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

• 批准号: 8246523
• 负责人: Caterina Rosano
• 金额: $ 53.76万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-07 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8246523
• 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; 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

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.

描述（由申请人提供）：随着1型糖尿病（T1D）的成年人的寿命更长，除了多个微型和宏观血管并发症外，它们越来越有可能发展出脑异常。这些大脑特征与在老年人中观察到的特征非常相似，不应被视为良性。与年龄相关的大脑变化相似，T1D中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。我们建议量化大量具有T1D的中年成年人的性质，严重性和风险因素。我们将使用尖端的成像技术来测量在常规脑磁性共振成像（MRI）上看不见的神经激活，血流和微结构异常。我们的初步结果表明，T1D中的脑萎缩和较低的脑血流位于额叶和皮层下区域内。因此，我们假设患有T1D的中年成年人在额叶和皮层下区域内加速了大脑衰老，并连接区域，并且T1D特异性因素和并发症的累积暴露和严重性可以解释局灶性大脑衰老的负担。我们建议从正在进行的糖尿病并发症的纵向流行病学（EDC）队列研究（平均年龄[SD]：48 [7.6]，50％女性，95％白人）的参与者那里获得190个脑磁性共振成像（MRI）。与两组非糖尿病成年人（n = 96）和年龄较大（n = 167）的现有数据相比，大脑MRI数据将为a）； b）与EDC直接确定了22年的糖尿病风险因素和并发症有关； c）与处理速度的度量相关的检查。该项目的结果将是EDC队列中未来研究的垫脚石，以检查脑损伤和认知能力下降速度的进展。这项研究的结果还有可能阐明2型糖尿病中脑变性的机制。在2009年EDC队列的资助数据收集阶段中，该提案是唯一的定时时间。我们的项目经过战略性设计，旨在在四年内完成工作范围。该项目将使用现有的招聘基础设施，这是一个大脑MRI中心，扫描仪致力于研究新数据，由研究人员和研究人员组成的团队和研究人员具有多学科的先前合作，在22年中收集了糖尿病的纵向数据。 公共卫生相关性：1型糖尿病患者（T1D）的大脑变化很常见，它们与老年人观察到的异常非常相似。我们建议表征T1D（脑灌注，神经激活和微结构水平）中加速大脑衰老的性质，并识别其决定因素。