Accumulating evidence implicates small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on T2-weighted MRI, in the pathogenesis and diagnosis of Alzheimer's disease (AD). Cross-sectional volumetric measures of WMH, particularly in the parietal lobes, are associated with increased risk of AD. In the current study, we sought to determine whether the longitudinal regional progression of WMH predicts incident AD above-and-beyond traditional radiological markers of neurodegeneration (i.e., hippocampal atrophy, cortical thickness). Three hundred three non-demented older adults (mean age = 79.24±5.29) received high-resolution MRI at baseline and then again 4.6 years (SD=1.01) later. Over the follow-up interval 26 participants progressed to AD. Using structural equation modeling (SEM), we calculated latent difference scores of parietal/non-parietal WMH, hippocampus volumes, and cortical thickness values in ADrelated regions. Within the SEM framework, we determined whether baseline or change scores or both predicted AD conversion, while controlling for several time-invariant relevant variables. Smaller baseline hippocampus volume, change in hippocampus volume (i.e., atrophy), higher baseline parietal lobe WMH, and increasing parietal lobe WMH volume but not WMH in other regions or measures of cortical thickness, independently predicted progression to AD. The findings provide strong evidence that regionally accumulating WMH, in addition to degenerative changes in the medial temporal lobe, predict AD onset in addition to hallmark neurodegenerative changes typically associated with AD
