Trajectories and modifiable risk factors of brain, gait, and cognitive decline in aging and pre-dementia

项目总结/摘要： 临床步态异常存在于约35%的社区居住 在美国的老年人中，加速的步态衰退与许多不利的身体和认知功能有关。 结果-包括福尔斯、残疾、认知能力下降和痴呆。这样的结果不仅降低了质量， 这不仅影响了受影响的个人、他们的家人和朋友的生活，而且还导致医疗保健费用增加。2000年 老年人福尔斯的直接成本超过190亿美元， 在美国，老年人因跌倒受伤而急诊的人数达到68亿。2014年，预计成本 在美国，对阿尔茨海默病和相关痴呆症患者的正式护理费用为2140亿美元， 2200亿美元用于家庭成员和其他无报酬照顾者提供的非正式护理。因此，我们认为， 更好地了解衰老过程中大脑、步态和认知能力下降的轨迹和可改变的风险因素 会对个人和社会产生巨大的影响。我们的目标是比较和对比 随着步态下降和认知能力下降， 认知健康的老年人和处于认知衰退早期的老年人。我们假设 人类运动控制途径的功能和结构变化--包括补充的 运动、岛叶和前额叶皮层区域-先于步态衰退（或具有更早的变化点）， 认知能力下降（假设1a），功能性大脑变化先于结构性大脑变化 （假设1b）。我们进一步假设，这些区域的功能和结构衰退将更陡峭， 在患有运动性认知风险（MCR）综合征的老年人中有更早的变化点（假设2）- a 痴呆前期综合征的特征是缓慢的步态和认知投诉-以及老年人很少 高接触的社会关系和贫穷的社交网络（假设3）。我们将交叉入组200名LonGenity患者 研究参与者每年进行长达10年的步态和认知测试，并计划进行2次MRI扫描（3年 完成23次基线MRI）。我们建议增加第三次MRI扫描（3年后）以允许检查 线性和非线性关系，并延长年度步态，认知和社会网络测试。 这项建议是创新的，因为它同时检查两个功能大脑的轨迹 下降（基于任务的功能激活/失活，静息状态功能连接）和结构 大脑衰退（灰质体积、皮质厚度、结构连接性）、步态衰退和认知能力下降 一般老年人的下降-因为它们与MCR痴呆前综合征有关， 尤其是网络。这一建议有可能使人们更好地了解 步态，认知和大脑老化之间的相互关系-并告知目标的发展， 适当排序，干预措施，以维持步态和认知老化，前痴呆，早期 阿尔茨海默氏病及相关痴呆症。

PROJECT SUMMARY/ABSTRACT: Clinical gait abnormalities are present in about 35% of community-dwelling older adults in the US, and accelerated gait decline is associated with many adverse physical and cognitive outcomes - including falls, disability, cognitive decline, and dementia. Such outcomes not only reduces the quality of life of affected individuals, their families, and friends, but also leads to increased health care costs. In 2000 the direct costs of falls among older adults exceeded $19 billion, and the cost of health care following an emergency visit for an injurious fall among older adults totaled 6.8 billion in the US. In 2014, the estimated cost of formal care to people with Alzheimer's disease and related dementias was 214 billion in the US, plus another 220 billion in estimated costs for informal care provided by family members and other unpaid caregivers. Hence, a better understanding of trajectories, and modifiable risk factors, of brain, gait, and cognitive decline in aging can have a tremendous impact on individuals as well as to society. We aim to compare and contrast trajectories of functional and structural brain changes with gait decline and cognitive decline in cognitively-healthy older adults, and older adults in the early stages of cognitive decline. We hypothesize that functional and structural changes in the control pathway of human locomotion – including supplementary motor, insular, and prefrontal cortex regions – precede (or have earlier change points than) gait decline and cognitive decline (Hypothesis 1a), and that functional brain changes precede structural brain changes (Hypothesis 1b). We further hypothesize that functional and structural decline in these regions will be steeper or have earlier change points in older adults with the motoric cognitive risk (MCR) syndrome (Hypothesis 2) – a pre-dementia syndrome characterized by slow gait and cognitive complaint – as well as in older adults with few high-contact social relationships and poor social networks (Hypothesis 3). We will cross-enroll 200 LonGenity study participants with up to 10 years of annual gait and cognitive testing, and 2 planned MRI scans (3 years apart; 23 baseline MRIs completed). We propose to add a third MRI scan (3 years later) to permit examination of both linear and non-linear relationships, and to extend annual gait, cognitive and social network testing. This proposal is innovative because it simultaneously examines trajectories of both functional brain decline (task-based functional activation/deactivation, resting-state functional connectivity) and structural brain decline (gray matter volume, cortical thickness, structural connectivity), gait decline, and cognitive decline in older adults in general – and as they relate to the MCR pre-dementia syndrome, and social networks in particular. This proposal has the potential to provide a better understanding of the interrelationships between gait, cognition and brain aging – and inform the development of targeted, and appropriately sequenced, interventions for maintaining gait and cognition in aging, pre-dementia, early Alzheimer's disease and related dementias.