Vascular Disease Risk Factors and MS Progression: A Study of Brain Metabolism

血管疾病危险因素和多发性硬化症进展：脑代谢研究

• 批准号: 9928736
• 负责人: VIJAYSHREE YADAV
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9928736
• 关键词: Address; Affect; American; Antiinflammatory Effect; Atrophic; Blood Volume; Blood flow; Brain; Caring; Cerebrovascular Circulation; Cerebrum; Chronic; Clinical; Clinical Trials; Controlled Study; Data; Development; Diabetes Mellitus; Diagnosis; Diet; Disease; Disease Progression; Dose; Effectiveness; Enrollment; Gait; Goals; Health Sciences; Heart Diseases; Hyperlipidemia; Hypertension; Image; Imaging Device; Impairment; Inflammatory; Intervention; Intervention Studies; Life Style; Magnetic Resonance Imaging; Measurement; Measures; Metabolism; Mitochondria; Modification; Multiple Sclerosis; Nerve Degeneration; Neuraxis; Neurologic; Oregon; Pathogenesis; Patients; Perfusion; Peripheral Vascular Diseases; Phosphorus; Play; Preventive Intervention; Progressive Disease; Quality of life; Registries; Research; Research Design; Research Methodology; Research Proposals; Respondent; Risk; Risk Factors; Role; Site; Surveys; System; Techniques; Time; United States; Universities; Vascular Diseases; Veterans; Walking; aged; arm; base; brain metabolism; cerebral atrophy; cohort; design; disability; disorder risk; gray matter; hypercholesterolemia; imaging study; improved; inorganic phosphate; magnetic resonance spectroscopic imaging; mitochondrial dysfunction; multiple sclerosis treatment; novel; public health relevance; response; treatment program; vascular risk factor

 DESCRIPTION: Recent studies suggest that presence of vascular disease risk factors (VDRF) such as diabetes, hypertension, hyperlipidemia, peripheral vascular disease and heart disease can significantly increase the risk of disability progression in multiple sclerosis (MS). There appears to be a dose-response relationship between VDRF and MS disability with the presence of a single VDRF increasing the risk of early gait disability by 51% and the presence of 2 of these conditions increasing the risk to 228%. Among Veterans, VDRF are highly prevalent. In the last two years, among the 19,282 Veterans with MS who received care within the VA system, ~9300 had hyperlipidemia, ~9200 suffered from hypertension and ~3500 had diabetes mellitus. Approximately 5900 MS Veterans had both hypertension and hyperlipidemia. Increasingly, evidence indicates mitochondrial dysfunction and resultant deficiencies in ATP and other high energy phosphorus metabolites contribute to neurodegeneration in MS. Our collaborator Dr. William Rooney at the Oregon Health & Science University Advanced Imaging Research Center has developed techniques to measure high energy phosphorus (HEP) metabolites and cerebral blood flow using a 7 Tesla (T) magnetic resonance imaging (MRI) instrument and demonstrated that people with MS have gray matter deficiencies in HEP metabolites as well as cerebral blood flow abnormalities. The purpose of this research is to determine if VDRF are associated with increased abnormalities in cerebral blood flow and metabolism in people with MS as assessed with high-field brain MRI and if these abnormalities contribute to brain atrophy and clinical disease progression in MS. The overriding hypothesis of this project is that vascular risk factors in MS increase the rate of disease progression and do so by decreasing gray matter metabolism and blood flow and worsening brain atrophy. To address this hypothesis the following aims will be achieved: Specific Aim 1: Using matched cohorts, determine whether Veterans with MS with VDRF in comparison with those without VDRF have decreased cerebral blood flow and volume detected by MRI and high energy phosphate metabolites in cerebral gray matter assessed by 31P magnetic resonance spectroscopic imaging (MRSI). Specific Aim 2: Determine if brain atrophy progresses faster in Veterans with MS and VDRF than those without VDRF and whether 31P MRSI and cerebral blood flow deficits are associated with an increased rate of brain atrophy. Specific Aim 3: Determine if clinical impairment, disability and quality of life deteriorates faster in Veterans with MS and VDRF than those without VDRF and whether 31P MRSI and cerebral blood flow deficits are associated with an increased rate of disease progression. Research Design and Methods: We propose a longitudinal, quantitative MRI study using 31P MRSI assessing mitochondrial function and perfusion measurements to quantify blood volume and flow to investigate whether MS Veterans with VDRF in comparison with those without VDRF have reduced cerebral blood flow and volume, reduced high energy phosphorus metabolites, and accelerated brain atrophy, clinical impairment and disability. This will be a 3-year long controlled study with a single-site, mixed design (cross sectional and longitudinal) with two arms. MRI data will be collected at baseline, 12, 24 and 36 months. We will enroll a total of 60 MS subjects with goal to have 30 subjects in each arm: 1) MS subjects with VDRF; 2) MS subjects without VDRF. MS Subjects aged 40-65 years will be included and may or may not be on disease modifying therapy. The results of these studies will provide the basis for designing a clinical trial to study if interventions aimed at improving VDRF can reduce the risk of disease progression among MS Veterans.

 描述： 最近的研究表明，存在血管疾病风险因素（VDRF），例如糖尿病，高血压，高脂血症，周围血管疾病和心脏病，可以显着增加多发性硬化症（MS）的残疾进展风险。 VDRF与单个VDRF的存在之间的关系将早期步态障碍的风险增加了51％，以下插件中的Thesence of 2将VDRF的风险增加到228％在VA系统内拥有MS的19,282名退伍军人中，〜9200人患有高度疾病，患有3500 d糖尿病。在T -ordergon女士中，先进的成像研究中心使用7 Tesla（T）磁共振成像（MRI）仪器开发了技术ES和脑血流。 VDRF与患有屁股患者的脑血流和代谢异常的增加有关：野外大脑以及这些异常是否有助于大脑，并且在该项目的重叠中，该项目中的疾病进展是MS中的血管RIZK的速度会增加速度的速度。疾病。在31p磁光谱成像（MRSI）的Cerebolil灰物质中，确定脑部的脑部对MS和VDRF THAN的速度是否更快，而VDRF THAN的速度是否与31p MRSI和Cereral血液流量缺陷有关。在MS和VDRF的退伍军人中，残疾和生活质量比WDRF的退伍军人更快地恶化，以及与疾病进展的疾病进展相关的31p MRSI和Cererebal血流缺陷，以评估MITHDRIAL功能。与VDRF相比，与VDRF的TOL TOL MS降低了Ceredubol的损害和残疾。 两个武器将在基线收集12、24和36个月。 -65您将被包括在内，也可能不会在疾病中改变疗法。退伍军人女士的进步。