Biopsychosocial Mechanisms of Successful Aging

众所周知，在大多数人中，认知能力随着年龄的增长而下降。随着老年人口的增长 (20到2030年，美国人将超过65岁），这是一个重大的公共卫生问题。但并非 所有老年人都表现出这种衰退模式。我们和其他人已经证明，有些人似乎 即使在阿尔茨海默病（AD）生物标志物的背景下，也能适应与年龄相关的衰退 神经病理改变了解促进老年人恢复力的因素可以指出新的 在所有成年人中实现健康老龄化的方法。 在我们最近对衰老的研究中，我们发现老年人的记忆存在很大的异质性， 性能以及大脑解剖结构和连接性，例如一些老年参与者（60-80岁）是 与年轻人（18-32岁）没有区别。这些杰出的个体提供了一个研究 有助于成功衰老的生物行为机制。 我们的研究结果表明，成功的老年人（谁表现出保存内部解剖和连接之间 多个边缘系统和边缘系统结构，有助于动机，影响和认知）表现出明显的 神经反应的挑战性任务相比，典型的老年人。重要的是，成功的老年人 在他们对任务的主观体验中，将任务引起的唤醒评定为明显更愉快。 总之，这些结果表明，在困难的过程中，个体对增强唤醒的反应存在差异。 认知任务对衰老的认知结果有意义的贡献。 在这里，我们介绍了唤醒沿着挑战/威胁连续体（ACT-C）模型，该模型假设 唤醒对认知是有益的还是有害的，这取决于它在大脑和身体中的表达方式。 在这个建议中，我们将测试ACT-C模型的中心假设，即个体差异， 情感体验及其神经生物学和自主生理学相关性预测认知能力 老化的表现。我们认为，增加努力和认知表现将与 倾向于主观体验唤醒更多的挑战，而不是威胁（目标1），自主神经 对先前与挑战解释相关的困难任务的生理反应（即， 血管阻力，目标2），以及涉及中扣带回活动增加的神经“挑战”模式， 网络之间的通信（目标3）。至关重要的是，我们预测，这些动机，生理， 神经因素将与改善的表现相关，甚至在具有临床前AD证据的个体中。 这项研究，如果成功，将提供急需的洞察力的生物机制，影响 和动机支持认知老化。这项研究的结果可以为神经和 预测成功衰老的生理生物标志物，可用于评估干预措施， 成功老化，包括具有临床前AD生物标志物证据的人。

It is well-known that in most people, cognitive abilities decline with age. With the elderly population growing (20% of Americans will be over 65 by 2030), this represents a significant public health concern. However, not all older adults show this pattern of decline. We and others have demonstrated that some individuals seem to be resilient to age-related decline, even in the setting of biomarkers of Alzheimer’s disease (AD) neuropathologic changes. Understanding the factors that promote resilience in older adults could point to new approaches to achieve healthy aging in all adults. In our recent studies of aging, we identified substantial heterogeneity within older adults in memory performance and both brain anatomy and connectivity, such that some older participants (60-80 yrs.) were indistinguishable from young adults (18-32). These remarkable individuals offer the opportunity to investigate the biobehavioral mechanisms that contribute to successful aging. Our findings indicated that successful agers (who showed preserved anatomy within and connectivity between multiple limbic and paralimbic structures that subserve motivation, affect, and cognition) exhibited a distinct neural response to challenging tasks when compared to typical agers. Crucially, successful agers also differed in their subjective experience of the task, rating the arousal caused by the task as significantly more pleasant. Together, these results suggest that individual differences in the response to increasing arousal during difficult cognitive tasks contribute meaningfully to cognitive outcomes in aging. Here, we introduce the Arousal along the Challenge/Threat Continuum (ACT-C) model, which hypothesizes that arousal can be helpful or harmful to cognition, depending on how it is expressed in the brain and the body In this proposal, we will test the central hypothesis of the ACT-C model, that individual differences in the experience of affect, and its neurobiological and autonomic physiological correlates predicts cognitive performance in aging. We propose that increased effort and cognitive performance will be associated with a tendency to subjectively experience arousal more as challenge than as threat (Aim 1), an autonomic physiological response to difficult tasks previously associated with a challenge interpretation (i.e. decreased vascular resistance, Aim 2), and a neural ‘challenge’ pattern involving increased mid-cingulate activity and communication between networks (Aim 3). Crucially, we predict that these motivational, physiological, and neural factors will be associated with improved performance even in individuals with evidence of preclinical AD. This research, if successful, will provide much-needed insight into the biological mechanisms by which affect and motivation support cognitive aging. The outcomes of this research could point the way to neural and physiological biomarkers predicting successful aging, which could be used to evaluate interventions to promote successful aging, including in people with biomarker evidence of Preclinical AD.