Curcumin and Yoga Exercise Effects in Veterans at Risk for Alzheimer's Disease

姜黄素和瑜伽运动对有阿尔茨海默病风险的退伍军人的影响

基本信息

批准号：
8976082
负责人：
SALLY ANN FRAUTSCHY
金额：
--
依托单位：
VA GREATER LOS ANGELES HEALTHCARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8976082
关键词：
Activities of Daily Living Admission activity Aerobic Aerobic Exercise Age Aging Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease risk Animals Anti-Inflammatory Agents Anti-inflammatory Antihypertensive Agents Antioxidants Apolipoprotein E Attention Behavioral Biochemical Biological Assay Biological Availability Biological Markers Blood Blood specimen Brain Brain imaging Brain-Derived Neurotrophic Factor Caring Cause of Death Cerebrum Clinical Clinical Trials Cognition Cognitive Complement Control Groups Curcumin Data Degenerative Disorder Disease Progression Documentation Dose Double-Blind Method Dropout Drug Formulations Early Intervention Ensure Epidemiologic Studies Epidemiology Evaluation Exercise Feedback Future Gender Genetic Genotype Heart Rate Home environment Human Impaired cognition Inflammatory Insulin Insulin-Like Growth Factor I Intervention Lead Longitudinal Studies Maximum Heart Rate Measurement Measures Medical Memory Memory Loss Mental Depression Methods Monitor Neurologic Neuropsychological Tests Nursing Homes Onset of illness Oral Outcome Outcome Study Participant Pathogenesis Pathology Pathway interactions Pharmaceutical Preparations Pharmacotherapy Phase II Clinical Trials Physical activity Placebo Control Placebos Plasma Population Positron-Emission Tomography Post-Traumatic Stress Disorders Prevention trial Proteins Quality of life Questionnaires Randomized Rehabilitation therapy Relative (related person)Reporting Resistance Risk Role Social Interaction Staging Supplementation Sweat Sweating Tauopathies The Sun Therapeutic Time Training Training Programs Translations Treadmill Tests Treatment outcome Veterans Work Yoga apolipoprotein E-4 base cohort cost design disability executive function exhaustion glucose metabolism imaging biomarker improved indexing instructor meetings mild cognitive impairment multi-site trial neuropathology neuropsychological neurotrophic factor novel patient population phase 2 study phase II trial pre-clinical programs response strength training sustained attention synergism tau Proteins treatment response trial design uptake

项目摘要

DESCRIPTION (provided by applicant): This 12-month randomized double-blind placebo-controlled early Phase II study of older veterans with mild cognitive impairment (MCI) seeks to investigate the role of curcumin for the prevention of Alzheimer's Disease (AD). MCI often represents incipient AD, as underlying AD neuropathology is common in MCI. Over the first 6 months of the study, we will assess curcumin effects on blood-based biomarkers, brain glucose metabolism, and cognitive and functional parameters predictive of AD risk. Preclinical data suggest curcumin targets early and late steps in AD pathogenesis through its anti-oxidant, anti-inflammatory, and anti-tau/A� aggregate activities. Prior studies of curcumin in AD were limited by poor uptake, but we will use a novel curcumin formulation to achieve previously established target free curcumin blood levels, facilitating delivery to the brain. Over the second 6 months of this study, we will assess the potential for synergism between curcumin treatment and aerobic exercise on our biomarker and clinical indices of AD risk. Exercise improves some aspects of cognition and increases IGF-1 and BDNF levels in the brain. These effects are likely to be potentiated by curcumin, which, in addition to its other effects, reduces insulin/neurotrophic factor resistance. General Design: We will examine the effects of 12 months of curcumin supplementation on a panel of plasma biomarkers identified in both the UCLA and ADNI MCI cohorts as indicative of AD risk. Plasma will be collected at 0, 6 and 12 months. Additional endpoints include neuropsychological, behavioral, and functional assessments at 0, 6 and 12 months and FDG-PET brain imaging at 0 and 6 months. Since physical activity levels may independently modulate rates of progression to AD, the second half of the trial will assess for potential additive benefits derived from an aerobi exercise enrichment program. We have chosen Yoga instead of typical treadmill exercise because it includes both resistance training and aerobic poses in specific sequences that may help sustain attention and reduce attrition. Standard Yoga sequences (Sun Salutations) are equivalent to moderate aerobic exercise, and Yoga studies have lower dropout rates than other comparable exercise trials. In the aerobic yoga class, by one month of training, instructors will increase intensity of practice to ensure target heart rates (60-80% of maximum heart rate) are met and subjects are sweating prior to beginning of cool-down sequence. The non-aerobic yoga group controls for potential confounds such as social interaction and active participation and may improve indices of quality of life and depression (compared to baseline), but is unlikely to provide sufficient exercise to improve biomarker or MCI-relevant clinical indices. Objectives: The specific aims are to determine the impact of 12 months of curcumin supplementation on potential plasma biomarkers of AD, brain glucose metabolism, and cognitive, behavioral, and functional endpoints in older veterans with MCI (Aim 1), and to determine whether the addition of an aerobic exercise program can further potentiate the effects of curcumin supplementation (Aim 2). Hypotheses: We hypothesize that curcumin supplementation will improve cerebral glucose metabolism at 6 months, modify blood-based biomarkers of AD risk at 6 and 12 months, and improve cognitive, behavioral, and functional endpoints at 12 months. We further hypothesize that more substantial biomarker and clinical improvements will be seen in the curcumin + aerobic Yoga treatment group relative to the other treatment groups. Potential Outcomes: This work will help evaluate impact of curcumin dosing on selective biomarker changes associated with conversion to AD to establish whether there is sufficient rationale for larger prevention trials (ADCS or VA). This study also develops a new paradigm for assessing the effects of physical activity on AD risk. Both interventions may be more broadly applied to other medical conditions that are prevalent in the larger VA population such as TBI and PTSD. This proposal complements existing longitudinal studies at UCLA that examine biochemical and imaging biomarkers in untreated MCI subjects relative to progressive cognitive decline.

