Resilience to Mobility Impairment: Neural Correlates and Protective Factors

对行动障碍的恢复能力：神经相关因素和保护因素

• 批准号: 9085177
• 负责人: HOWARD J AIZENSTEIN
• 金额: $ 13.62万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9085177
• 关键词: Accounting; Adult; Age; Aging; Attenuated; Blood Pressure; Body Composition; Boxing; Brain; Cardiopulmonary; Cessation of life; Characteristics; Chronic; Cognitive; Color; Cross-Sectional Studies; Data; Elderly; Employee Strikes; Epidemiologic Methods; Epidemiologic Studies; Financial compensation; Gait; Glucose; Health; High Prevalence; Hospitalization; Image; Impairment; Individual; Inflammatory; Interleukin-6; Intervention Studies; Light; Lower Extremity; Magnetic Resonance Imaging; Maintenance; Measures; Methodology; Methods; Modeling; Neurophysiology - biologic function; Parents; Parietal; Participant; Pattern; Peripheral Nerves; Physical Function; Physically Handicapped; Prevalence; Preventive Intervention; Research Project Grants; Risk; Risk Factors; Speed; Stroke; Structural defect; Structure; Survival Rate; Testing; Text; Time; Walking; White Matter Hyperintensity; Work; base; cost; disability; fasting glucose; information processing; muscle strength; neural correlate; neuroimaging; processing speed; relating to nervous system; resilience

DESCRIPTION (provided by applicant): Slowing gait and difficulty walking are major and common problems of older adults, they worsen with age and they are associated with greater risk of disability, hospitalization and death. There is strong emergent evidence that structural brain abnormalities, such as white matter hyperintensities (WMH), are associated with lower- extremity mobility limitations. Our preliminary data suggest there is a striking high prevalence of 'resilient' elderly, who have preserved mobility and function despite substantial WMH. In two of our independent studies, more than 40% of individuals with substantial WMH have faster than expected mean gait, "normal" physical function and greater 10-year survival rate. These adults also have "normal" information-processing speed, a cognitive domain strongly related to mobility. We propose that this apparent resilience is related to unique neural activation patterns and to slower accrual of micro-structural abnormalities within critical mobility-related regions (Aim 1). These features are not visible on standard structural MRI obtained at one time point and require advanced longitudinal MRI methodology. Based on previous work and our pilot work we hypothesize that higher neural activation offsets the adverse impact of overall WMH on function (Aim 2). Aim 3 will explore the relationship of risk factors and resilience. In particular, we will test whether slower longitudinal worsening of risk factors (blood pressure, interleukine-6 and glucose) can enhance resilience, by slowing down the accrual of micro-structural abnormalities. Although it is known that greater cross-sectional levels of these risk factors are associated with WMH the impact of their longitudinal trajectories on brain functional and micro-structural characteristics has not been examined in large groups of older adults. In this dual-PI project, Drs. Rosano and Aizenstein propose to acquire a repeat brain MRI in older adult participants of a parent longitudinal NIA epidemiologic study - the Health ABC study (Health, Aging and Body Composition Study) ongoing since 1996. Participants have received a 1st brain MRI in 2007-08 with measures of micro-structure (PI: Dr. Rosano, K23AG028966-01, R01 AG029232). The proposed 2nd MRI will measure brain function (neural activation) in addition to micro-structure. This study cost-effectively leverages longitudinal data on cardiometabolic and inflammatory risk factors, as well as hospitalization and strokes ascertained for 14 years. While Dr. Rosano's MRI study is ongoing, it is absolutely critical to obtain a 2nd MRI to measure longitudinal microstructural changes, maximize participants' retention and minimize costs. This proposal differs from Dr. Rosano's current study of cross-sectional structural brain measures, because it will focus on functional (neural activation) and longitudinal micro-structural changes. Results from this research project may shed light on the mechanisms underlying physical disability and may help us prepare prevention and intervention studies.

描述（由申请人提供）：步态缓慢和行走困难是老年人的主要和常见问题，这些问题随着年龄的增长而恶化，并且与更大的残疾、住院和死亡风险相关。有强有力的新证据表明，脑结构异常，例如白质高信号（WMH），与下肢活动受限有关。我们的初步数据表明，“有弹性”老年人的患病率惊人地高，尽管他们的 WMH 很高，但他们仍保留了活动能力和功能。在我们的两项独立研究中，超过 40% 的患有大量 WMH 的人具有比预期更快的平均步态、“正常”的身体功能和更高的 10 年生存率。这些成年人还具有“正常”的信息处理速度，这是与移动性密切相关的认知领域。我们认为，这种明显的弹性与独特的神经激活模式以及关键移动相关区域内微观结构异常的缓慢增长有关（目标 1）。这些特征在某一时间点获得的标准结构 MRI 上不可见，需要先进的纵向 MRI 方法。根据之前的工作和我们的试点工作，我们假设较高的神经激活可以抵消整体 WMH 对功能的不利影响（目标 2）。目标 3 将探讨风险因素与复原力的关系。特别是，我们将测试风险因素（血压、白细胞介素6和血糖）纵向恶化速度的减缓是否可以通过减缓微观结构异常的累积来增强恢复能力。尽管众所周知，这些危险因素的更大横截面水平与 WMH 相关，但其纵向轨迹对大脑功能和微观结构特征的影响尚未在大群老年人中进行研究。在这个双 PI 项目中，博士。 Rosano 和 Aizenstein 提议对父母纵向 NIA 流行病学研究（自 1996 年以来一直在进行的健康 ABC 研究（健康、老龄化和身体成分研究））的老年人参与者进行重复脑部 MRI 扫描。参与者已于 2007 年 8 月接受了第一次脑部 MRI 测量，并测量了微观结构（PI：Rosano 博士，K23AG028966-01，R01） AG029232）。拟议的第二次 MRI 除微观结构外还将测量大脑功能（神经激活）。这项研究经济高效地利用了 14 年来确定的心脏代谢和炎症危险因素以及住院和中风的纵向数据。虽然罗萨诺博士的 MRI 研究正在进行中，但获得第二次 MRI 来测量纵向微观结构变化、最大限度地提高参与者的保留率并最大限度地降低成本绝对至关重要。该提议与罗萨诺博士目前对大脑横截面结构测量的研究不同，因为它将重点关注功能（神经激活）和纵向微观结构变化。该研究项目的结果可能揭示身体残疾的机制，并可能帮助我们准备预防和干预研究。