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 (到2030年，20%的美国人将超过65岁)，这是一个重大的公共卫生问题。然而，不是 所有的老年人都表现出这种下降的模式。我们和其他人已经证明，一些人似乎 即使在阿尔茨海默病(AD)的生物标记物设置中，也要对与年龄相关的下降保持弹性 神经病理改变。了解促进老年人适应能力的因素可能会指出新的 在所有成年人中实现健康老龄化的方法。 在我们最近关于衰老的研究中，我们发现老年人在记忆中存在显著的异质性 表现以及大脑解剖和连通性，因此一些年龄较大的参与者(60-80岁)是 和年轻人(18-32岁)没什么区别。这些杰出的人物提供了调查的机会 有助于成功衰老的生物行为机制。 我们的发现表明，成功的老年人(他们显示出保存完好的内部解剖结构和相互之间的联系 有助于动机、情感和认知的多个边缘和边缘旁结构)表现出明显的 与典型的老年人相比，对挑战性任务的神经反应。关键是，成功的老年人也有所不同。 在他们对任务的主观体验中，他们认为任务引起的唤醒明显更令人愉快。 综上所述，这些结果表明，在困难时期，个体对唤醒增加的反应存在差异 认知任务对衰老过程中的认知结果有重要影响。 在这里，我们介绍沿挑战/威胁连续体(ACT-C)模型的唤醒，该模型假设 这种兴奋可能对认知有益，也可能有害，这取决于它在大脑和身体中的表达方式。 在这个提案中，我们将检验ACT-C模型的中心假设，即个体在 情感体验及其神经生物学和自主生理关联预测认知 在衰老中的表现。我们提出，更多的努力和认知表现将与 主观上更多地将觉醒体验为挑战而不是威胁的倾向(目标1)，一种自主神经 对以前与挑战解释相关的困难任务的生理反应(即降低 血管阻力，目标2)，以及涉及扣带中活动增加和 网络间通信(目标3)。至关重要的是，我们预测，这些激励、生理和 即使在有临床前AD证据的个体中，神经因素也将与表现的改善相关。 这项研究，如果成功，将提供对影响的生物学机制的迫切需要的洞察力 动机支持认知老化。这项研究的结果可能为神经和 预测成功衰老的生理生物标志物，可用于评估促进衰老的干预措施 成功的衰老，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.