〔Abstract〕 Objective To investigate the differences in gray matter volume(GMV) changes of male and female patients with Alzheimer′s disease(AD) and the potential correlation with cognitive impairment. Methods Eighty-eight patients with AD(37 males and 51 females), 84 patients with amnestic mild cognitive impairment(aMCI, 40 males and 44 females) and 79 healthy controls(HC, 34 males and 45 females) were included. High-resolution 3-dimensional T1 structure images were obtained from each participant. The optimized voxel-based morphological measurement(VBM) method and two-way ANOVA analysis were conducted to investigate differential brain regions with interaction between groups and sexes, which were then chosen as regions of interest(ROI) to extract GMV by the REST software for correlation analysis with the Mini-mental State Examination(MMSE) scores. Results The right temporal pole, right orbital inferior frontal gyrus, right middle temporal gyrus, bilateral anterior cingulate cortex and right middle cingulate cortex were brain regions with interaction between sexes and groups of AD, aMCI and HC(P<0.05,FWEcorrected at cluster level). In HC and aMCI groups, the GMV of females in the aforementioned areas was similar to or slightly larger than that of the males, while in the AD group, it bacame significantly smaller than that of males. For correlation analysis, the aMCI and AD patients were combined and then dimidiated into two groups by sex, MMSE scores of the female patient group positively correlated with GMV of the aforementioned five brain regions(P<0.05), MMSE scores of male patient group were positively correlated with GMV of the right middle temporal gyrus(r=0.265,P=0.020). The aMCI and AD patients were separated and then dimidiated into two groups by sex, MMSE scores positively correlated with the GMV from the right middle temporal gyrus in both the female AD group and male aMCI group(r=0.327,P=0.019 andr=0.419,P=0.007). Conclusion There is a difference between the sexes in terms of gray matter atrophy while AD progresses. In particular, some brain regions atrophy more severely in female patients. The different gray matter atrophy patterns in males and females may lead to differences in cognitive decline during the AD disease process.