In line with this notion, previous observational studies indicated that APOE4 and HTN act synergistically to influence cognitive performance, subcortical white matter integrity, and cortical amyloid accumulation (Peila et al., 2001; De Leeuw et al., 2004; De Frias et al., 2014; Oberlin et al., 2015; Jeon et al., 2019). This evidence concerns the gene APOE and hypertensive disorder.