DESCRIPTION (provided by applicant): Influenza infection results in 41,000 deaths every year in the US and is the seventh leading cause of death. Strikingly, older adults, and especially those at risk for chronic medical disorders, account for approximately 90% of these deaths. Studies comparing influenza vaccine responses of older adults with those of young adults show that immune responses are significantly decreased in older adults. It is estimated that influenza vaccine efficacy is approximately 30-50% in older adults, compared to 70-90% in young-middle aged adults. Compounding this age-related decline in response to vaccination are findings that depression and chronic stress further impair older adults' immune responses to influenza vaccination. Caregiving for a family member with dementia is a robust stressor, and is associated with poor responses to influenza vaccination in older adults, as well as increased levels of proinflammatory biomarkers, which mediate many of the chronic diseases of aging. In this proposal, we consider the immunological consequences of the significant psychological distress experienced by older adult caregivers of family members with dementia. A wide variety of psychosocial interventions can lessen the psychological burden of family or spousal dementia caregiving; Mindfulness Based Stress Reduction (MBSR) in particular has psychological benefit for caregivers, yet its biological effects for these burdened caregivers remain unknown. Here we propose a randomized controlled trial (RCT) of MBSR for older adult caregivers of family dementia patients. Notably, no RCT to-date has done all of what we propose to do: focus on older adult family dementia caregivers who experience significant psychological distress; have as the primary outcome measure adaptive humoral and cellular immune response to influenza vaccine; include surveillance for influenza-like disease during flu season; include evaluation of proinflammatory biomarkers associated with morbidity and mortality in older adults; consider changes in mindfulness and stress as mediators of MBSR's effects on immune function; and include a long-term follow-up of MBSR practice activities. Our aims are to: Aim 1. Identify the effects of MBSR training and practice on adaptive immune responses to influenza vaccination as well as outcomes following influenza infection in stressed older adult family dementia caregivers. Aim 2. Identify the effects of MBSR training and practice on circulating levels of the proinflammatory biomarkers IL-6, tumor necrosis factor (TNF)-α, IL-17 and the acute phase reactant C-reactive protein (CRP), which are elevated in older adults and associated with many chronic diseases of aging. Exploratory Aim 3. Examine relationships among improved adaptive immunity, inflammation and flu outcomes following naturally-acquired influenza infection using a full mediation model. Overall, this research will illuminate whether MBSR can slow the age-related chan...