However, we analyzed the interaction of DM with APOE4 on global cognition in middle age and older age, i.e., midlife DM and late-life DM, based on the evidence of two significant lifetime periods vulnerable to AD and related cognitive decline (Mayor, 2014; Harvard Health Letter, 2015; Koekkoek et al., 2015; Gottesman et al., 2017; Sadahiro et al., 2019; Hu et al., 2020; Wang and Liu, 2021; Noguchi-Shinohara et al., 2022). This evidence concerns the gene APOE and diabetes mellitus.