In this study, we assessed the global changes of leukocyte DNA methylation in MCI- and AD-affected Chinese patients compared to that of cognitively healthy controls and reported multiple potential DNA methylation-based signatures associated with cognitive decline and AD, including CpG positions harbored in RHOJ, PARK2, FLNC, ANKH, and AFAP1 genes. This evidence concerns the gene AFAP1 and Alzheimer disease.