Brain Predictors of Mobility and Falls in Older Adults with Multiple Sclerosis

行动能力障碍通常是多发性硬化症(MS)最明显的症状 这种疾病的临床特征。跌倒在女士中也是很常见的，失去灵活性和 在MS患者中观察到的频繁跌倒与多种不良反应有关 结果包括残疾和死亡。最近的流行病学证据表明， 多发性硬化症在老年人群中的流行高峰，这可能与共同发生的情况相吻合 衰老和多发性硬化症相关的行动能力和认知能力下降。关于老年人脑部系统的研究 多发性硬化症的流动性和跌倒，特别是在患有多发性硬化症的老年人中，很少。这项建议提供了一个 新的理论和经验方法，专门设计来解决现有的限制 老年MS患者的活动能力和跌倒的研究 我们最重要的假设是前额叶皮质(PFC)和相关的功能回路- 包括基底节和丘脑--以及白质的完整性对认知能力至关重要 机动性的控制。我们的目标是识别在单任务和双任务下行走的大脑系统 确诊为多发性硬化症和多发性硬化症的120名老年人(≥60岁)的跌倒情况和跌倒情况 对照组(60岁，≥)。我们认为根据“神经功能低下”，多发性硬化症患者 在运动过程中表现出较高的HBO2水平，以支持类似或更差的行走 与控件相比的性能。我们进一步假设，较高(即低效)的HBO2水平 在双重任务期间，步行将预测MS患者意外跌倒的风险增加。最后， 白质完整性被认为是导致低效大脑激活的机制 移动。 在目标1中，我们将确定与单任务行走(STW)和 120例多发性硬化患者和120例正常对照的双任务步行(DTW)研究使用DTI，我们将检查 活动期间白质完整性对PFC HBO2模式的调节作用 走路。在目标2中，我们将使用多模式神经成像方法来建立大脑系统 控制120例MS患者和120例健康人的STW和DTW。在《目标3》中，我们将使用 在DTW期间用fNIRS评估PFC HBO2水平，以预测120毫秒之间的事件 患者进行纵向随访(1-5年)。 确定新的和潜在的可修改的老年人跌倒和活动障碍的生物标志物 成人多发性硬化症具有重要的流行病学和临床意义。澄清 控制多发性硬化症老年人行动能力的大脑系统的机械基础将有 对知识的重大影响和对行动能力障碍治疗的重要影响 然后摔倒。

Mobility impairments are often the most visible symptom of Multiple Sclerosis (MS) and the clinical hallmark of the disease. Falls are also very common in MS. The loss of mobility and the frequent falls that are observed in patients with MS are associated with a multitude of adverse outcomes including disability and death. Recent epidemiological evidence suggests a shift in the peak prevalence of MS into older age groups, and this will likely coincide with co-occurring aging and MS-related declines in mobility and cognition. Research concerning brain systems of mobility and falls in MS, notably among older adults with MS, is scarce. This proposal offers a novel theoretical and empirical approach specifically designed to address existing limitations in mobility and falls research in older adults with MS. Our overarching hypothesis is that the prefrontal cortex (PFC) and related functional circuits – including the basal ganglia and thalamus – and white matter integrity are critical for cognitive control of mobility. We aim to identify brain systems of walking under single and dual-task conditions and of falls in 120 older (age≥60) adults with a definite diagnosis of MS and 120 controls (age≥60). We propose that according to “neural inefficiency,” patients with MS will demonstrate higher HbO2 levels during locomotion to support similar or worse walking performance compared to controls. We further postulate that higher (i.e., inefficient) HbO2 levels during dual-task walking will predict increased risk of incident falls among MS patients. Finally, white matter integrity is proposed as mechanism underlying inefficient brain activation during locomotion. In aim 1 we will determine PFC HbO2 patterns associated with Single-Task-Walk (STW) and Dual-Task-Walk (DTW) in 120 MS patients and 120 controls. Using DTI, we will examine the moderating effect of white matter integrity on PFC HbO2 patterns assessed during active walking. In aim 2 we will use multi-modal neuroimaging methods to establish brain systems controlling STW and DTW in 120 MS patients and 120 healthy controls. In aim 3 we will use PFC HbO2 levels, assessed with fNIRS during DTW, to predict incident falls among 120 MS patients over a longitudinal follow-up (years 1-5). Identifying novel and potentially modifiable biomarkers of falls and mobility impairments in older adults with MS is of paramount epidemiological and clinical significance. Elucidating the mechanistic underpinnings of brain systems controlling mobility in older adults with MS will have a major impact on knowledge and important implications for treatment of mobility impairments and falls.