These overall findings can be moderated by individual risk factors, which include brain cancer, hormone-related cancers, anti-hormonal therapy, chemotherapy, cranial radiation, genetic predisposition (e.g., APOE, COMT, BDNF), age, frailty and cognitive reserve, depression or post-traumatic distress, sleep, fatigue, and social factors. The gene discussed is APOE; the disease is major depressive disorder.