Spousal Dementia Caregivers: Risk for Accelerated Aging

项目摘要/摘要 许多研究表明，照顾患有痴呆症的配偶可能会非常有压力，导致 导致抑郁、多种负面健康后果、虚弱和早期死亡的风险增加。压力- 与抑郁症相关的免疫系统改变被视为导致健康状况变差的关键途径 照顾者。然而，近年来，照顾者压力对健康的影响受到了质疑，基于 最新的证据表明，照料可能有益于健康并延长寿命。此外，即使 照顾者的免疫功能通常比非照顾者的对照组差，这一临床意义 这些差异中的任何一个都受到了质疑。这些不一致的发现既反映了方法上的，也反映了 这个项目将解决的概念性问题。 三个分子老化生物标记物(端粒长度、p16INK4a表达和表观遗传年龄)各有 与多种疾病和失调症有关。它们的结合使用将提供一种创新的方式 量化护理的长期健康风险，使我们能够提出新的问题：护理是否 加速衰老？照看相关的痛苦是否会推动分子衰老和缩短健康寿命( 一个人健康的时间长度--而不仅仅是活着的时间)？我们还将评估三个应激敏感途径 与分子老化有关：炎症、肠道通透性、巨细胞病毒血清和 重新激活。利用行为学、免疫学和分子衰老研究，这一跨学科 研究将评估与关键护理风险相关维度相关的当前关系和预期关系 (性别、社会关系、照顾强度/负担和利益发现)，以及这些老化的生物标志物。 配偶痴呆症照顾者和社会人口学上可比的已婚非照顾者将是 在研究开始时进行评估，然后在一年和两年后再次进行评估。该设计将提供纵向数据 评估照顾、抑郁、关键危险行为、衰老生物标记物和压力敏感性的变化 与分子衰老有关的途径。我们有三个具体目标：1)描述并发和 照顾者和非照顾者在分子衰老生物标志物上的前瞻性差异， 发炎，还有情绪。2)评估分子衰老生物标志物之间的关系。3)这个 探索性目标是解决关键风险相关维度对抑郁的相对贡献， 老化生物标志物和炎症的加速增加。 这项提案描述了一种全新的方法，它将提供一种测试创新和 关于配偶痴呆症护理影响寿命和健康跨度的原创性假设。这个 行为和分子衰老之间的相互作用代表着理解的一个重要新前沿 照顾(和其他慢性压力)如何加速或延缓衰老。这项尖端研究将 帮助阐明照料和抑郁影响健康和长寿的机制。

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.