Given that APOE is a key molecule in lipid metabolism that plays an important role in the pathogenesis of cognitive impairment, in the present study, we aimed to explore the potential link between APOE-mediated lipid metabolic regulation and the shared pathological mechanisms of the three categories of cognitive impairment (AD, DCI, and VD), including Aβ protein deposition, tau protein hyperphosphorylation, and insulin resistance. This evidence concerns the gene APOE and Alzheimer disease.