Rojas et al. (2018) discovered a higher prevalence of WMH in homozygous APOE-ε4 allele carriers aged 45–75 years. In non-genetic forms of AD, this link has been less documented and WMH are only associated with severity of AD. Temporal areas and parahippocampus/hippocampus are the first regions affected in AD. It has been hypothesized that the presence of high WMH and the decrease of gray matter in key brain areas may be viewed as prodromal signs of AD as suggested in the literature (Wolf et al., 2000; Vermeer et al., 2003; Prins et al., 2004). The gene discussed is APOE; the disease is Alzheimer disease.