Action for Health in Diabetes Brain Magnetic Resonance Imaging Ancillary Study

描述(由申请人提供)：在成人2型糖尿病患者的护理中，保护大脑健康是一个重要的目标，他们面临着更高的萎缩、脑血管疾病和认知障碍的风险。减肥和增加体力活动有望成为达到这一目的的潜在有效策略，但目前尚未在任何人群中得到证实。因为意外的体重减轻往往先于晚年大脑健康的下降，所以有必要进行随机对照临床试验，该试验必须以有效的行为干预为特色，并在一个具有良好特征的大型队列中长期持续。安装这样一个从头开始的计划将是非常昂贵的。相反，我们建议利用正在进行的非常成功的糖尿病健康行动(Look Ahead)随机对照临床试验，将横断面磁共振成像(MRI)添加到其广泛的数据收集方案中。这是可行的：临床试验的参与者一再被证明愿意加入脑成像研究，我们已经制定了成功的方案来维护安全性、保密性和质量。这是新颖的：展望未来，我们提出的最先进的磁共振成像方案提供了一个前所未有的机会，来评估中年行为变化对大脑结构和功能的长期有效性，并促进对糖尿病患者大脑健康的了解。我们以经济高效的方式为快速增长和未得到充分研究的美国人口群体解决一个重要的公共卫生优先事项，利用Look Forward提供的广泛研究资源。我们响应PAR-09-247，它的目标是将辅助研究应用于主要的NIDDK临床试验，包括展望未来。我们将从3家前瞻性诊所招募496名年龄在55-85岁之间的2型糖尿病患者。他们将在10年前肥胖或超重的时候被随机分配，概率相等，要么进行持续的高强度生活方式干预，导致持续的体重减轻，要么增加体力活动，要么控制条件(糖尿病支持和教育)，促进良好的保持能力。一个经过验证的标准化结构MRI方案将提供局部脑和缺血病变体积；功能MRI将提供对功能激活、静息状态连接和脑血流的评估。将进行经过测试的认知电池和体力活动评估。对这些数据的全面分析将利用既定的统计方法和新颖的机器学习方法。展望未来提供了参与者10年来的健康和行为、他们的医疗保健及其成本、试验干预的广泛特征；最先进的数据管理系统；以及开发公共访问数据库的规定。我们的研究团队包括脑成像、糖尿病研究、行为医学、数据和图像分析、神经流行病学和协作方面的资深和富有成效的专家。

DESCRIPTION (provided by applicant): Preservation of brain health is a critical goal in the care of adults with type 2 diabetes mellitus, who are at increased risk for atrophy, cerebrovascular disease, and cognitive impairment. Weight loss and increased physical activity hold promise as potentially effective strategies for this purpose, but are currently unproven in any population. Because unintended weight loss often precedes declines in later life brain health, a randomized controlled clinical trial is necessary, which must feature an effective behavioral intervention that is sustained over a long period of time in a large well characterized cohort. Mounting such a program de novo would be very expensive. Instead, we propose to make use of the ongoing and very successful Action for Health in Diabetes (Look AHEAD) randomized controlled clinical trial, adding cross-sectional magnetic resonance imaging (MRI) to its extensive data collection protocol. This is feasible: participants in clinical trials have been repeatedly shown to be willing to join brain imaging studies and we have developed successful protocols for maintaining safety, confidentiality, and quality. This is novel: Look AHEAD and the state-of-the-art MRI protocols that we propose provide an unprecedented opportunity to assess the long-term effectiveness of mid-life behavioral changes on brain structure and function and to advance understanding of brain health in diabetes. We address an important public health priority for a rapidly growing and under-studied segment of the US population in a cost-effective manner, leveraging the extensive research resources available from Look AHEAD. We respond to PAR-09-247, which targets ancillary study applications to major NIDDK clinical trials, including Look AHEAD. We will enroll 496 participants, ages 55-85 years with type 2 diabetes, from 3 Look AHEAD clinics. They will have been randomly assigned 10 years ago when they were obese or overweight, with equal probability, to either an ongoing intensive lifestyle intervention that has induced sustained weight loss and increased physical activity or control condition (diabetes support and education) that has fostered excellent retention. A proven protocol for standardized structural MRI will provide regional brain and ischemic lesion volumes; functional MRI will provide assessments of functional activation, resting state connectivity, and cerebral blood flow. A tested cognitive battery and physical activity assessment will be administered. A comprehensive analysis of these data will make use of established statistical approaches and novel machine-learning methods. Look AHEAD provides extensive 10-year characterizations of participant's health and behavior, their medical care and its cost, and the trial's interventions; state-of-the art data management systems; and provisions for developing public access databases. Our research team includes established and productive experts in brain imaging, diabetes research, behavioral medicine, data and image analysis, neuroepidemiology, and collaboration.