Project Summary/ Abstract Caregiving for a spouse with Alzheimer?s Disease (AD) is one of the most stressful experiences a person can encounter. Among married couples when one member of the dyad has AD, the disease is often described as a relational illness because every aspect of the disease necessarily involves the spouse. Poor quality of life (QOL) and caregiver burden characterize a significant proportion of AD spousal caregivers. AD spousal caregivers also experience living bereavement as they experience profound feeling of grief analogous to what one experiences when a spouse dies. The chronic stress of spousal AD caregiving magnifies age- related changes in proinflammatory cytokines, an important predictor of morbidity and mortality. Mechanistically, chronic stress promotes desensitization of glucocorticoid receptors promoting glucocorticoid receptor resistance (GCR), which allows for elevated inflammation. Of course, not all AD spousal caregivers are at the same level of risk. However, research attempting to identify which AD spousal caregivers are at greatest risk is remarkably sparse. Out of the 173 studies examining the biological markers of physical health in relation to AD spousal caregivers, there is no work, to our knowledge, that examines how relationship and/or personality characteristics affect biological markers of physical health. Determining stable individual difference characteristics is critical to developing evidence-based treatments. Attachment theory is a useful framework for understanding individual differences in close relationships as well as how people cope with stressful life events. There are two patterns of attachment insecurity: attachment anxiety and attachment avoidance. People with high attachment anxiety use hyperactivating emotional coping strategies that accentuate the stress response. People with high attachment avoidance are uncomfortable depending on others and use deactivating coping strategies in an attempt to inhibit stress. This investigatory team demonstrated that compared with bereaved adults with low attachment anxiety, recently bereaved adults with higher attachment anxiety experienced more grief, more depressive symptoms, and elevated inflammation. Those who reported more grief had elevated levels of inflammation compared with those who reported less grief. Likewise, those who reported poorer QOL had higher levels of inflammation than those who reported better QOL. Our pilot work in AD spousal caregivers echoes these findings. We have also demonstrated that the association between attachment avoidance and health outcomes is moderated by high heart rate variability (HF-HRV), an important marker of aging, and emotion regulation (HF-HRV). We build upon our findings in bereaved adults to advance our understanding of which AD spousal caregivers are most vulnerable to the deleterious physical health effects of spousal dementia caregiving as they navigate the experience of living bereavement, while coping with the burden of caregiving and trying to maintain QOL. As an exploratory aim, we will examine how these individual differences in attachment orientation affect both members of the marital relationship.