Multivariable logistic regression analysis indicated that serum apelin (OR = 0.304, 95%CI: 0.104–0.886, P = 0.029), as well as education levels, diabetes duration, cardiovascular disease, serum HbA1c, HDL-C, creatinine, and BDNF, were independent risk factors of MCI in patients with T2DM. This evidence concerns the gene APLN and diabetes mellitus.