Aims In order to confirm the utility of the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) in assessing the atrophy of the entorhinal cortex, we investigated whether there were correlations between VSRAD and the scores of neuropsychological tests in the patients with Alzheimer's disease (AD) and mild cognitive impairment. Methods Thirty patients, including 18 AD and 12 mild cognitive impairment patients, were included in this study. VSRAD was performed to assess the atrophy of the entorhinal cortex. The patients were carefully screened with the neuropsychological tests, including Wechsler Adult Intelligence Scale-III (WAIS-III), the Wechsler Memory Scale-Revised, the Alzheimer's Disease Assessment Scale-Cognitive Part (ADAS-cog) and the revised version of Hasegawa's Dementia Scale. Results All patients showed atrophy with different degrees in the entorhinal cortex except one case. Z-scores had significant positive correlation with ADAS-cog, and negative correlation with Information subset of WAIS-III (respectively, P?=?0.0129 and P?=?0.0294). The revised version of Hasegawa's Dementia Scale and the Similarities subsets of the WAIS-III had a tendency of negatively correlating with Z-scores of VSRAD (respectively, P?=?0.0532 and P?=?0.0635). The Delayed Visual Reproduction subset of the Wechsler Memory Scale-Revised was also found to have a weak negative correlation with Z-scores (P?=?0.0609). Conclusions Z-scores of VSRAD were revealed to have a close relation with many neuropsychological tests, especially ADAS-cog and the Information subset of WAIS-III. The results meant that VSRAD was a useful indictor of early diagnosis of AD, closely correlating with the changes of cognitive functions and the progression of the disease.