Biological and neural mechanisms of falls

跌倒的生物和神经机制

JOE VERGHESE (2013-09-01 to 2018-05-31) $3,643,940

Project ID: R01AG044007 (NIA)

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Abstract

One in three community dwelling people over age 65 and one in two over age 80 fall each year. The consequences of falls among older adults are often devastating, resulting in loss of independence, institutionalization and premature mortality. Falls also are responsible for greater than 20 billion dollars a year in healthcare costs in the United States. Although many fall prevention strategies targeted against clinical risk factors have been tested, their success in reducing falls has been modest. Current falls research in aging is mostly focused on clinical predictors of falls and there is a knowledge gap regarding underlying biological and neural mechanisms of falls. Emerging evidence from our and other studies implicates biological derangements in inflammation, oxidative stress, and vascular pathways in the occurrence of disorders of gait, balance, and cognition, which are major risk factors for falls in older adults. We hypothesize that abnormal biological pathways initiate atherosclerosis leading to cerebral vascular damage that increases risk of falls in older adults. We draw together a multidisciplinary team to conduct high-quality research to establish biological and neural mechanisms of falls building on our extensive cognitive and mobility research. We will cross-enroll 530 participants, age 65 and older, from the ongoing Central Control of Mobility in Aging study offering a cost and time efficient strategy to study biological and neural mechanisms of falls. This proposal will employ rigorous clinical assessments, many developed and validated in our other aging studies, to assess fall risk. We propose the following three synergistic aims focusing on our common theme of biological and neural contributions to falls in aging. 1). Determine biological mechanisms (inflammation, oxidative stress, and vascular pathways) contributing to falls. 2). Establish contributions of central microvascular pathology to fall risk using state of the art neuroimaging techniques. 3). Establish the contribution of the prefrontal cortex to falls using an innovative functional near infrared spectroscopy (fNIRS), that enables imaging during walking. While biological risk factors for falls are potentially modifiable, the paucity of data is a critical barrier for translation to clinical interventions. While many fal prevention strategies targeted against clinical risk factors have been tested, their success in reducing falls has been modest in research settings and even less so in the real world. A deeper understanding of underlying biological mechanisms and neural substrates for falls may lead to more efficient risk identification and improve the effectiveness of current interventions for fallsin older adults.

每年有超过三十岁的社区居民中有三分之一的人和80岁以上的两个人。老年人跌倒的后果往往具有破坏性，导致丧失独立性，制度化和过早死亡。瀑布每年在美国的医疗保健费用也超过200亿美元。尽管针对临床危险因素的许多跌倒预防策略已经过测试，但它们在减少跌倒方面的成功是适度的。目前针对衰老的研究主要集中在跌倒的临床预测因素上，并且关于跌倒的潜在生物学和神经机制存在知识差距。我们和其他研究的新证据表明，在步态，平衡和认知障碍的发生中，炎症，氧化应激和血管通路的生物紊乱是老年人跌倒的主要危险因素。我们假设异常的生物学途径引发动脉粥样硬化，导致脑血管损伤，增加老年人跌倒的风险。我们汇集了一个多学科团队，进行高质量的研究，建立基于我们广泛的认知和流动研究的瀑布的生物和神经机制。我们将对正在进行的老龄化流动中心控制研究中的530名65岁及以上的参与者进行交叉登记，为研究跌倒的生物和神经机制提供成本和时间有效的策略。该提案将采用严格的临床评估，许多在我们的其他老龄化研究中得到开发和验证，以评估跌倒风险。我们提出以下三个协同目标，重点关注我们对老龄化衰退的生物和神经贡献的共同主题。 1）。确定导致跌倒的生物机制（炎症，氧化应激和血管通路）。 2）。使用最先进的神经成像技术建立中心微血管病理学对降低风险的贡献。 3）。使用创新的功能性近红外光谱（fNIRS）确定前额叶皮层对跌倒的贡献，使其能够在行走时进行成像。虽然跌倒的生物风险因素可能是可修改的，但缺乏数据是临床干预翻译的关键障碍。虽然针对临床风险因素的许多预防策略已经过测试，但它们在减少跌倒方面的成功在研究环境中是适度的，在现实世界中则更少。更深入地了解跌倒的潜在生物学机制和神经基质可以更有效地识别风险，并提高目前对老年人跌倒的干预措施的有效性。