A novel approach to quantifying longitudinal white matter hyperintensity morphometrics with Alzheimer disease progression

Abstract

AbstractBackgroundThe role of cerebrovascular damage in Alzheimer’s Disease (AD) has resulted in inconsistent findings particularly when analyzing longitudinal data. We introduce WMH shape analysis (WSA) that quantifies white matter hyperintensity (WMH) expansion as the distance from lesion voxels to a region of interest boundary. We sought to examine the extent and spatial topography of WMH expansion with progression to AD.MethodFluid‐Attenuated Inversion Recovery (FLAIR) images were extracted across two timepoints from ADNI. 275 longitudinal participants were classified into groups based on amyloid and cognitive status: 99 controls (CN), 42 amyloid positive cognitively stable preclinical (PC) AD, and 134 amyloid positive cognitively impaired AD individuals. WSA was performed on 5 WMH clusters (juxtacortical, anterior corona radiata, periventricular, parietal, and occipital/posterior horn). The intensity value for each cluster ROI boundary voxels reflects the Euclidean Distance from a voxel to the closest WMH voxel. The difference in distances (DD) for each timepoint provides a metric of WMH expansion. A voxel‐wise omnibus ANOVA was performed across all three groups followed by subsequent T‐tests. Additionally, we evaluated the relationship between the changes in DD maps with PET amyloid summary values, hypertension, and APOE e4 status.ResultWMH expansion was found to be significant across three groups (Fig. 1) and was primarily within two WMH clusters (p<0.05 corrected). T‐tests revealed that the AD group had significantly greater expansion in the juxtacortical cluster compared to CN but not the PC group (p<0.05 corrected). However, for the posterior horn that difference was driven by the PC with greater WMH expansion compared to either the AD or CN group (p<0.05 corrected). A significant association was observed with amyloid in the juxtacortical cluster but not with hypertension. A strong trend (p = 0.06 corrected) was observed for APOE e4 status in the juxtacortical cluster associating with more copies of the e4 allele.ConclusionThis new approach to quantifying and analyzing WMH longitudinal expansion revealed different patterns of expansion with increased AD severity. These results implicate that WMH growth associated with AD progression is spatially specific and grows in distinct ways throughout the disease process.