NR3C1 and Cognitive impairment: Indeed, maintenance of low glucocorticoid level throughout life, either via neonatal ‘programming’ of GR and MR in hippocampus which afford tighter HPA axis control, by antidepressant drugs which up-regulate GR and MR in the hippocampus and other feedback sites in adulthood to similar effect, or by adrenalectomy with low-dose glucocorticoid replacement in mid-life, prevent the emergence of cognitive deficits with age [140,166,314].