MRI, GENETIC AND COGNITIVE PRECURSORS OF AD AND DEMENTIA

我们将把阿尔茨海默病(AD)和痴呆的危险因素联系起来 在Framingham子代队列中和磁共振成像 (MRI)和认知表现测量。前瞻性流行病学 对原始弗雷明翰队列的研究已经进行了50年。 自1976年以来，在这个队列中对痴呆症进行了研究，共有235例病例 确定；这些符合AD的标准中有58%。他们的 儿童，弗雷明翰的后代，已经被前瞻性地研究了 26年了。在此期间，与AD相关的大量风险因素数据 和痴呆症，包括：亲代AD，apoE基因， 高血压、中风、中风危险因素、绝经后雌激素 治疗、非类固醇消炎药、教育和香烟 抽烟。简而言之，大量有价值的前瞻性收集的数据 可用于后代，例如59个是apoE 4/4纯合子 681例为apoE 3/4杂合子。 将对3000人进行神经心理测试 后代，复制22年前给他们的电池 年龄相仿的父母。脑白质的定量MRI研究 变化、静止性中风和脑萎缩将与痴呆症风险相关 因素和认知表现。我们假设 通过MRI扫描和神经心理测试检测到的异常将是 在有痴呆症危险因素的参与者中增加。特别的 感兴趣的是探索为什么一些载脂蛋白E4携带者逃脱痴呆症 并考察了风险因素与认知能力的相互作用 减损。 我们将研究阿尔茨海默病和痴呆症的遗传风险。DNA已经被 从父母和子女身上收集的。高密度基因组扫描 已经为弗雷明翰家庭的样本进行了表演，并将很快 其余部分完成。我们将进行遗传连锁分析 用于核磁共振和认知表现测量，以识别区域 包含阿尔茨海默病和痴呆症易感基因的基因组。

We will relate risk factors for Alzheimer's Disease (AD) and dementia in the Framingham Offspring cohort and to Magnetic Resonance Imaging (MRI) and cognitive performance measures. Prospective epidemiological study of the Original Framingham cohort has been under way for 50 years. Dementia has been studied in this cohort since 1976, with 235 cases identified; 58 percent of these fulfilling criteria for AD. Their children, the Framingham Offspring, have been studied prospectively for 26 years. During this time, extensive risk factor data pertinent to AD and dementia have been collected, including: parental AD, apoE genotype, hypertension, stroke, stroke risk factors, post-menopausal estrogen therapy, nonsteroidal antiinflamatory drugs, education, and cigarette smoking. In short, a wealth of valuable prospectively collected data are available for the Offspring, e.g., 59 are apoE 4/4 homozygotes and 681 are apoE 3/4 heterozygotes. A neuropsychological test battery will be administered to the 3,000 Offspring, replicating the battery administered 22 years ago to their parents at a similar age. Quantitative MRI studies of white matter change, silent stroke and brain atrophy will be related to dementia risk factors and to cognitive performance. We hypothesize that the abnormalities detected by MRI scan and neuropsychological tests will be increased among participants with dementia risk factors. Of particular interest is the exploration of why some apoE4 carriers escape dementia and an examination of the interaction of risk factors with cognitive impairment. We will examine the genetic risk for AD and dementia. DNA has been collected on both the parents and offspring. A high density genome scan has been performed for a sample Framingham families and will soon be completed in the remainder. We will perform genetic linkage analyses for MRI and cognitive performance measures in order to identify regions of the genome containing genes predisposing to AD and dementia.