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

活动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福尔斯在多发性硬化症中也很常见。 在MS患者中观察到的频繁福尔斯与多种不良反应相关， 结果包括残疾和死亡。最近的流行病学证据表明， MS在老年人群中的患病率达到高峰，这可能与同时发生的 衰老和MS相关的活动性和认知能力下降。关于脑系统的研究 MS患者的活动性和福尔斯，特别是在患有MS的老年人中，是罕见的。该提案提供了一个 新的理论和经验方法，专门设计来解决现有的限制， 老年MS患者的活动性和福尔斯研究。 我们的首要假设是，前额叶皮层（PFC）和相关的功能电路- 包括基底神经节和丘脑-和白色物质的完整性是至关重要的认知 控制流动性。我们的目标是确定在单任务和双任务下行走的大脑系统 120名确诊为MS的老年人（年龄≥60岁）和120名确诊为MS的老年人（年龄≥60岁）的健康状况和福尔斯跌倒情况 对照组（年龄≥60岁）。我们建议，根据“神经低效”，MS患者将 在运动过程中表现出更高的HbO 2水平，以支持类似或更差的行走 与对照组相比，我们进一步假设，更高（即，效率低下）HbO 2水平 将预测MS患者中意外福尔斯跌倒的风险增加。最后， 白色物质的完整性被认为是脑激活效率低下的机制， 运动 在目标1中，我们将确定与单任务步行（STW）相关的PFC HbO 2模式， 在120名MS患者和120名对照中进行双任务步行（DTW）。使用DTI，我们将检查 活动期间评估的白色物质完整性对PFC HbO 2模式的调节作用 走路在aim 2中，我们将使用多模态神经成像方法来建立大脑系统 控制120名MS患者和120名健康对照的STW和DTW。在目标3中，我们将使用 DTW期间使用fNIRS评估的PFC HbO 2水平，用于预测120例MS的意外福尔斯 纵向随访（1-5年）的患者。 鉴定老年人福尔斯和活动障碍的新的和潜在的可改变的生物标志物 成年MS患者具有重要的流行病学和临床意义。阐明 控制MS老年人活动性的大脑系统的机械基础将具有 对知识的重大影响和对行动障碍治疗的重要意义 和福尔斯。

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.