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Frachial Offspring队列和磁共振成像 (MRI)和认知表现指标。前瞻性流行病学 对原始Fragrance队列的研究已经进行了50年。 自1976年以来，对痴呆症进行了研究，共有235例 确定; 58%符合AD标准。 他们的 孩子们，Fragmentary Offspring，已经进行了前瞻性研究， 26年 在此期间，与AD相关的广泛风险因素数据 和痴呆症，包括：父母AD，apoE基因型， 高血压，脑卒中，脑卒中危险因素，绝经后雌激素 治疗、非甾体抗炎药、教育和香烟 smoking. 简而言之，大量有价值的前瞻性收集数据 可供后代使用，例如，59例为apoE 4/4纯合子， 681例为apoE 3/4杂合子。 将对这3000人进行神经心理测试 后代，复制电池管理22年前，他们的 父母年龄相仿。 白色物质的定量MRI研究 变化，无症状中风和脑萎缩将与痴呆症的风险 因素和认知表现。我们假设 通过MRI扫描和神经心理学测试发现的异常将被 在有痴呆症风险因素的参与者中增加。 特别 人们感兴趣的是探索为什么一些apoE 4携带者能逃脱痴呆症 以及对风险因素与认知功能的相互作用的研究 损伤 我们将研究AD和痴呆症的遗传风险。 DNA已经被 父母和子女身上都有。 高密度基因组扫描 已经进行了一个样本Fragmentary家庭，并将很快 在剩余部分完成。 我们将进行遗传连锁分析 用于MRI和认知性能测量， 含有易患AD和痴呆症的基因的基因组。

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.