This paper presents an efficient computer-aided diagnosis (CAD) approach for the automatic detection of Alzheimer’s disease in patients’ T1 MRI scans using the voxel-based morphometry (VBM) analysis of the region of interest (ROI) in the brain. The idea is to generate a normal distribution of feature vectors from ROIs then later use for classification via Bayesian regularized neural network (BR-NN). The first dataset consists of the magnetic resonance imaging (MRI) of 74 Alzheimer’s disease (AD), 42 mild cognitive impairment (MCI), and 74 control normal (CN) from the ADNI1 dataset. The other dataset consists of the MRI of 42 Alzheimer’s disease dementia (ADD), 42 normal controls (NCs), and 39 MCI due to AD (mAD) from our GARD2 database. We aim to create a generalized network to distinguish normal individuals (CN/NC) from dementia patients AD/ADD and MCI/mAD. Our performance relies on our feature extraction process and data smoothing process. Here the key process is to generate a Statistical Parametric Mapping (SPM) t-map image from VBM analysis and obtain the region of interest (ROI) that shows the optimistic result after two-sample t-tests for a smaller value of p < 0.001(AD vs. CN). The result was overwhelming for the distinction between AD/ADD and CN/NC, thus validating our idea for discriminative MRI features. Further, we compared our performance with other recent state-of-the-art methods, and it is comparatively better in many cases. We have experimented with two datasets to validate the process. To validate the network generalization, BR-NN is trained from 70% of the ADNI dataset and tested on 30% of the ADNI, 100% of the GARD dataset, and vice versa. Additionally, we identified the brain anatomical ROIs that may be relatively responsible for brain atrophy during the AD diagnosis.