Topographic patterns of white matter hyperintensities are associated with multimodal neuroimaging biomarkers of Alzheimer's disease

• Published in: Alzheimer's Research & Therapy 2021, Vol.13 (1)
• Main Authors: Gaubert, Malo, Lange, Catharina, Garnier-Crussard, Antoine, Köbe, Theresa, Bougacha, Salma, Gonneaud, Julie, de Flores, Robin, Tomadesso, Clémence, Mézenge, Florence, Landeau, Brigitte, de la Sayette, Vincent, Chételat, Gaël, Wirth, Miranka
• Format: Report
• Language: English
• Subjects: Alzheimer's disease; Amyloid beta-protein; Development and progression; Health aspects; Methods; Neuroimaging; PET imaging; Physiological aspects
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-020-00759-3

White matter hyperintensities (WMH) are frequently found in Alzheimer's disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (A[beta]) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with A[beta] burden, glucose hypometabolism, and gray matter volume reduction. In a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical A[beta] deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure. There were no significant associations between global A[beta] burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater A[beta] deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas. This study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Ass deposition and neurodegeneration.