Neural signatures of healthy and unhealthy aging

 描述(申请人提供)：生育率下降，婴儿潮一代的老龄化，以及预期寿命的增加正在导致人口老龄化。随着人口老龄化，这增加了与年龄相关的疾病对公共健康的影响，如心血管疾病、2型糖尿病和痴呆症。事实证明，在晚年治疗未预防的疾病既昂贵又无效。因此，需要在中年时期采取有效的战略，以预防与年龄有关的疾病，并提高较长寿命的质量。现在已经知道，与年龄相关的疾病的潜在可预防风险暴露和生理原因出现在儿童时期。这一认识为从小跟踪队列的研究赋予了新的科学意义。现在还知道，与年龄有关的疾病的发病机制涉及器官系统逐渐积累的损害，从生命过程的前半部分开始。在这些器官系统中，中枢神经系统是不可或缺的，这促使我们提议将神经成像添加到达尼丁多学科健康与发展研究中，这是一项关于成人发育和衰老的有问题的和积极的过程的纵向研究，出生队列现已进入第五个十年。这项研究结合了人口/经济调查、临床质量健康评估、生物资料库以及与全国行政记录(健康、福利、财务)的联系。我们建议对出生队列中的1004名在世成员实施多模式磁共振成像方案。我们建议的神经成像方案将测量大脑功能、结构和连接性的个体差异。我们专注于四个神经回路的中枢和每个核心行为能力的支持：(1)杏仁核和情绪/威胁，(2)腹侧纹状体和动机/奖励，(3)海马体和记忆，(4)背外侧前额叶皮质和执行控制。通过由此产生的中年神经测量，我们提出了三个主要目标，将产生关于问题和成功老龄化的结果：目标1测试预期确定的早期生活逆境是否与中年神经测量有关。目的2测试神经测量是否与为成功衰老做准备所必需的真实世界行为(例如，储蓄行为)联系在一起。目的3检验神经措施是否与生物衰老速度加快有关。这项拟议的工作将通过产生关于与年龄相关的疾病的神经相关性和成功的健康老龄化的发现来提高知识。这些发现预计将支持预防疾病和加强晚年福祉的准备。除了拟议的5年项目外，还将设想后续的神经成像。因此，该项目将神经成像带入了老龄化科学的三个及时而充满活力的领域：终身健康的早期生命规划研究，为成功衰老做好中年准备的研究，以及将大脑功能与身体健康联系起来的身心研究。

 DESCRIPTION (provided by applicant): Declining fertility rates, aging of the baby-boomers, and increasing life expectancy are leading to population aging. As the population ages, this increases the public-health impact of age-related conditions, such as cardiovascular disease, type 2 diabetes, and dementia. Treating un-prevented diseases in late life has proven costly and ineffective. Consequently, effective strategies are needed in midlife to prevent age-related diseases and to improve the quality of longer lives. It is now known that potentially preventable risk exposures and physiological causes of age-related disease emerge in childhood. This recognition lends new scientific significance to studies that have followed cohorts from childhood. It is also now known that the pathogenesis of age-related diseases involves gradually accumulating damage to organ systems, beginning in the first half of the life course. Of these organ systems, the central nervous system is integral, prompting our proposal to add neuroimaging to the Dunedin Multidisciplinary Health & Development Study, a longitudinal study of both problematic and positive processes of adult development and aging, in a birth cohort now entering its fifth decade. This study combines methods of demographic/economic surveys, clinical-quality health assessments, biobanking, and linkage to nationwide administrative records (health, welfare, finances). We propose to administer a multimodal MRI protocol to the 1004 living members of the birth cohort. Our proposed neuroimaging protocol will measure individual variation in brain function, structure, and connectivity. We focus on the hubs of four neural circuits and the core behavioral capacities each supports: (1) the amygdala and emotion/threat, (2) the ventral striatum and motivation/reward, (3) the hippocampus and memory, and (4) the dorsolateral prefrontal cortex and executive control. With the resulting midlife neural measures, we propose three primary aims that will generate findings about problematic and successful aging: Aim 1 tests whether prospectively ascertained early- life adversity is linked to midlife neural measures. Aim 2 tests whether neural measures are linked to real-world behaviors (e.g., saving behavior) necessary to prepare for successful aging. Aim 3 tests if neural measures are related to the accelerated pace of biological aging. The proposed work will improve knowledge by generating findings about the neural correlates of age-related diseases and successful healthy aging. These findings are expected to support preventing disease and enhancing preparedness for wellbeing in late life. Beyond the proposed 5-year project, follow-up neuroimaging is envisaged. This project thus brings neuroimaging into three timely and vigorous areas of aging science: the study of early-life programming of lifelong health, the study of midlife preparation for successful aging, and mind-body research linking brain function to physical health.