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.

Topographical differences in white matter hyperintensity burden and cognition in aging, MCI, and AD

“…Several previous studies have observed an association between cognitive functioning and WMH burden in aging, cognitive decline, MCI, and AD. However, the results of these studies have been inconsistent and most examine total instead of regional WMH burden [13,18,[20][21][22]24,25]. Our results show that change in cognition (global functioning, executive functioning, and memory) for NCs was associated with total, frontal, temporal, parietal, and occipital WMH burden.…”

“…That is, WMHs are lower in cognitively unimpaired older adults (NC) and progressively increase from MCI to AD [6]. Research examining WMH burden tends to measure global WMH burden as opposed to regional WMH burden (e.g., Brugulat-Serrat et al, 2020; Garnier-Crussard et al, 2022). The studies that have observed healthy older adults and MCI/AD group differences in regional WMH burden have found differences in all regions.…”

“…The studies that have observed healthy older adults and MCI/AD group differences in regional WMH burden have found differences in all regions. For instance, some studies report that the largest NC-AD group difference in WMH volume is observed in the parietal, temporal, or occipital regions [13][14][15]. However, previous research notes that WMHs are mostly distributed in both the parietal and frontal lobes [15,16], with MCI and AD patients also showing increased WMHs in frontal regions relative to controls [15].…”

Vascular Health Is Associated With Functional Connectivity Decline in Higher-Order Networks of Older Adults

“…The HbA1c level were measured after participants underwent a fasting blood draw. The measures were reported in our previous studies ( Garnier-Crussard et al, 2020 , 2021 ) and corresponds to the 3-month averaged blood sugar level and is related to diabetes mellitus risk. Vascular risk factors were all assessed at baseline.…”

“…The WMH volumes were derived using probability maps, which were computed from segmented FLAIR images using the lesion prediction algorithm (LPA), implemented in the Lesion Segmentation Toolbox (LST 2 , version 2) of SPM12. As described in our previous studies ( Garnier-Crussard et al, 2020 , 2021 ; Gaubert et al, 2021 ), processing comprised the co-registration of individual raw FLAIR images to their respective T1-weighted image and the computation of native-space lesion probability maps. To quantify WMH volumes, native-space lesion probability maps were binarized at a threshold at 0.5 and a minimal cluster size of 10 mm 3 .…”