Although the specific mechanisms of how WMH volume influences gray matter atrophy in aging is unknown, it is possible that increases of WMH volumes in left temporal and right parietal regions with age may influence ischemia-related brain differences, such as hippocampal disconnection and axonal loss via Wallerian degeneration (Schmidt et al., 2011) or tau hyperphosphorylation (Zlokovic, 2011), resulting in hippocampal volume reductions. Here, MAPT is linked to ischemia.