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 (Aβpos-AD), compared to 40 cognitively unimpaired amyloid beta-negative older controls (Aβneg-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 Aβpos-AD compared to Aβneg-controls in all regions, with the greatest changes in the splenium of the corpus callosum (S-CC). In Aβpos-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.