描述（由申请人提供）：这项为期12个月的随机双盲安慰剂控制的早期认知障碍的老年人（MCI）试图研究姜黄素在预防阿尔茨海默氏病（AD）方面的作用。 MCI通常代表初期AD，因为MCI中的潜在AD神经病理学很常见。在研究的前6个月中，我们将评估姜黄素对基于血液的生物标志物，脑葡萄糖代谢以及可预测AD风险的认知和功能参数的影响。临床前数据表明，姜黄素通过其抗氧化剂，抗炎和抗TAU/A骨料活性来实现AD发病机理的早期和晚期。先前对AD中姜黄素的研究受到较差的摄取限制，但是我们将使用一种新型的姜黄素配方来实现先前确定的靶姜黄素血液水平，从而支持向大脑递送。在本研究的第二个6个月中，我们将评估姜黄素治疗和有氧运动之间在我们的生物标志物和AD风险临床指数上进行协同作用的潜力。运动改善了认知的某些方面，并增加了大脑中的IGF-1和BDNF水平。这些作用可能会通过姜黄素潜能，除其他作用外，还可以降低胰岛素/神经营养因子抗性。一般设计：我们将研究补充12个月的姜黄素补充剂对在UCLA和ADNI MCI队列中鉴定出的等离子生物标志物的影响，以指示AD风险。血浆将在0、6和12个月收集。其他终点包括0、6和12个月的神经心理学，行为和功能评估以及0和6个月时FDG-PET脑成像。由于体育活动水平可以独立调节向AD的发展速率，因此试验的后半部分将评估来自Aerobi运动富集计划的潜在添加效益。我们选择了瑜伽，而不是典型的跑步机运动，因为它既包括抗药性训练，又包括特定序列中的有氧训练，可以帮助维持注意力并减少损耗。标准的瑜伽序列（Sun Salutations）等同于中度有氧运动，瑜伽研究的辍学率低于其他可比运动试验。在有氧瑜伽类中，通过一个月的培训，讲师将提高实践强度，以确保目标心率（最大心率的60-80％）满足，并且受试者在开始冷静序列之前出汗。非野性瑜伽群体控制着潜在的混杂，例如社交互动和积极参与，并可能改善生活质量和抑郁症的指标（与基线相比），但不可能提供足够的运动来改善生物标志物或与MCI相关的临床指数。目的：具体目的是确定补充12个月的姜黄素对AD，脑葡萄糖代谢的潜在等离子体生物标志物的影响，以及具有MCI的老年退伍军人的认知，行为和功能终点（AIM 1）（AIM 1），并确定有氧运动计划的添加是否可以进一步潜在的姜黄素补充（目标2）。假设：我们假设补充姜黄素将在6个月时改善脑葡萄糖代谢，在6个月和12个月时改变基于血液的AD风险的血液生物标志物，并在12个月时改善认知，行为和功能性终点。我们进一步假设，相对于其他治疗组，在姜黄素 +有氧瑜伽治疗组中将看到更实质性的生物标志物和临床改善。潜在结果：这项工作将有助于评估姜黄素剂量对与AD转化相关的选择性生物标志物变化的影响，以确定是否有足够的预防试验（ADC或VA）的基本原理。这项研究还开发了一种新的范式来评估体育活动对AD风险的影响。两种干预措施都可以更广泛地应用于在TBI和PTSD等较大的VA人群中普遍存在的其他医疗状况。该提案完成了UCLA的现有纵向研究，该研究研究了相对于渐进认知能力下降的未经处理的MCI受试者的生化和成像生物标志物。