Objective To investigate the methylation status of the promoter region of androgen receptor (AR) gene and homocysteine (Hcy) level in patients with vascular cognitive impairment (VCI), as well as the association of VCI with a high methylation level of the promoter region of AR gene and Hcy level.Methods A case-control study was performed. A total of 46 VCI patients in the chronic period of stroke were enrolled as case group, and 92 healthy persons matched for age were enrolled as control group. Methylation-specific PCR and RT-PCR were used to determine the methylation status of the CpG islands in the promoter region of AR gene and measure the mRNA expression of AR gene, and enzymic transformation was used to measure the Hcy level.Results There was a significant difference in methylation rate between the case group and the control group (71.74% vs 19.57%, P<0.05). The mRNA expression of AR gene in the case group was 5.24 times lower than that in the control group, and there was a significant difference in the loss rate of mRNA expression of AR gene between the two groups (P<0.05). The case group had a significantly higher Hcy level than the control group (14.73±5.31 vs 7.12±4.19, P<0.05). The methylation level of the promoter region of AR gene was significantly correlated with Hcy level (r=0.534); in the case group, the methylation level increased with the increasing Hcy level.Conclusions A high methylation level of the promoter region of AR gene is associated with the pathogenesis of VCI, and a high Hcy level is associated with the high methylation level of the promoter region of AR gene.