Strategic white matter hyperintensity locations for cognitive impairment: A multicenter lesion-symptom mapping study in 3525 memory clinic patients

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Abstract

INTRODUCTION: Impact of white matter hyperintensities (WMH) on cognition likely depends on lesion location, but a comprehensive map of strategic locations is lacking. We aimed to identify these locations in a large multicenter study.

METHODS: Individual patient data (n = 3525) from 11 memory clinic cohorts were harmonized. We determined the association of WMH location with attention and executive functioning, information processing speed, language, and verbal memory performance using voxel-based and region of interest tract-based analyses.

RESULTS: WMH in the left and right anterior thalamic radiation, forceps major, and left inferior fronto-occipital fasciculus were significantly related to domain-specific impairment, independent of total WMH volume and atrophy. A strategic WMH score based on these tracts inversely correlated with performance in all domains.

DISCUSSION: The data show that the impact of WMH on cognition is location-dependent, primarily involving four strategic white matter tracts. Evaluation of WMH location may support diagnosing vascular cognitive impairment.

HIGHLIGHTS: We analyzed white matter hyperintensities (WMH) in 3525 memory clinic patients from 11 cohorts The impact of WMH on cognition depends on location We identified four strategic white matter tracts A single strategic WMH score was derived from these four strategic tracts The strategic WMH score was an independent determinant of four cognitive domains.

Original languageEnglish
Pages (from-to)2420-2432
Number of pages13
JournalAlzheimer's & Dementia
Volume19
Issue number6
Early online date12 Dec 2022
DOIs
Publication statusPublished - Jun 2023

Keywords

  • cognitive impairment
  • lesion symptom mapping
  • location
  • memory clinic patients
  • white matter hyperintensities

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