Risk Evaluation and Education for Alzheimer's Disease (REVEAL IV)

描述（由申请人提供）：项目摘要/摘要-阿尔茨海默病风险评估和教育（REVEAL）研究是一项正在进行的多中心随机对照试验系列，提供经验数据，以解决常见疾病遗传易感性测试中的伦理，社会和翻译问题。鉴于确定常见疾病遗传风险因素的全基因组关联研究的扩大以及利用这些标记进行基因检测商业化的相应努力，这项工作变得越来越重要。这些试验的范例是将载脂蛋白E（APOE）基因型作为阿尔茨海默病（AD）风险评估的一部分披露给未受影响的个体。在之前的资助周期中，我们在三个独立的试验中招募了1000名参与者，我们的多学科团队在分析接受遗传风险信息的心理影响和健康行为变化的许多方面方面都非常富有成效。 我们现在提出了第一个翻译遗传学研究，重点放在疾病的轻度早期症状（表型）和已知的遗传标记（基因型）信息可以一起使用，以产生更迫在眉睫的风险预测的情况下。为此，我们将为轻度认知障碍患者绘制基因型特异性风险曲线，轻度认知障碍是一种APOE β 4等位基因与更快进展为AD和对某些药物治疗的差异反应相关的疾病。我们将进行一项新的随机临床试验，以检查“迫在眉睫的风险评估”（即，3年内转化为AD的风险）。 我们还建议开发和验证一种新型工具，我们称之为基因检测能力评估工具，以可靠地评估个人同意基因检测的能力，这对于研究神经精神疾病的临床医生和研究人员来说将很有用。 最后，我们建议系统地研究在REVEAL研究的早期周期中了解其APOE基因型的参与者的长期心理影响和健康行为变化，其中一些人早在2000年就被招募。 这些数据将有助于为关于将遗传风险信息用于常见、复杂疾病的政策和实践提供信息。 公共卫生相关性：REVEAL IV项目叙述：在REVEAL研究的继续中，我们将进行一项新的随机临床试验，以确定与轻度记忆问题患者披露APOE基因型和3年风险估计相关的心理和健康行为变化。我们还将创建一个新的工具，临床医生和研究人员可以使用它来可靠地评估患者同意基因检测的能力，并通过在披露后2-10年跟踪REVEAL研究患者来检查遗传风险评估的长期影响。

DESCRIPTION (provided by applicant): Project Summary/Abstract - The Risk Evaluation and Education for Alzheimer's Disease (REVEAL) Study is an ongoing series of multi-site randomized controlled trials that provide empirical data to address ethical, social and translational issues in genetic susceptibility testing for common diseases. Such work has become increasingly important given the expansion of genome-wide association studies identifying genetic risk factors for common diseases and corresponding efforts to commercialize genetic testing using these markers. Our paradigm for these trials is disclosure of Apolipoprotein E (APOE) genotype as part of risk assessment for Alzheimer's disease (AD) to unaffected individuals. In previous funding cycles we have enrolled 1000 participants in three separate trials, and our multi-disciplinary team has been highly productive in analyzing many aspects of the psychological impact and health behavior changes of receiving genetic risk information. We now propose the first translational genetics study to focus upon the situation where mild early symptoms of a disease (phenotype) and known genetic marker (genotype) information can be used together to produce more imminent risk projections. To do this, we will develop genotype specific risk curves for patients with Mild Cognitive Impairment, a condition where the APOE epsilon 4 allele is associated with more rapid progression to AD and differential response to certain pharmacological treatments. We will carry out a new randomized clinical trial to examine the impact of "imminent risk assessment" (i.e., risk of conversion to AD within 3 years) in these individuals and their care partners. We also propose to develop and validate a novel instrument, which we call the Capacity Assessment Tool for Genetic Testing, to reliably assess an individual's capacity to consent to genetic testing, which will be useful for clinicians and researchers working with neuropsychiatric diseases. Finally, we propose to systematically study the long-term psychological impact and health behavior changes in participants who learned their APOE genotype in earlier cycles of the REVEAL Study, some of whom were enrolled as early as 2000. These data will help inform policy and practice regarding the use of genetic risk information for common, complex diseases. Public Health Relevance: REVEAL IV Project Narrative: In this continuation of the REVEAL Study, we will conduct a new randomized clinical trial to determine the psychological and health behavior changes associated with disclosing APOE genotype and 3-year risk estimates to persons with mild memory problems. We will also create a new instrument that clinicians and researchers can use to reliably evaluate a patient's capacity to consent to genetic testing and examine long-term impact of genetic risk assessment by following REVEAL Study patients 2-10 years following disclosure.