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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(申请人提供)：由于成年1型糖尿病(T1D)患者寿命较长，他们除了出现多种微血管和大血管并发症外，还越来越有可能出现脑部异常。这些大脑特征与在老年人身上观察到的惊人相似，不应被认为是良性的。与已知的与年龄相关的脑变化类似，T1D脑异常的潜在机制包括高血糖和胰岛素功能障碍引起的继发性血管损伤。我们建议对一大群患有T1D的中年成年人的脑部异常的性质、严重性和危险因素进行量化。我们将使用尖端成像技术来测量神经激活、血流和微结构异常，这些在传统的脑磁化磁共振成像(MRI)中是看不到的。我们的初步结果表明，T1D的脑萎缩和脑血流降低局限于额顶叶和皮质下区域。因此，我们假设患有T1D的中年成年人在额顶和皮质下区域以及连接束内加速了脑老化，T1D特定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。我们建议从正在进行的糖尿病并发症纵向流行病学(EDC)队列研究的参与者(平均年龄：48[SD]：48[7.6]，50%女性，95%白人)中获取190个脑磁化磁共振成像(MRI)，这些参与者从1989年到目前为止一直被跟踪。脑部核磁共振数据将a)与两组年龄相近(n=96)和年龄较大(n=167)的非糖尿病成年人的现有数据进行比较；b)与在EDC中22年来直接确定的糖尿病风险因素和并发症有关；c)根据处理速度的测量进行检查。该项目的结果将成为EDC队列中未来研究的垫脚石，以检查大脑损伤的进展和认知功能减退率。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。这项提议的时间安排得天独厚，是为了在2009年开始的EDC队列的资助数据收集阶段收集重要信息。我们的项目经过战略设计，将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，一个配备扫描仪的脑MRI中心，用于研究收集新数据，一个研究人员和调查人员团队，他们拥有以前在神经流行病学和成像领域的多学科合作记录，以及22年来收集的关于糖尿病并发症的现有纵向数据。