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: 8100498
• 负责人: DONALD W BOWDEN
• 金额: $ 64.85万
• 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/8100498
• 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; 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; Recruitment Activity; Retinal Diseases; Risk; Risk Factors; Sampling Studies; Severities; Testing; Vascular Dementia; Vascular Diseases; 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的危险因素。来自人群的数据表明，糖尿病的几种合并症增加了认知障碍、与痴呆相关的脑结构变化（如磁共振成像（MRI）测量）和痴呆的风险。脑血管疾病和认知之间的关系，特别是在糖尿病仍然研究不足，了解甚少。脑血管疾病引起的痴呆通常被称为“血管性痴呆”或血管性认知障碍（VCI）。尽管VCI的患病率很高，但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远不如阿尔茨海默病研究。VCI的一个显著特征是，迄今为止，仅根据医学诊断难以预测风险。我们假设遗传因素是2型糖尿病家族中脑血管疾病和相关认知功能障碍的重要因素。此外，这些遗传因素的大小可以测量，它们与环境影响的相互作用可以量化，有助于这些性状的基因的染色体位置可以映射。这些假设将在糖尿病心脏研究（DHS）样本中进行测试，这是一个广泛表征的家庭集合，通过从先前参与DHS的500个家庭中招募1200名受试者进行认知测试和MRI脑部扫描。将评价MRI测量值（白色病变评分、弥散各向异性指数、平均白色灌注、总脑体积、总白色体积、总灰质体积）、认知能力和DHS提供的广泛临床测量值之间的关系，以确定脑血管疾病和认知能力的相关性。将估计认知和MRI测量的遗传成分，并使用来自DHS的预先存在的基因组扫描数据进行全面的遗传分析，以绘制包含有助于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族中脑血管疾病和认知障碍的MRI衍生指标的遗传学研究。这项研究的成功完成将创建一个独特的信息数据库，并提供对这些疾病的遗传和生活方式贡献者的见解。