ROEE HOLTZER (2019-05-15 to 2024-02-29) Brain predictors of mobility and falls in older adults with multiple sclerosis. Amount: $1398618
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.
流动性障碍通常是多发性硬化症（MS）最明显的症状和疾病的临床标志。瀑布在MS中也很常见。在MS患者中观察到的活动能力丧失和频繁跌倒与多种不良后果相关，包括残疾和死亡。最近的流行病学证据表明MS的高峰患病率转变为年龄较大的年龄组，这可能与同时出现的衰老和MS相关的活动和认知能力下降相吻合。关于MS的移动性和跌倒的脑系统的研究很少，特别是在患有MS的老年人中。该提案提供了一种新颖的理论和实证方法，专门用于解决现有的流动性限制和老年MS患者的研究。我们的首要假设是前额皮质（PFC）和相关的功能回路？包括基底神经节和丘脑？和白质完整性对于移动性的认知控制至关重要。我们的目标是确定在单任务和双任务条件下行走的大脑系统，以及120名年龄较大（年龄≥60岁）的成年人，他们明确诊断为MS和120名对照（年龄≥60岁）。我们建议根据“神经效率低下”，？与对照组相比，MS患者在运动过程中表现出更高的HbO2水平，以支持相似或更差的行走表现。我们进一步假设在双任务行走期间更高（即低效）的HbO2水平将预测MS患者中事件下降的风险增加。最后，提出白质完整性作为运动期间低效脑激活的机制。在目标1中，我们将确定与120名MS患者和120名对照中的单任务步行（STW）和双任务步行（DTW）相关的PFC HbO2模式。使用DTI，我们将检查白质完整性对主动行走期间评估的PFC HbO2模式的调节作用。在目标2中，我们将使用多模态神经成像方法来建立控制120名MS患者和120名健康对照中的STW和DTW的脑系统。在目标3中，我们将使用在DTW期间用fNIRS评估的PFC HbO2水平来预测120名MS患者在纵向随访（1-5岁）中的事件下降。鉴定具有MS的老年人跌倒和行动障碍的新型和潜在可修饰的生物标志物具有最重要的流行病学和临床意义。阐明控制老年MS患者活动性的大脑系统的机制基础，将对知识和对行动障碍和跌倒治疗的重要影响产生重大影响。
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