Project Summary/Abstract Many studies have shown that providing care for a spouse with dementia can be quite stressful, leading to a heightened risk for depression, multiple negative health outcomes, frailty, and early mortality. Stress- and depression-related immune system alterations are seen as a key pathway to poorer health in caregivers. However, the health impacts of caregiver stress have been questioned in recent years, based on newer evidence that caregiving may benefit health and extend lifespan. Furthermore, even though caregivers have typically had poorer immune function than noncaregiving controls, the clinical significance of these differences has been questioned. These discrepant findings reflect both methodological and conceptual issues that this project will address. Three molecular aging biomarkers (telomere length, p16INK4a expression, and epigenetic age) have each been associated with multiple diseases and disorders. Their combined use will provide an innovative way to quantify the long-term health risks of caregiving, allowing us to ask novel questions: Does caregiving accelerate aging? Can caregiving-related distress propel molecular aging and shorten health span (the length of time that a person is healthy—not just alive)? We will also assess three stress-sensitive pathways relevant to molecular aging: inflammation, intestinal permeability, and cytomegalovirus serostatus and reactivation. Drawing on behavioral, immunological, and molecular aging research, this transdisciplinary study will assess concurrent and prospective relationships related to key caregiving risk-related dimensions (gender, social relationships, caregiving intensity/burden, and benefit finding), and these aging biomarkers. Spousal dementia caregivers and sociodemographically-comparable married noncaregivers will be evaluated at study intake and then again one and two years later. This design will provide longitudinal data to assess changes in caregiving, depression, key risk behaviors, aging biomarkers, and the stress-sensitive pathways related to molecular aging. We have three specific aims: 1) To characterize the concurrent and prospective differences between caregivers and noncaregivers on the molecular aging biomarkers, inflammation, and mood. 2) To assess the relationships among the molecular aging biomarkers. 3) This exploratory aim addresses the relative contributions of key risk-related dimensions to depression, accelerated increases in aging biomarkers, and inflammation. This proposal describes a distinctly novel methodology that will provide a way to test innovative and original hypotheses about the ways that spousal dementia caregiving impacts lifespan and health span. The interactions between behavior and molecular aging represent an important new frontier for understanding how caregiving (and other chronic stressors) can accelerate or slow aging. This cutting edge research will help illuminate the mechanisms through which caregiving and depression influence health and longevity.

Project Narrative This study addresses two key questions: Does the chronic stress of dementia spousal caregiving accelerate molecular aging? Can caregiving-related distress propel molecular aging and shorten health span (the length of time that a person is healthy—not just alive)? This project will provide insight into the pathways through which caregiving can produce substantial health risks, and it will also explore possible paths to caregiving’s potential health benefits.