Genetic Epidemiology of Cerebrovascular Disease and Cognition in Diabetes

脑血管疾病的遗传流行病学与糖尿病认知

• 批准号: 7383274
• 负责人: DONALD W BOWDEN
• 金额: $ 57.24万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7383274
• 关键词: Age; Alzheimer' s Disease; Amyloid; Biological; Blood Pressure; Blood Vessels; Body Size; Brain; Brain scan; Candidate Disease Gene; Cerebral Infarction; Cerebrovascular Disorders; Clinical; Cognition; Cognitive; Collection; Comorbidity; Condition; Coronary heart disease; Data; Data Collection; Databases; Dementia; Diabetes Mellitus; Diabetic Angiopathies; Diagnosis; Diet; Disease; Employee Strikes; Epidemic; Family; Foundations; Future; Gender; Genes; Genetic; Genome Scan; Genotype; Goals; Health system; Heart; High Prevalence; Human Genome; Impaired cognition; Investigation; Kidney Diseases; Lesion; Life Style; Location; Magnetic Resonance Imaging; Maps; Measures; Medical; Medical History; Neurofibrillary Tangles; Non-Insulin-Dependent Diabetes Mellitus; Other Genetics; Pacemakers; Participant; Pathology; Perfusion; Peripheral Nervous System Diseases; Persons; Physical activity; Population; Prevalence; Public Health; Range; Recruitment Activity; Retinal Diseases; Risk; Risk Factors; Sampling Studies; Score; Severities; Testing; Vascular Dementia; Work; base; brain volume; cognitive function; cognitive impairment no dementia; diffusion anisotropy; genetic analysis; genetic epidemiology; gray matter; indexing; insight; mild neurocognitive impairment; trait; white matter

DESCRIPTION (provided by applicant): Diabetes is a risk factor for cerebrovascular disease, cognitive impairment, and related dementia. Data derived from populations suggest that several comorbidities of diabetes increase the risk for cognitive impairment, structural brain changes associated with dementia as measured with magnetic resonance imaging (MRI), and dementia. The relationship between cerebrovascular disease and cognition, especially in diabetes remains understudied and poorly understood. Dementia due to cerebrovascular disease is often referred to as vascular dementia" or vascular cognitive impairment (VCI). Despite the high prevalence of VCI, the biological basis of this disease and its relationship with structural brain changes measured with MRI has been far less studied than Alzheimer's disease. A striking feature of VCI is that risk to date has been difficult to predict based on medical diagnosis alone. We hypothesize genetic factors are significant contributors to cerebrovascular disease and associated cognitive impairment in families enriched for type 2 diabetes. Further, the magnitude of these genetic factors can be measured, their interaction with environmental influences can be quantitated, and the chromosomal location of genes contributing to these traits can be mapped. These hypotheses will be tested in the Diabetes Heart Study (DHS) sample, an extensively characterized collection of families, by recruiting 1200 subjects from 500 families that previously participated in the DHS who will undergo cognitive testing and MRI brain scans. The relationships between MRI measures (white matter lesion score, diffusion anisotropy index, mean white matter perfusion, total brain volume, total white matter volume, total gray matter volume), cognitive ability, and extensive clinical measures available from the DHS will be evaluated to identify correlates of cerebrovascular disease and cognitive ability. The heritable component of cognition and MRI measures will be estimated and a comprehensive genetic analysis will be performed using preexisting genome scan data from the DHS to map regions that contain genes contributing to cognition and cerebrovascular disease. These studies will create unique data collection for genetic and other studies of cerebrovascular disease and cognition. This is a study of the genetics of MRI-derived measures of cerebrovascular disease and cognitive impairment in diabetes families. Successful completion of the study will create a unique database of information and provide insights into the genetic and lifestyle contributors to these disorders.

描述(由申请人提供)： 糖尿病是脑血管疾病、认知障碍和相关痴呆症的危险因素。来自人群的数据表明，几种糖尿病的共病会增加认知障碍、磁共振成像(MRI)测量的与痴呆症相关的结构性脑变化以及痴呆症的风险。脑血管疾病和认知之间的关系，特别是在糖尿病患者中的关系，仍然没有得到充分的研究和了解。脑血管疾病引起的痴呆通常被称为“血管性痴呆”或血管认知障碍(VCI)。尽管VCI的发病率很高，但与阿尔茨海默病相比，人们对这种疾病的生物学基础及其与MRI测量的脑结构变化的关系的研究要少得多。VCI的一个显著特点是，到目前为止，仅凭医学诊断很难预测风险。我们假设遗传因素是2型糖尿病家族性脑血管疾病和相关认知障碍的重要因素。此外，可以测量这些遗传因素的大小，可以量化它们与环境影响的交互作用，可以绘制导致这些特征的基因的染色体位置。这些假设将在糖尿病心脏研究(DHS)样本中得到验证，DHS样本是一个具有广泛特征的家庭集合，通过从500个以前参与DHS的家庭招募1200名受试者，这些受试者将接受认知测试和核磁共振脑部扫描。将评估MRI指标(白质病变评分、扩散各向异性指数、平均白质灌注量、总脑体积、总白质体积、总灰质体积)、认知能力和国土安全部提供的广泛临床指标之间的关系，以确定脑血管疾病和认知能力的相关性。将估计认知和核磁共振测量的可遗传成分，并将使用国土安全部现有的基因组扫描数据进行全面的遗传分析，以绘制包含导致认知和脑血管疾病的基因的区域。这些研究将为脑血管疾病和认知的遗传学和其他研究创造独特的数据收集。这是一项关于糖尿病家庭中脑血管疾病和认知障碍的MRI测量的遗传学研究。这项研究的成功完成将创建一个独特的信息数据库，并为这些疾病的遗传和生活方式提供洞察力。