Previous studies have suggested that DM and APOE4 are major risk factors for AD and related cognitive decline, and there are many reports that each has a significant association with cognitive decline (Morris et al., 2010; Liu et al., 2013; Jayaraman and Pike, 2014; Lowe et al., 2014; Koekkoek et al., 2015; Gonzalez-Reyes et al., 2016; Shinohara and Sato, 2017; Sutherland et al., 2017; Zhao et al., 2017; Yamazaki et al., 2019; Beeri and Bendlin, 2020; Hu et al., 2020; Jeon et al., 2020; Shinohara et al., 2020; Rasool et al., 2021; Noguchi-Shinohara et al., 2022). This evidence concerns the gene APOE and Alzheimer disease.