonance Imaging*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Peptide Fragments / metabolism*
  • White Matter / pathology*


  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)