Linking cortical atrophy to white matter hyperintensities of presumed vascular origin

J Cereb Blood Flow Metab. 2021 Jul;41(7):1682-1691. doi: 10.1177/0271678X20974170. Epub 2020 Dec 1.

Abstract

We examined the relationship between white matter hyperintensities (WMH) and cortical neurodegeneration in cerebral small vessel disease (CSVD) by investigating whether cortical thickness is a remote effect of WMH through structural fiber tract connectivity in a population at increased risk of CSVD. We measured cortical thickness on T1-weighted images and segmented WMH on FLAIR images in 930 participants of a population-based cohort study at baseline. DWI-derived whole-brain probabilistic tractography was used to define WMH connectivity to cortical regions. Linear mixed-effects models were applied to analyze the relationship between cortical thickness and connectivity to WMH. Factors associated with cortical thickness (age, sex, hemisphere, region, individual differences in cortical thickness) were added as covariates. Median age was 64 [IQR 46-76] years. Visual inspection of surface maps revealed distinct connectivity patterns of cortical regions to WMH. WMH connectivity to the cortex was associated with reduced cortical thickness (p = 0.009) after controlling for covariates. This association was found for periventricular WMH (p = 0.001) only. Our results indicate an association between WMH and cortical thickness via connecting fiber tracts. The results imply a mechanism of secondary neurodegeneration in cortical regions distant, yet connected to subcortical vascular lesions, which appears to be driven by periventricular WMH.

Keywords: Cerebral small vessel disease; cortical thickness; diffusion-weighted imaging; structural connectivity; white matter hyperintensities.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrophy / etiology
  • Atrophy / pathology*
  • Cerebral Cortex / pathology*
  • Cerebral Small Vessel Diseases / complications*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / pathology*
  • Prospective Studies
  • White Matter / pathology*