Cognitive training to protect immune systems of older caregivers

 描述（由申请人提供）：暴露于慢性应激源-即长期持续的苛刻生活环境-加速免疫系统的老化。 这种免疫老化被称为免疫衰老，其特征是T细胞数量和活性的不断变化以及炎症标志物的升高。我们的长期目标是为老年人确定适当的治疗目标，以减少慢性应激的心理免疫负担。最近的压力适应和神经生物学调节模型表明，类似的神经结构和网络支持认知、自主神经系统（ANS）和情绪调节，其中每一个对于对压力源的生理和情绪适应都很重要。对于老年人，衰老和慢性应激相关的神经系统变化的组合可能会损害这些领域的调节，从而降低应激适应能力，增加对加速免疫衰老的易感性。我们目前的目标是研究认知功能在适应能力和应激相关的免疫改变中的作用，这些免疫改变是免疫衰老的信号。我们的核心假设是，认知能力下降将加速暴露于慢性压力源的老年人的免疫衰老，因为这种下降反映了适应能力的整体下降-即灵活和适应环境挑战的能力。我们建议在老年痴呆症配偶的老年照顾者中测试这一假设，这是一个与压力相关的免疫衰老高风险人群。我们的目标是通过使用先前显示的认知训练计划来直接探索认知对适应能力和免疫衰老的作用，以改善健康老年人的所谓流体认知能力，特别是处理速度和注意力。重要的是，这种训练也导致老年人更好的情绪健康。纵向设计将提供对流体认知能力、ANS反应和情绪调节、一般情绪健康和免疫标记物（炎性细胞因子和T细胞标记物）的重复评估，以及对中介效应的分析。具体来说，配偶照顾者将被随机分配到从事以家庭为基础的，计算机化的认知训练，或一个没有培训的对照组。然后，我们将研究在12个月期间发生的认知，心理生理，情绪和免疫变化。我们的具体目标是：（1）确定认知训练对照顾者的适应能力的认知、自主和情绪标记物的影响（2）确定认知训练对照顾者的炎性细胞因子水平和T细胞衰老标记物的影响，以及（3）确定认知训练对免疫结果影响的认知、自主和情绪相关介质。本文提出的工作预计将确定老年人的不良情绪健康和免疫衰老所产生的压力。这一确定将为新的干预目标提供洞察力，如认知训练，以促进老年人的福祉。

 DESCRIPTION (provided by applicant): Exposure to chronic stressors - that is, demanding life situations that persist for long periods of time - accelerates the aging of the immune system. Termed immunosenescence, this immune aging is marked by increasingly altered T cell numbers and activity and elevated markers of inflammation. Our long-term objective is to identify appropriate therapeutic targets for older adults to reduce the psycho-immunological burden of chronic stress. Recent models of stress adaptation and neurobiological regulation suggest that similar neural structures and networks support cognition, the autonomic nervous system (ANS) and emotion regulation, each of which are important for physiological and emotional adaptation to stressors. For older adults, a combination of aging- and chronic stress-related neurological changes may compromise the regulation of these domains, thereby reducing stress adaptation capacity and increasing susceptibility to accelerated immunosenescence. Our current objective is to examine the role of cognitive function in adaptive capacity and stress-related immune alterations that signal immunosenescence. Our central hypothesis is that cognitive decline will accelerate immunosenescence in older adults exposed to chronic stressors, insofar as such decline reflects an overall reduction in adaptive capacity - that is, the capacity to respond flexibly and adaptively to environmental challenges. We propose to test this hypothesis in older caregivers of a spouse with dementia, a population at high risk for stress-associated immune aging. We aim to directly probe the role of cognitive contributions to adaptive capacity and immunosenescence by using a cognitive training program shown previously to improve so-called fluid cognitive abilities, particular processing speed and attention, in healthy older adults. Importantly, this training also led to better emotional well-beng in older adults. A longitudinal design will afford repeated assessments of fluid cognitive abilitie, ANS responses and emotion regulation, general emotional well-being and immune markers (inflammatory cytokines and T-cell markers), and analyses of mediational effects. Specifically, spousal caregivers will be randomly assigned to engage in home-based, computerized cognitive training, or to a no-training control group. We will then examine the ensuing cognitive, psychophysiological, emotional and immunological changes that occur over a 12-month period. Our specific aims are to: (1) identify effects of cognitive training on caregivers' cognitive, autonomic and emotion markers of adaptive capacity (2) identify effects of cognitive training on caregivers' inflammatory cytokine levels and markers of T cell senescence, and (3) determine cognitive, autonomic, and emotion-related mediators of cognitive training effects on immune outcomes. The work proposed here is expected to identify mechanisms involved in older adults' poor emotional well-being and immunosenescence arising from caregiving stress. This identification will afford insight into new intervention targets, such as cognitive training, to promote older adults' well-being.