Genetic and imaging analysis of cerebrovascular disease and cognition in diabetes

糖尿病脑血管疾病与认知的遗传和影像学分析

• 批准号: 7758234
• 负责人: CHRISTINA E HUGENSCHMIDT
• 金额: $ 5.21万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-14 至 2012-01-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7758234
• 关键词: Accounting; Activities of Daily Living; Affect; Age; Aging; Area; Arts; Back; Biological; Blood Glucose; Blood Vessels; Brain; Brain Pathology; Brain imaging; Brain region; Cardiovascular Diseases; Cardiovascular system; Cerebrovascular Disorders; Cerebrum; Characteristics; Clinical; Clinical Markers; Cognition; Cognitive; DNA analysis; Data; Deterioration; Diabetes Mellitus; Disease; Disease Marker; Environment; Epidemic; Epidemiology; Equation; Evaluation; Exhibits; Fasting; Fellowship; Foundations; Functional Magnetic Resonance Imaging; Funding; Gender; Genes; Genetic; Genetic Databases; Genetic Techniques; Glycosylated hemoglobin A; Health; Heritability; Image; Image Analysis; Impaired cognition; Incidence; Knowledge; Learning; MRI Scans; Magnetic Resonance Imaging; Measures; Mediating; Memory; Mentors; Metric; Mind; Modeling; Neurosciences; Non-Insulin-Dependent Diabetes Mellitus; Parents; Patients; Perfusion; Physical Function; Population; Recruitment Activity; Relative (related person); Resources; Risk; Risk Factors; Scanning; Short-Term Memory; Single Nucleotide Polymorphism; Structure; Testing; United States; Variant; Vascular Diseases; brain volume; cerebrovascular; cognitive change; cost; design; diabetic; effective therapy; epidemiological model; executive function; experience; genetic linkage analysis; genome wide association study; genome-wide linkage; imaging modality; interest; normal aging; parent grant; physical conditioning; relating to nervous system; therapy development; trait; white matter

DESCRIPTION (provided by applicant): According to the WHO there is a global "diabetes epidemic." In the United States alone, the cost of diabetes in 2007 was estimated at $174 billion. Much of this expense is due to the many problems that accompany type 2 diabetes, including vascular disease and increased risk for cognitive impairments, which may limit activities of daily living and the patients' ability to comply with treatments. However, little is known about the relative contributions of genetics, environment, and diabetes-associated factors such as vascular disease to cardiovascular, genetic, epidemiological, and state of the art brain imaging methods for 1200 subjects in a diabetes-enriched population. The proposal has three specific aims that combine the applicant's neuroscience background with the mentor's extensive epidemiological and genetic experience: 1) Identify brain regions that exhibit an association with T2DM during a working memory task using functional MRI; 2) Assess epidemiological relationships between MRI measures within pre-defined regions of interest and measures of cognition, cerebrovascular health, physical characteristics, and extensive previously acquired measures of cardiovascular disease; 3) Perform heritability and single nucleotide polymorphism (SNP) association analyses. Subjects will be recruited from a previous study of diabetes and cardiovascular disease where extensive genetic and cardiovascular measures were acquired and will complete a cognitive test battery, clinical tests (e.g., fasting blood glucose), and MR imaging scans that will allow assessment of white matter integrity, cerebral perfusion, brain volume, and neural activity. Voxel-wise whole brain analyses will be performed on the fMRI data; generalized estimating equations will be used to model epidemiological relationships between MR-derived data, cardiovascular and clinical measures, physical characteristics, and cognition; and the heritability of functional MRI measures will be estimated taking into account the influence of characteristics identified in the epidemiological analysis. The extensive genetic database derived from prior DNA analysis will be used to assess single nucleotide polymorphism association of MRI traits. Globally and in the US, diabetes has reached epidemic proportions. This study aims to integrate state of the art cognitive, imaging, and genetics techniques to learn more about why type 2 diabetes increases the risk for cognitive impairments. This information is important to establish the biological causes for diabetesrelated cognitive decline, design effective treatments and inform preventative strategies.

描述（由申请人提供）：根据世界卫生组织的说法，全球存在“糖尿病流行病”。仅在美国，2007年治疗糖尿病的费用估计为1740亿美元。大部分费用是由于伴随2型糖尿病的许多问题，包括血管疾病和认知障碍的风险增加，这可能限制日常生活活动和患者遵守治疗的能力。然而，对于遗传、环境和糖尿病相关因素（如血管疾病）对心血管、遗传、流行病学和1200名糖尿病富集人群的脑成像方法的相对贡献知之甚少。该提案有三个具体目标，将申请人的神经科学背景与导师广泛的流行病学和遗传学经验结合起来：1)在工作记忆任务中使用功能性MRI识别与T2DM相关的大脑区域；2）