A program of research is proposed to systematically examine the effects of an interactions among stress, endocrine function, and social support on health and aging. Physiological stress and the effects of psychosocial support on physiological stress will be assessed by measurements of the hypothalamic-pituitary-adrenal axis (HPA) in aging adults with differing diseases and health program: breast cancer, heart disease, neurocognitive decline, and psychological distress. This Program Project includes collaborating investigators from the Department of Psychiatry and Behavioral Sciences at Stanford with substantial expertise in stress assessments and management, psychoneuroendocrinology, and aging. In addition, advice has been provided and will be solicited throughout from a distinguished external Scientific Advisory Board with knowledge in these areas. Recent data obtained here at Stanford provide the platform for this Program Project. The findings show clearly that abnormal diurinal variation of cortisol predicts shorter subsequent survival time in patients with metastatic breast cancer. We propose to determine whether this finding pertains generally to the above health outcomes in aging, and if so whether new strategies can provide more effective therapeutic interventions. In this Program Project we propose hypotheses concerning how various risk factors interact to affect HPA function and health outcomes in aging, i.e. which variables act as mediators of moderators of stress response. Specifically, we propose four projects, two of which will investigate these relationships within a disease model and two others examining cognitive and psychological outcomes in older adults: 1) Dr. Spiegel will examine tonic and stress-induced activation of the HPA and immune systems in metastatic breast cancer patients in relation to disease progression; 2) Dr. Taylor will study the effect of cognitive-behavioral treatment for depression on HPA and symptomedullary activity and cardiovascular risk; 3) Dr. O'Hara will study stress, HPA activity and hippocampal volume using MRI in relation to cognitive decline; and 4) Dr. Gallagher-Thompson will evaluate effects of stress-management treatments for caregivers of elders with dementia on HPA function and distress. Using this multi-pronged approach, the Program would provide definitive evidence regarding the potential role of HPA function in mediating the effects of stress and social support on disease progression in diverse disease states that are prevalent among the aged.