Imaging biomarkers of accelerated brain aging in Type-1 Diabetes

描述（由申请人提供）：随着1型糖尿病（T1 D）成年人的寿命延长，他们越来越有可能发展出大脑异常，以及多种微血管和大血管并发症。这些大脑特征与在老年人中观察到的特征惊人地相似，不应被视为良性。与已知的年龄相关的大脑变化相似，T1 D大脑异常的潜在机制包括继发于高血糖和胰岛素功能障碍的血管损伤。我们建议量化的性质，严重程度和风险因素，在一个大组的中年成人T1 D脑异常。我们将使用尖端的成像技术来测量神经激活，血流和微结构异常，这些在传统的大脑磁化共振成像（MRI）上是不可见的。我们的初步研究结果表明，脑萎缩和脑血流量降低T1 D局限于额顶叶和皮质下区域。因此，我们假设T1 D中年人在额顶叶和皮质下区域以及连接束内加速了脑老化，并且T1 D特异性因素和并发症的累积暴露和严重程度可以解释局灶性加速脑老化的负担。我们计划从正在进行的糖尿病并发症纵向流行病学（EDC）队列研究（平均年龄[SD]：48 [7.6]，50%为女性，95%为白色）的参与者中获得190例脑磁化共振成像（MRI），这些参与者从1989年至今一直接受随访。脑MRI数据将a）与两组年龄相似（n=96）和年龄较大（N=167）的非糖尿病成人的现有数据进行比较; B）与EDC中已直接确定22年的糖尿病风险因素和并发症相关; c）检查与处理速度测量的关系。该项目的结果将成为未来EDC队列研究的垫脚石，以检查脑损伤的进展和认知能力下降的速度。这项研究的结果也有可能阐明2型糖尿病脑变性的潜在机制。该提案的时间安排独特，以在2009年开始的EDC队列的资助数据收集阶段收集重要信息。我们的项目在战略上是为了在四年内完成工作范围。该项目将使用现有的招募基础设施，一个专门用于研究的脑部MRI中心，专门用于收集新数据的扫描仪，一个研究人员和研究人员团队，他们在神经流行病学和成像方面具有多学科合作的记录，以及22年来收集的糖尿病并发症的现有纵向数据。 公共卫生相关性：大脑变化在1型糖尿病（T1 D）患者中很常见，它们与老年人中观察到的异常惊人相似。我们建议描述T1 D加速脑老化的性质（脑灌注，神经激活和微观结构水平），并确定其决定因素。

DESCRIPTION (provided by applicant): As adults with Type 1 Diabetes (T1D) live longer, they are increasingly more likely to develop brain abnormalities in addition to multiple micro- and macro-vascular complications. These brain features are strikingly similar to those observed in older adults and should not be considered benign. Similar to what is known for age-related brain changes, the potential mechanisms of brain abnormalities in T1D include vascular damage secondary to hyperglycemia and insulin dysfunction. We propose to quantify the nature, severity and risk factors re brain abnormalities in a large group of middle-aged adults with T1D. We will use cutting-edge imaging technology to measure neural activation, blood flow and micro-structural abnormalities that are not visible on conventional brain magnetization resonance imaging (MRI). Our preliminary results indicate that brain atrophy and lower cerebral blood flow in T1D are localized within fronto-parietal and subcortical regions. Therefore, we hypothesize that middle-aged adults with T1D have accelerated brain aging within the fronto-parietal and subcortical regions and connecting tracts and that cumulative exposure and severity of T1D-specific factors and complications can explain the burden of focal accelerated brain aging. We propose to obtain 190 brain magnetization resonance imaging (MRI) from participants of the ongoing longitudinal Epidemiology of Diabetes Complications (EDC) cohort study (mean age [SD]: 48 [7.6], 50% women, 95% white) who have been followed from 1989 to date. Brain MRI data will be a) compared with existing data of two groups of non diabetic adults of similar age (n=96) and of older age (N=167); b) related to diabetes-risk factors and complications that have been directly ascertained for 22 years in the EDC; c) examined in relationship with measures of processing speed. Results from this project will be the stepping stone for future studies in the EDC cohort to examine progression of brain damage and rate of cognitive decline. Results of this study also have the potential to clarify mechanisms underlying brain degeneration in Type 2 diabetes. This proposal is uniquely timed to capture important information during the funded data collection phase of the EDC cohort beginning in 2009. Our project has been strategically designed to complete the scope of work within four years. This project will use an existing recruitment infrastructure, a brain MRI center with scanners dedicated to research to collect new data, a team of research staff and investigators with track record of multidisciplinary previous collaborations in neuroepidemiology and imaging, and existing longitudinal data on diabetes complications collected over 22 years. PUBLIC HEALTH RELEVANCE: Brain changes are common in persons with Type 1 Diabetes (T1D) and they are strikingly similar to abnormalities observed in older adults. We propose to characterize the nature of accelerated brain aging in T1D (cerebral perfusion, neural activation and micro-structure level) and identify their determinants.