Precision Aging Network: Closing the Gap Between Cognitive Healthspan andHuman Lifespan

摘要/摘要：总体项目 精密老龄化网络(PAN)的战略愿景是发展基本的科学知识，以 了解目前认知健康寿命和人类寿命之间存在的差异。我们必须 揭示的神经机制，1)解释了在老年时大脑的最佳表现导致健康 认知功能，以及2)大脑功能下降导致与年龄相关的认知的基础 损害(ARCI)、阿尔茨海默病(AD)或阿尔茨海默病相关痴呆(ADRD)。终极的 PAN的目标不仅是为所需的基本知识奠定坚实的科学基础 将认知健康寿命与人类寿命相匹配，但也要利用应用精确度的大数据方法 延长最佳大脑功能的医学概念。为了实现维持最佳认知的目标 在老年时发挥作用，并提高人们在ARCI、AD或ADRD风险水平上的生活质量， 我们坚持认为，将需要在PAN中制定和实施的方法。 尽管“实际年龄”与不断增加的残疾发生率有关，包括慢性病 大脑疾病，如AD和ADRD，确切的机制关系之间的生物年龄和 大脑功能的下降还不得而知。目前患有某种形式痴呆症的人数是 据估计，全球有5000万人，预计每20年翻一番。因为巨大的 70多岁、80多岁和90多岁的人大脑和认知功能的异质性是一个紧迫的挑战 对于科学、医学和医疗保健提供者来说，就是要发现单独有效的干预措施 延迟或阻止ARCI、AD或ADRD。 要理清年龄和认知表现之间的复杂关系，需要一种策略，包括 对非常大的、多样化的、特征良好的和纵向抽样的种群的研究。这将需要 ‘大数据’，也是将收集到的海量信息转化为‘智能数据’的手段 “知识”。这需要截然不同的概念模型。目前，没有一种单一的方法能够充分 确定修改个人老化轨迹以改善个人大脑健康的方法。这个 PAN中提出的方法是为了克服早期方法的障碍。重点是如何 区分年龄、性别、遗传、种族、健康、生活方式选择和 影响大脑驱动因素的环境因素会增加对功能障碍的易感性，以及 这些因素可以增强大脑保护和对功能障碍的抵抗力。 精准医疗的基本原则是“个体化”。这将使强大的 以及对每个人的具体预测，以缩小认知健康寿命与人类之间的差距 寿命。这个概念的根源在于希波克拉底的教义，希波克拉底说过：“更重要的是知道 什么样的人得了什么病，而不是知道一个人得的是什么病。

SUMMARY/ABSTRACT: Overall Project The strategic vision of the Precision Aging Network (PAN) is to develop the essential scientific knowledge to understand the discrepancy that currently exists between cognitive healthspan and human lifespan. We must reveal the neural mechanisms that 1) account for optimal brain performance in old age resulting in healthy cognitive function, and 2) those that underlie decline in brain function leading to age-related cognitive impairment (ARCI), Alzheimer’s disease (AD), or Alzheimer’s disease-related dementias (ADRD). The ultimate goal of the PAN is to develop not only a strong scientific foundation for the essential knowledge needed to match cognitive healthspan with human lifespan, but also to leverage big data approaches that apply precision medicine concepts to prolong optimal brain function. To achieve this goal of sustaining optimal cognitive function in old age, and to extend quality of life for people across levels of risk for ARCI, AD, or ADRD, we maintain that methodologies such as those developed and implemented in the PAN will be required. Although ‘chronological age’ is consistently associated with increasing incidence of disability, including chronic brain disorders such as AD and ADRD, the exact mechanistic relationships between ‘biological age’ and decline in brain function is not known. The number of people now living with some form of dementia is estimated to be 50 million worldwide, which is expected to double every 20 years. Because of the enormous heterogeneity in brain and cognitive function among individuals in their 70s, 80s and 90s, the urgent challenge for science, medicine and healthcare providers is to discover interventions that are individually effective in delaying or preventing ARCI, AD, or ADRD. Untangling the complex relationship between age and cognitive performance requires a strategy that includes the study of very large, diverse, well-characterized and longitudinally sampled populations. This will require ‘big data’ but also the means to translate the massive amounts of information gathered into ‘smart data’ or ‘knowledge’. This demands radically different conceptual models. Currently, no single approach adequately identifies the means to modify personal aging trajectories for improved brain health in individuals. The approach proposed in PAN is designed to overcome obstacles of earlier methods. The focus is on how to distinguish the various combinations of age, sex, genetics, race-ethnicity, health, lifestyle choices and environmental factors that influence brain drivers that increase susceptibility to dysfunction, as well as those factors that increase brain protection and resistance against dysfunction. The fundamental principle of the precision medicine approach is to ’individualize’. This will enable strong and specific predictions for each person to close the gap between cognitive healthspan and human lifespan. The root of this concept is in the teachings of Hippocrates, who said – “It is more important to know what sort of person has a disease than to know what sort of disease a person has.”