Metabolic syndrome is one of the determinants of lifespan in Japan. In order to prevent the acute vascular events, intervention is recommended. However, management of patients with this syndrome increased the number of patients with cognition decline and depressive state. Endocrinological studies with human and experimental animals showed that there is a negative relationship between progression of metabolic syndrome and occurrence of mental disorders. In this review, we summarize our clinical and experimental data, and discuss on the mechanism of the metabolic syndrome prevention of progression of age-related mental disorder.