White matter hyperintensity topography in Alzheimer's disease and links to cognition

Introduction White matter hyperintensities (WMH) are often described in Alzheimer's disease (AD), but their topography and specific relationships with cognition remain unclear. Methods Regional WMH were estimated in 54 cognitively impaired amyloid beta-positive AD (A beta pos-AD), compared to 40 cognitively unimpaired amyloid beta-negative older controls (A beta neg-controls) matched for vascular risk factors. The cross-sectional association between regional WMH volume and cognition was assessed within each group, controlling for cerebral amyloid burden, global cortical atrophy, and hippocampal atrophy. Results WMH volume was larger in A beta pos-AD compared to A beta neg-controls in all regions, with the greatest changes in the splenium of the corpus callosum (S-CC). In A beta pos-AD patients, larger total and regional WMH volume, especially in the S-CC, was strongly associated with decreased cognition. Discussion WMH specifically contribute to lower cognition in AD, independently from amyloid deposition and atrophy. This study emphasizes the clinical relevance of WMH in AD, especially posterior WMH, and most notably S-CC WMH.