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Connectome gradient dysfunction contributes to white matter hyperintensity-related cognitive decline.

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White matter hyperintensity (WMH) volume reduction impacts brain network gradients and cognitive decline. Specifically, WMH progression narrows the primary-to-transmodal gradient, impairing executive function and processing speed.

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Area of Science:

  • Neuroimaging
  • Cognitive Neuroscience
  • Neurology

Background:

  • White matter hyperintensity (WMH) is linked to cognitive decline, but underlying mechanisms are unclear.
  • Functional brain networks exhibit a primary-to-transmodal gradient from sensation to cognition.
  • It remains unknown how WMH progression alters this gradient and affects cognition.

Purpose of the Study:

  • To investigate the relationship between WMH volume and functional connectome gradient structure.
  • To explore how alterations in the primary-to-transmodal gradient are associated with cognitive function in WMH individuals.

Main Methods:

  • Utilized resting-state functional MRI (rs-fMRI) in 758 WMH individuals.
  • Reconstructed functional connectome gradients using a gradient decomposition framework.
  • Analyzed associations between WMH distribution, gradient measures, and cognitive domains.

Main Results:

  • Increased WMH volume correlated with poorer executive function and processing speed.
  • WMH progression reduced the range and variance of the primary-to-transmodal gradient.
  • A narrower gradient range and smaller variance were linked to poorer executive function.

Conclusions:

  • WMH volume, primary-to-transmodal gradient, and cognition are interconnected.
  • WMH negatively impacts executive function, partly mediated by reduced gradient differentiation.
  • Findings highlight the role of altered brain network organization in WMH-related cognitive impairment.