Biological predictors of brain aging trajectories

项目摘要/摘要 认知能力随年龄变化的程度和速度存在相当大的个体差异。 我们就越能更好地理解影响衰老以及如何影响大脑结构的生物学机制 我们越有能力以针对个人的方式进行有效干预。最重要的是 此更新应用程序的目标是更好地了解炎症、血管、神经退行性变和 生活方式/行为对大脑老化轨迹的这种临床上重要的多样性做出了贡献。我们建议 继续跟踪我们由250名功能完好的老年正常人组成的深度表型队列，并提供详细的 认知、神经成像和生物特征超过两个额外的时间点。我们的首要目标是定义 生物和生活方式变量通过分离和相互作用的途径影响与年龄相关的 脑结构和功能我们的第二个目标将确定创新的血浆标志物的预测价值 与阿尔茨海默氏症和神经退行性变有关的蛋白质。我们的第三个目标将包括创新、 客观、实时地测量睡眠和体力活动。实现这些目标将具有高度的 对这一领域产生了重大影响。验证血浆病理生物标志物并阐明复杂的相互作用 了解影响大脑衰老轨迹的因素将有助于更好地预测和预防不良脑损伤 老龄化和告知针对个人的干预措施。

PROJECT SUMMARY /ABSTRACT There is considerable individual variability in how much and how quickly cognitive abilities change with age. The better we understand the biological mechanisms that influences if and how aging affects brain structure and function, the more able we will be to intervene effectively in a person-specific manner. The overarching goal of this renewal application is to better understand the inflammatory, vascular, neurodegenerative, and lifestyle/behavioral contributions to this clinically important diversity in brain aging trajectories. We propose to continue following our deeply phenotyped cohort of 250 functionally intact older normals with our detailed cognitive, neuroimaging, and biometric characterizing over two additional time points. Our first aim is to define the separate and interactive pathways by which biologic and lifestyle variables influence age-related decline in brain structure and function Our second aim will determine of predictive value of innovative plasma markers of proteins associated with Alzheimer’s and neurodegeneration. Our third aim will incorporate innovative, objective, real-time measures of sleep and physical activity. Accomplishing these aims will have a highly significant impact on the field. Validating plasma biomarkers of pathology and clarifying the complex interplay of factors that influence brain aging trajectories will lead to better prediction and prevention of adverse brain aging and inform person-specific interventions.