Glucocorticoid and mineralocorticoid receptor signals are important for memory formation, salt cravings, sympathetic tone and hypothalamic–pituitary–adrenal (HPA) axis control in the brain. Exacerbations of glucocorticoid and mineralocorticoid receptor signaling cause atherosclerosis, cognitive dysfunction, and depression. Mineralocorticoid activity is modulated by oxidative stress, and chronic stress desensitize further nongenomic mineralocorticoid receptor action. In patients with chronic diseases such as diabetes and hypertension, oxidative stress in the brain is increased, which alters the balance of the HPA axis, resulting in an elevated risk of dementia. Therefore, oxidative stress and mineralocorticoid receptor blockade are possible therapeutic targets for cognitive dysfunction.