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Objective To investigate the brain grey matter atrophy in Alzheimer disease (AD) and mild cognitive impairment (MCI), and provide a detective method for exploring the evolution mechanism of AD.Methods By combining voxel based morphometry (VBM) and diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL), we firstly register and segment three T1 structural MRI datasets of 58 normal control (NC), 40 AD patients, 72 MCI patients including 26 progressive MCI (PMCI) patients and 46 stable MCI (SMCI) patients.Then a specific template is built by using DARTEL method.Through deformation fields, the grey matter images are registered to MNI space with preserving the total amount of voxels by applying modulation method.Finally, statistical analysis is made on the processed datasets with two sample t test (P≤0.005, uncorrected).Results Compared to NC, the atrophy regions in AD mainly locate in the bilateral temporal lobe, the bilateral hippocampus and parahippocampal gyrus, the bilateral amygdala,the bilateral insula, the left middle occipital gyrus, the left precuneus, the left posterior cingulate gyrus.The atrophy regions in MCI locate in the bilateral putamen, the left amygdale and the left hippocampus.The atrophy regions in PMCI locate in the left putamen, the left amygdala and the left hippocampus.There is no atrophy region found in SMCI.Compared to MCI, the atrophy regions in AD are the bilateral temporal lobe, the bilateral hippocampus, the bilateral precuneus, the bilateral middle frontal gyrus, the left cingulate gyrus, the left insula, the right amygdala, the right parahippocampal gyrus, the right superior parietal gyrus.There is no atrophy region in MCI compared to AD.Compared to SMCI, the atrophy region in PMCI is in left inferior temporal gyrus, yet there is no atrophy region found in SMCI compared to PMCI.Conclusions VBM-DARTEL based method can achieve a more accurate registration of MRI images and detect subtle volume changes of cerebral grey matter, which is helpful in providing reliable radiology evidence for the early AD diagnosis.