Proposal Summary/Abstract Caregiving for a spouse with Alzheimer’s disease and related dementias (ADRD) is a severe, chronic stressor. The stress associated with ADRD spousal caregiving can be harmful to physical and cognitive health and may partially explain why ADRD spousal caregivers are at heightened risk for accelerated aging and chronic diseases of older adulthood, including ADRD1,2. Chronic stress can promote an overactive proinflammatory state and impair mitochondrial function, processes which are both associated with cognitive impairment3,4. However, not all ADRD spousal caregivers experience harmful effects of caregiving stress on their health5. The ability to effectively regulate emotions may help explain individual differences in health outcomes, as emotion regulation can impact physical and mental health. The process model of emotion regulation proposed by James Gross states that a person may engage in regulatory strategies during the experience of a stressor to change or modify the resulting emotion6–8. Two commonly-used strategies are expressive suppression, which is an effortful inhibition of the outward expression of emotions, and cognitive reappraisal, which involves reevaluating the meaning of an emotionally evocative situation6. The tendency to use expressive suppression is associated with higher perceived stress, inflammatory dysregulation, and poor health outcomes, while the tendency to use cognitive reappraisal is linked with lower perceived stress and may protect against adverse effects of an overactive stress response9,10. As caregiving for a spouse with ADRD is an extreme stressor, the use of expressive suppression may be harmful to the caregiver's health long term, while cognitive reappraisal could protect against poor health outcomes. Although research has explored emotion regulation in spousal caregivers, very few studies have examined biological and cognitive markers of health in relation to emotion regulation in this population. This study aims to test the hypothesis that these emotion regulation strategies are associated with cognitive function, inflammation, and mitochondrial function in ADRD spousal caregivers. Specific Aims: (1) To examine the relationships between emotion regulation, inflammation, mitochondrial function, and cognitive function. (2) To assess the relationship between proinflammatory cytokines, mitochondrial function, and cognitive function. (3 - Exploratory) To explore psychological, molecular, and cellular mechanisms of the association between emotion regulation tendencies and cognitive function. This research could provide a better understanding about the role of emotion regulation strategies in physiological and cognitive health in ADRD spousal caregivers. Results could broaden knowledge about the mechanisms that underlie differences in health outcomes among ADRD spousal caregivers and could yield important clinical implications for identifying individuals at risk and tailoring interventions...