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）：根据谁的“糖尿病流行”。仅在美国，2007年的糖尿病成本估计为1740亿美元。这笔费用的大部分是由于2型糖尿病伴随的许多问题，包括血管疾病和认知障碍的风险增加，这可能会限制日常生活的活动以及患者遵守治疗的能力。然而，关于遗传学，环境和糖尿病相关因素（例如血管疾病）对心血管，遗传，流行病学以及对糖尿病富集人群中1200名受试者的最先天性脑成像方法的相对贡献，鲜血疾病的相对贡献知之甚少。该提案具有三个特定的目标，可以将申请人的神经科学背景与导师的广泛流行病学和遗传经验相结合：1）确定在使用功能MRI的工作记忆任务中与T2DM相关的大脑区域； 2） 评估预定义区域内MRI措施之间的流行病学关系和 认知，脑血管健康，身体特征和广泛获得的心血管疾病措施的度量； 3）执行遗传力和单核苷酸多态性（SNP）关联分析。受试者将从先前对糖尿病和心血管疾病的研究中招募，其中获取广泛的遗传和心血管措施，并将完成认知测试电池，临床测试（例如空腹血糖）以及MR成像扫描，并允许评估白质完整性，脑灌注，大脑体积，脑体积和神经活动。通过fMRI数据进行素分析的整个大脑分析；广义估计方程将用于模拟MR来源数据，心血管和临床指标，身体特征和认知之间的流行病学关系。在流行病学分析中确定的特征的影响，将估计功能性MRI测量的遗传力。从先前的DNA分析得出的广泛遗传数据库将用于评估MRI性状的单核苷酸多态性关联。在全球范围内和美国，糖尿病已达到流行比例。这项研究旨在整合技术认知，成像和遗传学技术的状态，以了解有关为什么2型糖尿病会增加认知障碍的风险的更多信息。该信息对于确定糖尿病相关认知能力下降，设计有效治疗并为预防策略提供的生物学原因很重要。