After adjusting for APOE ε4 mutations, there was no statistically significant difference in the risk association between DM and AD (HR = 1.07, 95% CI (0.97-1.19), <i>P</i> = 0.177), whereas without adjustment for APOE ε4 mutation, DM was associated with an increased AD risk (HR = 1.42, 95% CI (1.23-1.64), <i>P</i> < 0.00001).<h4>Conclusion</h4>This meta-analysis provides compelling evidence that DM is an independent risk factor for AD, offering important implications for clinical practice and future research. This evidence concerns the gene APOE and diabetes mellitus.