Relationship between multimodal neuroimaging biomarkers and white matter hyperintensities across the Alzheimer’s disease spectrum: A region‐of‐interest‐ and voxel‐based study

Background White matter hyperintensities (WMH) are a frequent marker of cognitive impairment and Alzheimer’s disease (AD). Although WMH have been commonly linked to cerebrovascular disease, recent studies suggest an association between AD pathology and regional WMH distribution. The objective of this study was to investigate the relationship of AD neuroimaging biomarkers of Aß burden, hypometabolism and GM atrophy with regional WMH distribution in older adults across the cognitive continuum at two different levels: regions of interest (ROIs) and voxel. Method FLAIR MRI (1), AV45‐PET (2), FDG‐PET (3) and T1 MRI (4), were acquired in 155 participants with normal cognition, subjective cognitive decline, mild cognitive impairment and clinical AD in the IMAP cohort (Caen, France). WMH were segmented using FLAIR MRI with the SPM12‐based lesion‐segmentation‐tool (Schmidt, 2017). Standard pipelines were applied to WMH probability maps and all other images (2‐4) resulting in maps normalized in MNI space. Mean AV45‐SUVR, mean FDG‐SUVR and total GMV were extracted within AD signature templates (Besson et al., 2015). Moreover, regional WMH were computed in multiple ROIs based on previous recommendations (Wardlaw et al., 2013). The associations between AD biomarkers levels and regional WMH distribution were assessed using linear regression models at ROI and voxel levels, adjusting for age, sex, education and blood pressure. Uncorrected p<.05 and p<.005, respectively for ROI‐ and voxel‐wise analyses, were applied. Result For the ROI analysis (Table 1), mean AV45‐SUVR was not significantly associated with regional WMH. Mean FDG‐SUVR was negatively related with regional WMH, including periventricular region and corpus callosum (body and splenium). Finally, GMV in the AD signature was found to be significantly associated with WMH in all ROIs (Table 1). For the voxel‐based analyses, the results are comparable (Figure 2B.‐D.). Notably, a positive association was found between the mean AV45 SUVR and the splenium part of the corpus callosum (Figure 2.D). Conclusion Our findings confirm that AD neuroimaging biomarkers of Aß burden, hypometabolism and GM atrophy are associated with regional WMH, including periventricular regions and posterior parts of the corpus callosum. These associations might reflect either involvement of vascular damage in AD pathogenesis or contribution of AD pathology to white matter damage.