High white matter lesion load is associated with hippocampal atrophy in mild cognitive impairment

Dement Geriatr Cogn Disord. 2011;31(2):132-8. doi: 10.1159/000323014. Epub 2011 Feb 3.


Background: Mild cognitive impairment (MCI) is a heterogeneous condition suggested as a prodromal state of Alzheimer's disease (AD) and subcortical vascular dementia (SVD). Recent findings suggest that white matter lesions (WML) may be associated with hippocampal atrophy. The objective of the study was to examine hippocampal and WML volumes in MCI patients and to examine if WML were linked to hippocampal atrophy.

Methods: The Gothenburg MCI study is a clinically based longitudinal study with biennial clinical assessments. The participants (n = 166) consist of 92 patients with stable MCI, 30 patients with converting MCI, and 44 healthy controls. WML volumes was measured manually using MRIcron. Automated segmentation of hippocampal and total white matter volumes was performed using FreeSurfer.

Results: The patients converting from MCI to dementia had reduced hippocampal volume. Stable MCI patients had fewer WML and converting MCI patients had more WML compared to controls. Hippocampal volume was only correlated to WML volume (ρ = 0.57; p < 0.01) in the quartile (n = 42) with the most WML.

Conclusions: Hippocampal atrophy is present in both AD and SVD. Hippocampal volume was associated with WML volume only in the high WML quartile, suggesting that the WML volume must reach a threshold before hippocampal atrophy is seen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Apolipoproteins E / genetics
  • Atrophy
  • Brain / pathology*
  • Cognition Disorders / pathology*
  • Cognition Disorders / psychology
  • Dementia, Vascular / pathology
  • Dementia, Vascular / psychology
  • Educational Status
  • Female
  • Hippocampus / pathology*
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests


  • Apolipoproteins E