APOE and dementia: Therefore, several issues on SVD load and cognitive phenotypes remain to be clarified: (1) whether various SVD markers, which represent different dominant pathologies such as intrinsic arteriolar disease (lacunes and WMH) and neurodegeneration (hippocampal atrophy), have differential effects on cognition is unclear; (2) the extent to which the association of SVD load with cognitive phenotypes is attributed to subsequent structural brain changes is unknown; and (3) whether APOE ε4 interacts with SVD load to affect cognitive decline and dementia has yet to be determined.