Biopsychosocial Mechanisms of Successful Aging

成功衰老的生物心理社会机制

• 批准号: 10367055
• 负责人: Lisa Feldman Barrett
• 金额: $ 81.15万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367055
• 关键词: Adult; Affect; Affective; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer’s disease biomarker; American; Amygdaloid structure; Amyloid; Anatomy; Arousal; Autonomic nervous system; Behavior Therapy; Biological; Biological Markers; Brain; Cardiac Output; Cognition; Cognitive; Cognitive aging; Communication; Development; Elderly; Exercise; Exhibits; Functional disorder; Funding; Goals; Health; Heterogeneity; Impaired cognition; Impairment; Individual; Individual Differences; Intervention; Intervention Studies; Measures; Memory; Modeling; Motivation; Neurobiology; Outcome; Outcome Measure; Outcomes Research; Participant; Pattern; Performance; Persons; Physiological; Physiological Processes; Population; Public Health; Research; Role; Sampling; Structure; Subgroup; Testing; Vascular resistance; Visceral; age related; base; behavior measurement; biobehavior; biopsychosocial; body system; cingulate cortex; cognitive ability; cognitive function; cognitive performance; cognitive task; experience; healthy aging; improved; individual variation; innovation; insight; lifestyle intervention; neural patterning; neuroimaging; neuromechanism; novel strategies; potential biomarker; pre-clinical; predictive marker; preservation; protective factors; psychologic; relating to nervous system; resilience; response; young adult

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.

众所周知，在大多数人中，认知能力随着年龄的增长而下降。随着人口的增长 （到2030年，有20％的美国人将超过65岁），这是一个重大的公共卫生问题。但是，不是 所有老年人都表现出这种衰落模式。我们和其他人证明了有些人似乎 即使在阿尔茨海默氏病（AD）的生物标志物的环境中，也可以抵御与年龄有关的下降 神经病理学变化。了解促进老年人弹性的因素可能指向新的 在所有成年人中实现健康衰老的方法。 在我们最近的衰老研究中，我们在记忆中确定了老年人内的实质性异质性 性能以及大脑解剖和连通性，使得某些年长的参与者（60 - 80年）是 与年轻人无法区分（18-32）。这些非凡的人提供了调查的机会 有助于成功衰老的生物行为机制。 我们的发现表明，成功的衰老者（在内部显示了保存的解剖结构和之间的连通性 多个边缘和旁白结构，可弥补动机，影响和认知）暴露了一个独特的 与典型年龄相比，对挑战任务的神经反应。十足的成功年龄也有所不同 在他们对任务的主观经验中，将任务引起的唤醒评估更加令人愉悦。 总之，这些结果表明，困难期间对唤醒的响应的个体差异 认知任务对衰老的认知结果有意义。 在这里，我们在挑战/威胁连续体（ACT-C）模型中介绍了唤醒，该模型假设 这种唤醒可能对认知有帮助或有害，具体取决于它在大脑和身体中的表达方式 在此提案中，我们将检验ACT-C模型的中心假设，即在 情感的经验及其神经生物学和自主性物理相关性预测认知 衰老的表现。我们建议提高的努力和认知表现将与 倾向于主观体验唤醒的挑战而不是威胁（AIM 1），一种自主教 对以前与挑战解释相关的困难任务的身体反应（即减少 血管抗性，AIM 2）以及一种神经“挑战”模式，涉及中性抑制活性增加和 网络之间的通信（AIM 3）。至关重要的是，我们预测这些动机，生理和 即使在具有临床前AD证据的个体中，神经因素也会与改善性能有关。 如果成功的话，这项研究将提供急需影响的生物学机制的见解 和动机支持认知衰老。这项研究的结果可能会指向神经和 预测成功衰老的物理生物标志物，可用于评估干预措施以促进 成功的衰老，包括具有临床前广告的生物标志物证据的人。