Neural signatures of healthy and unhealthy aging

 描述（由申请人提供）：生育率下降，婴儿潮一代的老龄化和预期寿命的增加导致人口老龄化。随着人口老龄化，这增加了与年龄有关的疾病对公共卫生的影响，如心血管疾病，2型糖尿病和痴呆症。在晚年治疗未预防的疾病已被证明是昂贵和无效的。因此，需要在中年采取有效的战略，预防与年龄有关的疾病，提高长寿的质量。现在人们知道，可能可预防的风险暴露和与年龄有关的疾病的生理原因出现在儿童时期。这种认识为从童年开始跟踪队列的研究提供了新的科学意义。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，从生命历程的前半期开始。在这些器官系统中，中枢神经系统是不可或缺的，这促使我们建议在达尼丁多学科健康与发展研究中增加神经影像学，这是一项关于成人发育和衰老的问题和积极过程的纵向研究，目前已进入第五个十年。这项研究结合了人口/经济调查，临床质量健康评估，生物银行和全国行政记录（健康，福利，财务）的联系方法。我们建议对出生队列的1004名活体成员实施多模式MRI方案。我们提出的神经成像协议将测量大脑功能，结构和连接的个体差异。我们专注于四个神经回路的枢纽和每一个支持的核心行为能力：（1）杏仁核和情绪/威胁，（2）腹侧纹状体和动机/奖励，（3）海马和记忆，（4）背外侧前额叶皮层和执行控制。通过由此产生的中年神经指标，我们提出了三个主要目标，这些目标将产生有关问题老龄化和成功老龄化的发现：目标1测试前瞻性确定的早期逆境是否与中年神经指标有关。目标2测试神经测量是否与现实世界的行为（例如，储蓄行为），为成功的老龄化做准备。目的3测试神经测量是否与生物老化的加速步伐有关。拟议的工作将通过产生有关年龄相关疾病和成功健康老龄化的神经相关性的发现来提高知识。这些发现有望为预防疾病和加强晚年健康准备提供支持。在拟议的5年项目之后，设想进行后续神经成像。因此，该项目将神经影像学引入了衰老科学的三个及时而充满活力的领域：终身健康的早期规划研究，成功衰老的中年准备研究，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.