Resilience and brain health of older adults during the COVID-19 pandemic

摘要： 锻炼和正念被认为是有效的减压干预措施，但到目前为止，研究已经 当个人实时应对主要压力源时，无法评估他们的好处。这个 新冠肺炎大流行是压力--尤其是社交压力--有害影响的自然实验 与世隔绝(社交孤立和孤独)，这是一种与 流行病--对美国老年人的认知和情绪健康以及阿尔茨海默病(AD)风险的影响。这 该项目将阐明锻炼和正念是否可以减轻大流行压力对 认知功能和晚年情绪健康，包括阿尔茨海默病风险的神经生物学测量。 我们将利用一项独特的资源：由美国国立卫生研究院资助的试验，“基于正念的压力减轻和锻炼” 与年龄相关的认知功能下降“(MEDEX)。通过利用Medex并跟踪这些参与者，谁 在大流行期间继续远程参加每月一次的随机情况助推会，我们 将在7.5年期间进行一系列重复的临床、认知、分子和神经成像测量 大流行前、大流行期间和大流行后时期。我们可以检查干预效果，以及个别因素。 例如韧性，对长期结果的影响。在该项目的其他创新方面，我们将分析 对两种新的外周生物标志物：衰老相关分泌表型(SASP)的影响 测量生物衰老的机制，以及测量AD风险的血浆淀粉样蛋白Aβ42和Aβ40。 在拟议的项目中，(1)在大流行期间，我们将使用新的方法，如生态瞬时 评估(EMA)客观地描述社会孤立(例如，社会联系的数量)和 主观上(如孤独)及其衰老的生物学机制(如SASP和血浆中的升高 淀粉样蛋白)；(2)大流行后，我们将评估下游对认知功能、情绪健康、 以及大脑健康，包括AD风险，使用神经心理评估、EMA和神经成像。 结果包括(目标1)认知表现和情绪幸福感的变化，以及 情绪幸福感通过积极和消极的情绪和睡眠质量来衡量；生物衰老的增加 在大流行后阶段，AΒ42/40比值降低，表明患AD的风险更高；海马区萎缩 前额叶体积(结构磁共振成像)和全局功能连接性降低(静息状态功能磁共振成像)。 这些效果的修饰者(目标2)包括锻炼和正念；心理韧性；新冠肺炎 暴露；医疗疾病；以及APOE基因。认知、情绪和大脑健康的机制 变化(目标3)包括大流行期间的淀粉样蛋白(Aβ40和Aβ42)、SASP、DNA甲基化和皮质醇。 这个项目将增进我们对社会孤立和其他压力源对老年人的影响的了解， 包括这些应激源产生有害的认知、情绪和大脑健康的机制 随着时间的推移而变化，以及锻炼和专注是否具有持久的保护效果。

Abstract: Exercise and mindfulness are believed to be effective stress reduction interventions, but research to date has not been able to assess their benefits while individuals are coping with a major stressor in real time. The COVID-19 pandemic is an unwanted natural experiment in the deleterious effects of stress – especially social isolation (social disconnectedness and loneliness), a stressor particularly strongly associated with the pandemic - on older Americans’ cognitive and emotional health and risk for Alzheimer’s Disease (AD). This project will elucidate whether exercise and mindfulness can mitigate the effects of pandemic stress on cognitive function and emotional health in later life, including neurobiological measures of risk for AD. We will leverage a unique resource: the NIH-funded trial, “Mindfulness-Based Stress Reduction and Exercise for Age-Related Cognitive Decline” (MEDEX). By leveraging MEDEX and following these participants, who continue to attend monthly booster sessions of their randomized condition remotely during the pandemic, we will have repeated sets of clinical, cognitive, molecular, and neuroimaging measures covering 7.5 years during the pre-, during-, and post-pandemic period. We can examine intervention effects, as well as individual factors such as resilience, on long-term outcomes. Among other innovative aspects of the project, we will analyze effects on two novel peripheral biomarkers: Senescence-Associated Secretory Phenotype (SASP), which measures mechanisms of biological aging, and plasma amyloid Aβ42 and Aβ40, which measure AD risk. In the proposed project, (1) during the pandemic, we will use novel methods such as Ecological Momentary Assessment (EMA) to characterize social isolation both objectively (e.g., number of social contacts) and subjectively (e.g., loneliness), and its biological mechanisms on aging (such as elevations in SASP and plasma amyloid); (2) post-pandemic, we will assess downstream effects on cognitive function, emotional well-being, and brain health, including AD risk, using neuropsychological assessments, EMA, and neuroimaging. Outcomes include (Aim 1) changes in cognitive performance and emotional well-being, and decline in emotional well-being measured by positive and negative affect and sleep quality; increases in biological aging and decreasing AΒ42/40 ratio in the post-pandemic phase, indicating higher risk of AD; atrophy in hippocampal and prefrontal volume (structural MRI) and reduced global functional connectivity (resting-state fMRI). Modifiers of these effects (Aim 2) include exercise and mindfulness; psychological resilience; COVID-19 exposure; medical morbidities; and APOE genotype. Mechanisms of cognitive, emotional, and brain health changes (Aim 3) include amyloid (Aβ40 and Aβ42), SASP, DNA methylation, and cortisol during the pandemic. This project will advance our knowledge of the impact of social isolation and other stressors on older adults, including mechanisms by which these stressors produce deleterious cognitive, emotional, and brain health changes over time, and whether exercise and mindfulness have durable protective effects.