By multivariate logistic regression analyses of the data received from both current and our previous cohorts, we observed that an elevated ratio of Aβ1-42 to Aβ1-40 was an independent risk factor for cognitive decline in T2DM patients; furthermore, addition of the elevated Aβ1-42/Aβ1-40 into our previously established model (i.e., upregulated platelet GSK-3β activity, ApoE ε4 genotype, olfactory dysfunction, and aging) remarkably increased the diagnostic efficiency of MCI from T2DM patients in both training and validation cohorts. The gene discussed is APOE; the disease is type 2 diabetes mellitus.