Cognitive training to protect immune systems of older caregivers

 描述(由申请者提供)：暴露在慢性应激源下--即长期存在的苛刻生活状况--会加速免疫系统的老化。 被称为免疫衰老，这种免疫衰老的特点是T细胞数量和活性增加，炎症标志物升高。我们的长期目标是为老年人确定适当的治疗靶点，以减轻慢性应激的心理免疫负担。最近的应激适应和神经生物调节模型表明，相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，其中每一个都对应激源的生理和情感适应至关重要。对于老年人来说，衰老和慢性应激相关的神经系统变化可能会损害这些区域的调节，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与应激相关的免疫变化中的作用，这些变化是免疫衰老的信号。我们的中心假设是，认知能力下降将加速暴露在慢性应激源下的老年人的免疫衰老，只要这种下降反映出适应能力--即灵活和适应性地应对环境挑战的能力--的整体下降。我们建议在患有痴呆症的配偶的老年照顾者中测试这一假设，痴呆症患者是压力相关免疫老化的高危人群。我们的目标是通过使用前面展示的认知训练计划来直接探索认知贡献对适应能力和免疫衰老的作用，以提高健康老年人的所谓流动认知能力，特别是处理速度和注意力。重要的是，这种训练还能改善老年人的情绪健康状况。纵向设计将提供对流体认知能力、ANS反应和情绪调节、总体情绪幸福感和免疫标记物(炎性细胞因子和T细胞标记物)的重复评估，以及对中介作用的分析。具体地说，配偶照顾者将被随机分配到从事基于家庭的、计算机化的认知培训，或被分配到不接受培训的控制组。然后，我们将检查在12个月期间发生的认知、心理生理学、情绪和免疫学变化。我们的具体目标是：(1)确定认知训练对照顾者适应能力的认知、自主神经和情绪标记物的影响；(2)确定认知训练对照顾者炎性细胞因子水平和T细胞衰老标记物的影响；(3)确定认知训练对免疫结果影响的认知、自主和情绪相关中介因素。这项拟议的工作有望确定老年人因照料压力而产生的不良情绪健康和免疫衰老的机制。这种识别将使人们能够深入了解新的干预目标，如认知训练，以促进老年人的幸福感。

 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.