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Divergent functional connectivity changes associated with white matter hyperintensities.

Alexander F Santillo1, Tor O Strandberg1, Nina H Reislev2

  • 1Department of Clinical Sciences, Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund/Malmö, Sweden. Postal address: Memory Clinic, Skåne University Hospital, SE-20502 Malmö, Sweden.

Neuroimage
|June 8, 2024
PubMed
Summary
This summary is machine-generated.

Age-related white matter hyperintensities disrupt brain connectivity and cognitive function. Novel mechanisms reveal increased frontal lobe connectivity linked to cognitive decline, impacting processing speed and executive function.

Keywords:
Cognitive functionDiffusion mriFunctional connectivityWhite matter hyperintensitiesentropy

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Area of Science:

  • Neuroimaging
  • Cognitive Neuroscience
  • Gerontology

Background:

  • Age-related white matter hyperintensities (WMH) are common and linked to cognitive decline.
  • The precise mechanisms by which WMH affect brain structure, function, and cognition remain incompletely understood.

Purpose of the Study:

  • To investigate the mechanistic links between white matter hyperintensities, structural and functional brain connectivity, and cognitive performance in non-demented individuals.
  • To explore novel mechanisms of cognitive impairment associated with WMH.

Main Methods:

  • Analysis of multimodal MRI data (FLAIR, DTI, fMRI) from 465 non-demented participants (334 cognitively normal, 131 with mild cognitive impairment).
  • Quantification of WMH, estimation of diffusion tensor imaging parameters, and calculation of resting-state functional connectivity (FC).
  • Assessment of cognitive functions including executive function and processing speed; functional changes examined using sample entropy.

Main Results:

  • WMH were associated with reduced structural white matter integrity and decreased interregional functional connectivity.
  • Reduced interregional connectivity correlated with poorer executive function and processing speed.
  • WMH were also linked to increased intraregional frontal lobe connectivity, associated with reduced cognitive performance and increased signal entropy.

Conclusions:

  • White matter hyperintensities impact cognition through both disrupted interregional and altered intraregional connectivity.
  • Increased frontal lobe functional connectivity, characterized by higher signal entropy, represents a novel mechanism linking WMH to cognitive deficits.
  • These findings enhance understanding of the complex effects of white matter lesions on cognitive function beyond established pathways.