Biological and neural mechanisms of falls

跌倒的生物学和神经机制

• 批准号: 8845349
• 负责人: JOE VERGHESE
• 金额: $ 15.23万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8845349
• 关键词: Accounting; Address; Age; Aged, 80 and over; Aging; Atherosclerosis; Attention; Bilateral; Biological; Biological Markers; Biology; Blood Vessels; Cerebrum; Clinical; Clinical assessments; Cognition; Cognitive; Communities; Data; Effectiveness; Effectiveness of Interventions; Elderly; Enrollment; Equilibrium; Fall prevention; Gait; Gait abnormality; Health Care Costs; High Prevalence; Human; Image; Impairment; Incidence; Individual; Inflammation; Inflammatory; Inflammatory Response; Institutionalization; Intervention; Isoprostanes; Knowledge; Lacunar Infarctions; Lead; Lesion; Leukoaraiosis; Link; Malondialdehyde; Measures; Mediating; Microvascular Dysfunction; Modeling; Motor; Near-Infrared Spectroscopy; Oxidative Stress; Participant; Pathology; Pathway interactions; Peripheral Nerves; Pharmaceutical Preparations; Physical Function; Physical activity; Play; Prefrontal Cortex; Premature Mortality; Prevention strategy; Preventive Intervention; Protocols documentation; Reporting; Research; Risk; Risk Factors; Role; Severities; Site; Stroke; Syndrome; Techniques; Testing; Time; Translations; United States; Vascular Diseases; Walking; Work; base; clinical risk; cognitive function; cost; design; disability; economic cost; fall risk; falls; improved; innovation; macrovascular disease; multidisciplinary; neuroimaging; neuromechanism; new technology; public health relevance; relating to nervous system; success

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.

描述（由申请人提供）：每年有三分之一的65岁以上的社区居民和两分之一的80岁以上的居民跌倒。老年人福尔斯跌倒的后果往往是毁灭性的，导致丧失独立性、被送入机构和过早死亡。 福尔斯每年还造成美国超过200亿美元的医疗费用。虽然许多针对临床危险因素的跌倒预防策略已经过测试，但它们在减少福尔斯方面的成功是有限的。目前福尔斯的研究主要集中在福尔斯的临床预测，有一个知识空白的基础生物和神经机制的福尔斯。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的生物学紊乱与步态、平衡和认知障碍的发生有关，这些是老年人福尔斯的主要危险因素。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，增加老年人福尔斯跌倒的风险。我们召集了一个多学科团队进行高质量的研究，以建立福尔斯的生物和神经机制，建立在我们广泛的认知和移动性研究的基础上。我们将交叉招募530名年龄在65岁及以上的参与者，他们来自正在进行的老龄化活动性中央控制研究，该研究提供了一种成本和时间效率高的策略来研究福尔斯的生物和神经机制。这项提案将采用严格的临床评估，许多在我们的其他老化研究中开发和验证，以评估跌倒风险。我们提出了以下三个协同目标集中在我们的共同主题的生物和神经的贡献，福尔斯老化。1）。确定导致福尔斯的生物学机制（炎症、氧化应激和血管通路）。2）。使用最先进的神经影像学技术确定中枢微血管病理学对跌倒风险的贡献。3）。使用创新的功能性近红外光谱（fNIRS）建立前额皮质对福尔斯的贡献，该光谱可以在行走过程中成像。虽然福尔斯的生物风险因素是可以改变的， 缺乏数据是转化为临床干预措施的一个关键障碍。虽然许多针对临床风险因素的跌倒预防策略已经过测试，但它们在减少福尔斯方面的成功在研究环境中是适度的，在真实的世界中更是如此。对福尔斯跌倒的潜在生物学机制和神经基质的更深入理解可能会导致更有效的风险识别，并提高目前老年人跌倒干预措施的有效性。