Biological and neural mechanisms of falls

描述(申请人提供)：每年有1/3的65岁以上的社区居民和1/2的80岁以上的人摔倒。老年人跌倒的后果往往是毁灭性的，导致丧失独立性、制度化和过早死亡。 在美国，跌倒每年还造成超过200亿美元的医疗费用。尽管许多针对临床风险因素的跌倒预防策略已经过测试，但它们在减少跌倒方面的成功并不大。目前在衰老方面的跌倒研究主要集中在跌倒的临床预测因素上，对跌倒的潜在生物学和神经机制缺乏了解。来自我们和其他研究的新证据表明，炎症、氧化应激和血管通路中的生物紊乱与步态、平衡和认知障碍的发生有关，这些都是老年人跌倒的主要危险因素。我们假设，异常的生物通路会引发动脉粥样硬化，导致脑血管损伤，从而增加老年人跌倒的风险。我们召集了一个多学科团队进行高质量的研究，以我们广泛的认知和行动能力研究为基础，建立跌倒的生物学和神经机制。我们将从正在进行的老龄化活动中央控制研究中交叉招募530名年龄在65岁及以上的参与者，该研究提供了一种成本和时间高效的策略来研究跌倒的生物和神经机制。这项建议将采用严格的临床评估，其中许多评估是在我们的其他老龄化研究中开发和验证的，以评估跌倒的风险。我们提出了以下三个协同目标，重点是我们共同的主题--生物和神经对衰老跌倒的贡献。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枢微血管病变对跌倒风险的贡献。3)。使用一种创新的功能性近红外光谱(FNIRS)来确定前额叶皮质对跌倒的贡献，该光谱可以在行走时进行成像。虽然跌倒的生物风险因素可能是可以改变的， 数据的匮乏是转化为临床干预措施的关键障碍。虽然许多针对临床风险因素的FAL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并不成功，在现实世界中更是如此。更深入地了解跌倒的潜在生物学机制和神经底物可能会导致更有效的风险识别，并改善目前对老年人跌倒的干预措施的有效性。

DESCRIPTION (provided by applicant): 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.