Longitudinal brain structural changes in preclinical Alzheimer's disease

Alzheimers Dement. 2017 May;13(5):499-509. doi: 10.1016/j.jalz.2016.08.010. Epub 2016 Sep 28.

Abstract

Introduction: Brain structural changes in preclinical Alzheimer's disease (AD) are poorly understood.

Methods: We compared the changes in cortical thickness in the ADNI cohort during a 2-year follow-up between the NIA-AA preclinical AD stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed the correlation between baseline CSF biomarkers and cortical atrophy rates.

Results: At follow-up, stage 1 subjects showed reduced atrophy rates in medial frontal areas and precuneus compared to stage 0 subjects, whereas stage 2/3 subjects presented accelerated atrophy in medial temporal structures. Low CSF Aβ1-42 levels were associated with reduced atrophy rates in subjects with normal tau levels and high CSF tau levels with accelerated atrophy only in subjects with low Aβ1-42 levels.

Discussion: Our longitudinal data confirm a biphasic trajectory of changes in brain structure in preclinical AD. These have implications in AD trials, both in patient selection and the use of MRI as a surrogate marker of efficacy.

Keywords: Alzheimer's disease; Amyloid; Biomarkers; CSF; Longitudinal; MRI; Tau.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Atrophy / pathology*
  • Biomarkers / cerebrospinal fluid
  • Brain / pathology*
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Peptide Fragments / cerebrospinal fluid
  • Prodromal Symptoms*
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • tau Proteins