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

项目摘要/摘要： 临床步态异常出现在大约35%的社区住宅中 在美国，老年人步态下降加速与许多身体和认知方面的不利因素有关 结果--包括跌倒、残疾、认知能力下降和痴呆症。这样的结果不仅降低了质量 这不仅影响了受影响个人及其家人和朋友的生活，而且还导致卫生保健费用增加。在2000年 老年人跌倒的直接成本超过190亿美元，而在 在美国，老年人因伤害性跌倒而进行的紧急求诊总数为68亿次。2014年，预计成本 在美国，为阿尔茨海默病和相关痴呆症患者提供的正式护理费用为2140亿美元，外加另一笔 家庭成员和其他无偿照顾者提供非正式护理的估计费用为2200亿美元。因此， 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危险因素 可以对个人和社会产生巨大的影响。我们的目标是比较和对比 脑功能和结构轨迹随步态下降和认知功能下降而改变 认知健康的老年人，以及处于认知衰退早期阶段的老年人。我们假设 人类运动控制通路的功能和结构变化--包括补充 运动、岛叶和前额叶皮质区域-步态下降之前(或有更早的变化点)和 认知衰退(假设1a)，以及大脑功能变化先于大脑结构变化 (假设1b)。我们进一步假设，这些地区的功能和结构衰退将更加陡峭或 在患有运动认知风险(MCR)综合征的老年人中有较早的变化点(假设2)-a 以步态缓慢和认知障碍为特征的痴呆症前期综合征--以及较少的老年人 高接触的社会关系和差的社会网络(假设3)。我们将交叉招收200名LonGenity 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次核磁共振扫描(3年 分开；完成了23次基线核磁共振检查)。我们建议增加第三次MRI扫描(3年后)，以允许进行检查 对线性和非线性关系进行评估，并延长年度步态、认知和社交网络测试。 这一建议是创新的，因为它同时检查了两个功能大脑的轨迹 递减(基于任务的功能激活/去激活、静息状态功能连接)和结构性 大脑衰退(灰质体积、皮质厚度、结构连通性)、步态衰退和认知 总体而言，老年人的下降--以及与MCR痴呆前期综合征和社会 尤其是网络。这项建议有可能更好地了解 步态、认知和大脑老化之间的相互关系--并提示有针对性的、 老年、痴呆前期、早期维持步态和认知的适当干预措施 阿尔茨海默病和相关痴呆症。

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.