Cortical microstructural changes along the Alzheimer's disease continuum

Alzheimers Dement. 2018 Mar;14(3):340-351. doi: 10.1016/j.jalz.2017.09.013. Epub 2017 Oct 31.


Introduction: Cortical mean diffusivity (MD) and free water fraction (FW) changes are proposed biomarkers for Alzheimer's disease (AD).

Methods: We included healthy control subjects (N = 254), mild cognitive impairment (N = 41), and AD dementia (N = 31) patients. Participants underwent a lumbar puncture and a 3 T magnetic resonance imaging. Healthy control subjects were classified following National Institute on Aging-Alzheimer's Association stages (stage 0, N = 220; stage 1, N = 25; and stage 2/3, N = 9). We assessed the cortical MD, cortical FW, and cortical thickness (CTh) changes along the AD continuum.

Results: Microstructural and macrostructural changes show a biphasic trajectory. Stage 1 subjects showed increased CTh and decreased MD and FW with respect the stage 0 subjects. Stage 2/3 subjects showed decreased CTh and increased cortical MD and FW, changes that were more widespread in symptomatic stages.

Discussion: These results support a biphasic model of changes in AD, which could affect the selection of patients for clinical trials and the use of magnetic resonance imaging as a surrogate marker of disease modification.

Keywords: Alzheimer's disease continuum; Amyloid; Biomarkers; CSF; Cortical microstructure; MRI; Tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / genetics
  • Apolipoproteins E / genetics
  • Biomarkers / cerebrospinal fluid
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / pathology
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / genetics
  • Disease Progression
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organ Size
  • Spinal Puncture


  • Apolipoproteins E
  • Biomarkers