EFFECTS OF VULNERABILITY AND RESILIENCY ON BRAIN HEALTH DURING THE MID-TO-LATE-LIFE TRANSITION

项目2的摘要 阿尔茨海默病(AD)或AD相关痴呆(ADRD)的有效疾病修正疗法 强调迫切需要确定大脑健康保护因素，以降低脑部疾病的风险 认知衰退、阿尔茨海默病和ADRD。影响可修改风险因素影响的关键时刻是 从中年过渡到晚年(50到80岁)。研究还表明，炎症在 神经退化和扰乱脑部炎症可能会降低痴呆症的风险。因此，关键是要确定 这些脆弱性/恢复力因素对认知健康和拐点的相对贡献 具体的降低风险干预措施可能是最有效的。人类连接组计划(HCP)的发现 表明了一种强烈的正-负种群协变模式，将大脑连接、人口统计 和行为。这个项目提供了一个前所未有的机会，在一个 当生活方式因素开始启动大脑健康下降轨迹的关键转折点。为了澄清 为了解决这些关系，本项目将着重于中老年过渡的下列具体目标： (1)确定中老年过渡期中可改变的脆弱性和弹性因素的影响 (锻炼、睡眠、饮食、压力(与P1)；健康衡量(体重指数、血压、胰岛素 阻力(HbA1c，胆固醇)，对结构连接性(扩散张量成像(DTI)测量； 功能连接性(静息状态功能连接性(RsFC)；任务fMRI)和认知(2)决定 AD危险因素和标记物与可改变的生活方式因素和健康标记物在 用横断面和纵向研究中晚期生命转变中的脑轨迹和认知变化 分析；(3)在AABC中确定最可能的连接大脑和认知结果的结构模型 AD生物标志物、基线认知、年龄、AD风险和生活方式的纵向数据。4)与其他系统的集成 项目和该中心作为一个整体来研究大脑和认知老化的终身、非线性轨迹， 对AD的抵抗力、风险和韧性。为了达到这些目标，我们将对764进行纵向跟踪 中老年(50至80岁)的受试者，包括评估生活方式和韧性的措施 (例如，活动、睡眠、饮食)，并与核心和其他项目协调，以包括其他措施和 与这些目标相关的变量。随着证据的积累，AD风险的缓解可以延迟或预防 对于这种疾病，有必要对痴呆症风险最高的人进行识别、告知和干预。何时启动 早期，即使是相对温和的风险降低，也可能转化为疾病发病率的显著下降。这个项目 提供机会利用经过充分研究的正常老龄化中老年人队列，其中许多人具有 十年的纵向数据。

ABSTRACT FOR PROJECT 2 An effective disease-modifying treatment for Alzheimer’s dementia (AD) or AD related dementias (ADRD) is not available, underscoring the pressing need to identify brain health protective factors that reduce risk for cognitive decline, AD, and ADRD. A critical time that influences the impact of modifiable risk factors is the transition from midlife to late life (50 to 80 years). Research also has demonstrated the role of inflammation in neurodegeneration, and disrupting brain inflammation may reduce dementia risk. It is thus critical to determine relative contributions of these vulnerability/resiliency factors to cognitive health and inflection points when specific risk reduction interventions may be most effective. Findings from the Human Connectome Project (HCP) indicate a strong positive-negative mode of population covariation that links brain connectivity, demographics and behavior. This project offers an unprecedented opportunity to examine such factors longitudinally during a critical inflection point when lifestyle factors begin to initiate a downward brain health trajectory. To elucidate these relationships, this project will address the following specific aims focused on the mid to-late-life transition: (1) Determine the effects of modifiable vulnerability and resilience factors in the mid-to late-life transition (exercise, sleep, diet, stress (with P1); measures of health (Body Mass Index (BMI), blood pressure (BP), insulin resistance (HbA1c), cholesterol), on structural connectivity (measured with Diffusion Tensor Imaging (DTI); functional connectivity(resting state functional connectivity (rsFC); task fMRI) and cognition (2) Determine the unique contributions of AD risk factors and markers vs. modifiable lifestyle factors and health markers on the trajectory of brain and cognitive change across the mid-late life transition using cross-sectional and longitudinal analysis; (3) Identify the most likely structural model that connects brain and cognitive outcomes in the AABC longitudinal data with AD biomarkers, baseline cognitive, age, AD risk and lifestyle. 4) Integration with other projects and the Center as a whole to examine lifetime, non-linear trajectories of brain and cognitive aging, resistance to AD, risk, and resilience. To accomplish these aims, we will perform longitudinal follow-up of 764 subjects in the mid- to late-life transition (ages 50 to 80) and include measures assessing lifestyle and resilience (e.g., actigraphy, sleep, diet) and coordinate with the cores and other projects to include other measures and variables relevant to these aims. With the accumulation of evidence that mitigation of AD risk can delay or prevent the disease, there is a need to identify, inform and intervene in people at greatest dementia risk. When started early, even relatively modest risk reduction may translate to significant declines in disease incidence. This project offers the opportunity to leverage a well-studied cohort of normal aging middle-aged and older adults, many with a decade of longitudinal data.