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Imaging biomarkers of accelerated brain aging in Type-1 Diabetes

1 型糖尿病大脑加速老化的成像生物标志物

基本信息

批准号：
8444575
负责人：
Caterina Rosano
金额：
$ 50.4万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-07 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8444575
关键词：
Adult Age Anastomosis - action Atrophic Behavioral Benign Biological Markers Blood Vessels Blood flow Brain Brain Injuries Brain region Calculi Cardiovascular system Cell membrane Cerebrovascular Circulation Cerebrum Characteristics Cohort Studies Collaborations Complications of Diabetes Mellitus Contralateral Creatinine Data Data Collection Dementia Diabetes Mellitus Diffuse Disease Dose Elderly Employee Strikes Epidemiologic Studies Epidemiology Event Exercise Exposure to Functional disorder Funding Future Hyperglycemia Hyperlipidemia Hypertension Image Imaging technology Impaired cognition Insulin Insulin-Dependent Diabetes Mellitus Insulin-Like Growth Factor Receptor Left Life Lipids Longevity Magnetic Resonance Imaging Measurement Measures Morbidity - disease rate National Institute of Diabetes and Digestive and Kidney Diseases Nature Non-Insulin-Dependent Diabetes Mellitus Parietal Participant Pathology Patient Care Patients Pattern Perfusion Peripheral Nervous System Diseases Persons Pharmaceutical Preparations Phase Pilot Projects Public Health Research Research Design Research Infrastructure Research Personnel Retinal Diseases Risk Risk Factors Secondary to Severities Smoking Spatial Distribution Speed Staging Structure Time Vascularization Woman Work age related aging brain base blood perfusion cardiovascular risk factor cerebral atrophy cohort cost density design diabetes risk diabetic disability experience fasting glucose functional decline gray matter middle age mortality multidisciplinary neuroimaging neuropsychological non-diabetic processing speed public health relevance relating to nervous system white matter

项目摘要

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.

描述（由申请人提供）：随着患有 1 型糖尿病 (T1D) 的成年人寿命延长，除了多种微血管和大血管并发症外，他们也越来越容易出现大脑异常。这些大脑特征与老年人中观察到的特征惊人相似，不应被视为良性。与已知的与年龄相关的大脑变化类似，T1D 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。我们建议量化一大群中年 T1D 患者大脑异常的性质、严重程度和危险因素。我们将使用尖端成像技术来测量传统脑磁化共振成像 (MRI) 上看不到的神经激活、血流和微结构异常。我们的初步结果表明，T1D 患者的脑萎缩和脑血流量降低集中在额顶叶和皮质下区域。因此，我们假设患有 T1D 的中年人加速了额顶叶和皮质下区域以及连接束的大脑老化，并且 T1D 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大脑老化的负担。我们建议从正在进行的糖尿病并发症流行病学 (EDC) 队列研究（平均年龄 [SD]：48 [7.6]，50% 女性，95% 白人）的参与者中获取 190 名脑磁化共振成像 (MRI)，这些参与者从 1989 年至今一直被跟踪。脑 MRI 数据将 a) 与年龄相近 (n=96) 和年龄较大 (N=167) 的两组非糖尿病成年人的现有数据进行比较； b) 与 EDC 22 年来直接确定的糖尿病危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 EDC 队列未来研究的基石，以检查脑损伤的进展和认知能力下降的速度。这项研究的结果还有可能阐明 2 型糖尿病脑退化的机制。该提案的时机非常独特，旨在从 2009 年开始的 EDC 队列资助数据收集阶段捕获重要信息。我们的项目经过战略设计，旨在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、配备专门用于研究收集新数据的扫描仪的脑部 MRI 中心、具有神经流行病学和影像学多学科先前合作记录的研究人员和研究人员团队，以及 22 年来收集的糖尿病并发症的现有纵向数据。