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

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