We collected brain MRI of 2,000 healthy Japanese subjects and constructed an MRI database together with their characteristics such as age, sex, present and past disease history and cognitive functions. Volumetric analysis of the brain revealed that gray matter volume linearly decreased with time, while white matter volume remained relatively unchanged during aging. We defined a standard brain for each age group and sex, which is a brain having gray matter volume on the regression line for the gray matter loss with age. This is a first objective criterion for standard brain for his/her age. Then, we performed longitudinal study in the same subjects with 8 years interval. The analyses revealed that there are sex difference in speed and pattern of gray matter loss with aging. Gray matter loss with aging was slower in women that that in men. Voxel based morphometry (VBM) was performed to investigate correlation between regional gray matter volume and characteristics of the subject, such as cerebro-vascular risk factors, scores of cognitive and memory functions, and mental status. These attributes were used as dependent variables, and regional gray matter volume as an independent variable. The correlation analyses revealed that there were negative correlations between gray matter volume and hypertension, lifetime alcohol intake, obesity. To clarify clinical significance of ischemic lesion in the white matter on T2-weighted brain MRI, we developed an algorism for automatic detection of the ischemic lesions. Using this system, we made probabilistic map of the lesion for each subject and the probabilistic maps for age of 40th, 50th,.60th and 70th, by simply averaging the data belonging to the age group. The lesion map revealed that ischemic lesion localized mainly around the ventricle and total lesion volume increased with increasing of age.