Risk Evaluation and Education for Alzheimer's Disease

描述(由申请人提供)： 阿尔茨海默病风险评估和教育研究(REVERVE)是一项正在进行的多地点研究项目，旨在通过披露APOE(阿尔茨海默病的一种易感基因)来评估遗传风险评估的心理和行为影响。在这项研究的第一个资助周期，我们开发了一种新的风险评估方法，并进行了一项随机临床试验，其中162名AD患者的一级亲属接受了有或没有APOE披露的遗传风险评估。这项试验的结果表明，通过高度结构化的方案可以安全地披露基因信息。在REVOVE研究的(当前)资金周期中，我们调整了我们的风险曲线，以纳入非裔美国人的数据，我们将297名受试者纳入第二个随机试验，以检验与更传统的遗传咨询方案相比，使用简单、临床上更可行的方案进行遗传风险评估的影响。初步结果表明，简明协议在教育参与者方面与传统协议一样安全有效，因此它将专门用于下一阶段的研究。在下一个研究的资助周期中，我们建议将基因型和表型信息结合起来，创建新的风险估计，纳入轻度认知损害(MCI)的存在或不存在，MCI是一种遗忘性疾病，会增加发展为AD的可能性。由于APOE还会增加心血管疾病的风险，我们还将研究遗传多效性的披露，招募256名受试者，包括60名MCI受试者，参加一项新的随机临床试验，比较提供两种疾病的风险信息和只提供一种疾病的风险信息的影响。我们将在自愿进行遗传风险评估的参与者中增加探索种族和社会认同主题的结果衡量标准。我们还将重新审查前两个资助周期的参与者，以评估遗传风险评估和披露对AD的长期影响，披露后最多10年。这项研究将通过告知政策制定者和临床医生将基因发现整合到医学实践中的安全和有效的方法，对公共健康产生影响。

DESCRIPTION (provided by applicant): The Risk Evaluation and Education for Alzheimer's Disease (REVEAL) Study is an ongoing, multi-site research project that is designed to evaluate the psychological and behavioral impact of genetic risk assessment with disclosure of APOE, a susceptibility polymorphism for Alzheimer's disease. In the first funding cycle of the REVEAL Study, we developed a novel risk assessment methodology and conducted a randomized clinical trial in which 162 first degree relatives of patients with AD received genetic risk assessment with or without APOE disclosure. The results of this trial suggested that genotype information could be disclosed safely with a highly structured protocol. In the (current) funding cycle of the REVEAL Study, we adjusted our risk curves to incorporate data on African Americans, and we have enrolled 297 subjects into a second randomized trial to examine the impact of genetic risk assessment with a brief, more clinically feasible protocol in comparison to a more conventional genetic counseling protocol. Preliminary results suggest that the brief protocol is as safe and effective in educating participants as the conventional protocol, so it will be used exclusively in the next phase of our research. In the next funding cycle of the REVEAL Study we propose to combine genotype and phenotype information, creating new risk estimates that incorporate the presence or absence of mild cognitive impairment (MCI), an amnestic condition which increases the probability of developing AD. Because APOE also increases the risk of cardiovascular disease, we will also study disclosure of genetic pleiotropy by enrolling 256 subjects, including 60 MCI subjects, into a new randomized clinical trial that compares the impact of providing risk information on two diseases to providing risk information on just one. We will add outcome measures that explore themes of race and social identity among participants volunteering for genetic risk assessment. We will also re-examine participants from the first two funding cycles to assess the long-term impact of genetic risk assessment and disclosure for AD up to 10 years following disclosure. This study will have an impact on public health by informing policy makers and clinicians about safe and effective ways to integrate genetic discoveries into the practice of medicine.