Brain predictors of mobility and falls in older adults with multiple sclerosis

患有多发性硬化症的老年人活动能力和跌倒的大脑预测因素

• 批准号: 10338168
• 负责人: Roee Holtzer
• 金额: $ 68.49万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10338168
• 关键词: Address; Adult; Adverse effects; Age; Aging; Anisotropy; Atrophic; Attention; Axon; Basal Ganglia; Biological Markers; Brain; Cessation of life; Clinical; Cognition; Cognitive; Diagnosis; Diffuse; Disease; Elderly; Epidemiology; Exhibits; Gait; Gait speed; Hemoglobin; Impaired cognition; Impairment; Individual; Knowledge; Lesion; Link; Locomotion; Memory; Methodology; Methods; Multiple Sclerosis; Neurites; Patients; Pattern; Performance; Prefrontal Cortex; Prevalence; Radial; Recording of previous events; Research; Resources; Risk; Societies; Specific qualifier value; Symptoms; System; Thalamic structure; Thick; Walking; adverse outcome; age group; clinically significant; cognitive control; cognitive function; density; design; disability; executive function; fall injury; fall risk; falls; follow-up; functional near infrared spectroscopy; gray matter; indexing; mind control; motor control; multimodal neuroimaging; multiple sclerosis patient; neuroimaging; novel; novel marker; processing speed; recruit; relating to nervous system; white matter

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.

活动障碍通常是多发性硬化症（MS）最明显的症状