DEMOGRAPHIC MULTISTATE MODELING OF ALZHEIMERS DISEASE

阿尔茨海默病的人口多态建模

• 批准号: 6372321
• 负责人: DOUGLAS C EWBANK
• 金额: $ 10.68万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6372321
• 关键词: African American; Alzheimer's disease; Hispanic Americans; Japanese American; apolipoprotein E; caucasian American; clinical research; computer program /software; disease /disorder onset; disease /disorder proneness /risk; epidemiology; gender difference; gene expression; genetic susceptibility; genotype; human data; mathematical model; meta analysis; myocardial ischemia /hypoxia; racial /ethnic difference

The proposed research involves extensions of a multi-state model of Alzheimer's disease (AD) and ischemic heart disease (IHD). The model is designed to study the effects of the Apolipoprotein-E gene (APOE) on the risks of both diseases, but it can be adapted to study the effects of any fixed traits. The model has important practical and theoretical implications for both demography and epidemiology. The potential of the model has been demonstrated by fitting it to published data. The proposed research will apply the model to raw data from 40 clinical studies of the relationship between APOE and AD. These studies include 5939 cases of AD and 8746 controls. The proposal includes six applications and extensions of the model: 1) A study of sex differentials in the role of APOE in AD in populations of European origin. This will test hypotheses about the causes of the higher risk of AD among women and the reduced differential in AD risk by APOE genotype among women. 2) Use the model to project the number of cases of AD to the year 2030 by duration of disease and severity of symptoms. This will examine the potential impact of a) projected declines in IHD mortality, b) likely new treatments to slow the progression of AD, and c) likely new approaches to delaying the age at onset of AD. An important aspect of this will be to examine the impact of different assumptions about which APOE genotypes will benefit from future developments. 3) Produce a more efficient computer program to estimate the parameters of the model. The model is currently programmed in a spreadsheet program which cannot be expanded to compare more than two populations. 4) Examine differences in the effects of APOE on AD by race/ethnicity. Previous research suggests there are large differences in the relationship between APOE and AD whites, African-Americans, Hispanics, and Japanese. This research will test hypotheses about the likely differences in the etiology of AD that underlie these differences in the patterns of risk. 5) It is likely that during the next few years there will be major findings of other risk factors (especially genetic risk factors) for AD. This will complicate the process of comparing studies across populations and quantifying the importance of individual risk factors. The model of APOE and AD will be expanded to include additional risk factors.

拟议的研究涉及阿尔茨海默病（AD）和缺血性心脏病（IHD）的多状态模型的扩展。该模型旨在研究载脂蛋白-E 基因 (APOE) 对这两种疾病风险的影响，但它也可以适用于研究任何固定性状的影响。 该模型对人口学和流行病学具有重要的实践和理论意义。 该模型的潜力已通过将其拟合到已发布的数据来证明。 拟议的研究将将该模型应用于 40 项 APOE 与 AD 关系临床研究的原始数据。 这些研究包括 5939 例 AD 病例和 8746 例对照。该提案包括该模型的六种应用和扩展： 1) 研究欧洲血统人群中 APOE 在 AD 中的作用的性别差异。 这将检验关于女性 AD 风险较高的原因以及女性 APOE 基因型导致的 AD 风险差异减小的假设。 2) 使用该模型根据疾病持续时间和症状严重程度预测到 2030 年 AD 病例数。 这将检查以下因素的潜在影响：a) 预计 IHD 死亡率下降；b) 可能减缓 AD 进展的新疗法；以及 c) 可能延迟 AD 发病年龄的新方法。 其中一个重要方面是研究不同假设的影响，即哪些 APOE 基因型将从未来的发展中受益。 3）生成更有效的计算机程序来估计模型的参数。 该模型目前是在电子表格程序中编写的，无法扩展以比较两个以上的人群。 4) 按种族/民族检查 APOE 对 AD 影响的差异。先前的研究表明，APOE 与 AD 白人、非裔美国人、西班牙裔和日本人之间的关系存在很大差异。 这项研究将检验有关 AD 病因学可能差异的假设，这些差异是风险模式差异的基础。 5) 未来几年内，AD 的其他危险因素（尤其是遗传危险因素）很可能会出现重大发现。 这将使跨人群的研究比较和量化个体风险因素的重要性的过程变得复杂。 APOE 和 AD 模型将得到扩展，以包含其他风险因素。