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

Abstract

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.

Keywords: Alzheimer's disease; amyloid positron emission tomography; cognition; corpus callosum; executive functions; fluid-attenuated inversion recovery; magnetic resonance imaging; memory; splenium; white matter hyperintensities.

FIGURE 1

Examples of periventricular white matter hyperintensities (WMH) and subependymal WMH in the region of the splenium of the corpus callosum (S‐CC). The image on the left corresponds to the axial T2‐weighted fluid‐attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) of a 72‐year‐old amyloid beta–positive Alzheimer's disease (Aβpos‐AD) woman with mild cognitive impairment. The image on the right corresponds to the axial T2‐weighted FLAIR MRI of a 54‐year‐old Aβpos‐AD man with dementia. Yellow arrows show mild periventricular WMH and red arrows show subependymal hyperintensities in the region of the S‐CC

FIGURE 2

Associations between global cognition and regional white matter hyperintensities (WMH) in amyloid beta–positive Alzheimer's disease (Aβpos‐AD). Association between regional WMH and global cognition (Mattis Dementia Rating Scale [DRS]). Plots represent global cognition regressed onto regional WMH (total intracranial volume–corrected and log‐transformed), controlling for age, sex, level of education (with 95% confidence intervals). Standardized betas (β) were added. For the sake of illustration one outlier (Mattis‐DRS = 84/144) was removed from the figure (results were unchanged with or without the outlier). Anatomic atlases were represented on the left panel for illustration purposes (Hammers atlas for lobes at the top and JHU atlas for CC at the bottom)