Changes in white matter integrity before conversion from mild cognitive impairment to Alzheimer's disease

PLoS One. 2014 Aug 25;9(8):e106062. doi: 10.1371/journal.pone.0106062. eCollection 2014.

Abstract

Background: Mild cognitive impairment (MCI) may represent an early stage of dementia conferring a particularly high annual risk of 15-20% of conversion to Alzheimer's disease (AD). Recent findings suggest that not only gray matter (GM) loss but also a decline in white matter (WM) integrity may be associated with imminent conversion from MCI to AD.

Objective: In this study we used Voxel-based morphometry (VBM) to examine if gray matter loss and/or an increase of the apparent diffusion coefficient (ADC) reflecting mean diffusivity (MD) are an early marker of conversion from MCI to AD in a high risk population.

Method: Retrospective neuropsychological and clinical data were collected for fifty-five subjects (MCI converters n = 13, MCI non-converters n = 14, healthy controls n = 28) at baseline and one follow-up visit. All participants underwent diffusion weighted imaging (DWI) and T1-weighted structural magnetic resonance imaging scans at baseline to analyse changes in GM density and WM integrity using VBM.

Results: At baseline MCI converters showed impaired performance in verbal memory and naming compared to MCI non-converters. Further, MCI converters showed decreased WM integrity in the frontal, parietal, occipital, as well as the temporal lobe prior to conversion to AD. Multiple regression analysis showed a positive correlation of gray matter atrophy with specific neuropsychological test results.

Conclusion: Our results suggest that additionally to morphological changes of GM a reduced integrity of WM indicates an imminent progression from MCI stage to AD. Therefore, we suggest that DWI is useful in the early diagnosis of AD.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Alzheimer Disease / pathology*
  • Atrophy / pathology
  • Brain Mapping / methods
  • Case-Control Studies
  • Cognitive Dysfunction / pathology*
  • Disease Progression
  • Female
  • Gray Matter / pathology
  • Humans
  • Male
  • Neuropsychological Tests
  • Retrospective Studies
  • White Matter / pathology*

Grants and funding

The authors have no funding or support to report.