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: 8033157
• 负责人: CHRISTINA E HUGENSCHMIDT
• 金额: $ 5.58万
• 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/8033157
• 关键词: Accounting; Activities of Daily Living; Affect; Age; Aging; Area; 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; 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; United States National Institutes of Health; Variant; Vascular Diseases; brain volume; cerebrovascular; cognitive change; cost; design; diabetic; effective therapy; epidemiological model; executive function; experience; genetic analysis; 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，全球范围内存在“糖尿病流行”。仅在美国，2007 年糖尿病造成的损失就估计达到 1,740 亿美元。其中大部分费用是由于 2 型糖尿病伴随的许多问题造成的，包括血管疾病和认知障碍风险增加，这可能会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（例如血管疾病）对心血管、遗传、流行病学和针对糖尿病人群中 1200 名受试者的最先进的脑成像方法的相对贡献知之甚少。该提案具有三个具体目标，将申请人的神经科学背景与导师丰富的流行病学和遗传学经验相结合：1）使用功能性 MRI 识别工作记忆任务期间与 T2DM 相关的大脑区域； 2） 评估预定义感兴趣区域内 MRI 测量值之间的流行病学关系 认知、脑血管健康、身体特征以及先前获得的心血管疾病的广泛测量指标； 3) 进行遗传力和单核苷酸多态性 (SNP) 关联分析。受试者将从之前的糖尿病和心血管疾病研究中招募，其中获得了广泛的遗传和心血管测量数据，并将完成一系列认知测试、临床测试（例如空腹血糖）和 MR 成像扫描，以评估白质完整性、脑灌注、脑容量和神经活动。将对功能磁共振成像数据进行体素全脑分析；广义估计方程将用于模拟 MR 衍生数据、心血管和临床测量、身体特征和认知之间的流行病学关系；将考虑流行病学分析中确定的特征的影响来估计功能性 MRI 测量的遗传力。来自先前 DNA 分析的广泛遗传数据库将用于评估 MRI 特征的单核苷酸多态性关联。在全球和美国，糖尿病已达到流行病的程度。这项研究旨在整合最先进的认知、成像和遗传学技术，以更多地了解为什么 2 型糖尿病会增加认知障碍的风险。这些信息对于确定糖尿病相关认知能力下降的生物学原因、设计有效的治疗方法和为预防策略提供信息非常重要。

项目成果

A network of genes, genetic disorders, and brain areas.

• DOI: 10.1371/journal.pone.0020907
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Hayasaka S;Hugenschmidt CE;Laurienti PJ
• 通讯作者: Laurienti PJ

A link between type 2 diabetes and brain function.

2 型糖尿病与大脑功能之间的联系。

• DOI: 10.1097/01.jaa.0000437750.76865.61
• 发表时间: 2013
• 期刊: JAAPA : official journal of the American Academy of Physician Assistants
• 作者: Hugenschmidt,ChristinaE

Cerebral structural changes in diabetic kidney disease: African American-Diabetes Heart Study MIND.

• DOI: 10.2337/dc14-1231
• 发表时间: 2015-02
• 期刊: Diabetes care
• 影响因子: 16.2
• 作者: Sink KM;Divers J;Whitlow CT;Palmer ND;Smith SC;Xu J;Hugenschmidt CE;Wagner BC;Williamson JD;Bowden DW;Maldjian JA;Freedman BI
• 通讯作者: Freedman BI