Early-onset Alzheimer’s and other dementia: From natural history to clinical trials

项目摘要 大约有580万65岁及以上的美国人患有阿尔茨海默病，预计这一数字 到2050年增加到1380万。虽然大多数人在65岁或65岁以上出现可诊断的症状（例如， 迟发性），5-10%在64岁或更年轻时出现症状，并被归类为早发性。早-晚- 发病阿尔茨海默病共享相同的病理基础，但在临床上有很大的差异， 介绍，生物表型和生活的影响。此外，早发性痴呆症比晚发性痴呆症更有可能- 由阿尔茨海默病以外的病理引起的发作性痴呆，包括血管性、路易体，以及 额颞叶变性。由于年龄小，症状不典型，早发患者往往 诊断会有很大的延迟。老年痴呆症在如此年轻的时候发病， 对患者、家庭和社会造成毁灭性的经济和情感后果。由于年龄限制或 没有记忆缺陷，早发性患者在正在进行的大规模基因组中代表性不足， 观察性生物标志物研究和治疗试验。到目前为止，还没有大规模的临床试验专门 治疗早发性轻度认知障碍和痴呆阿尔茨海默氏症协会（AA）建议创建和 举办为期两天的会议，每年举行一次，为期三年，题为早发性阿尔茨海默病和其他 痴呆症：从自然史到临床试验患者、护理人员和家庭成员将参与 会议的规划、执行和评价部分。的短期目标 会议的目的是建立一个讨论研究、试验设计、药物开发和其他问题的论坛 关键利益相关者之间。长期目标是增加以患者为中心的 未来的临床试验解决早发性MCI和痴呆症。会议工作组由PI和 合作者，其他痴呆症领域的领先专家，以及早发性MCI或痴呆症患者和/或 他们的家庭成员将制定、实施和监督所有会议、评估和传播 活动这些会议将与一年一度的国际阿尔茨海默氏症协会协调举行 会议（AAIC），并提供教学，小组讨论和海报为基础的格式，以及面对面 网络机会，预计250与会者。午餐海报会议致力于早期的职业生涯 会议的两天都将举行调查，并将采用多种方法来确保 演讲者和与会者的多样性。传播工作将包括网络研讨会、新闻稿、社交媒体、 媒体重点报道以及记录会议记录和调查结果的手稿。

PROJECT SUMMARY Approximately 5.8 million Americans age 65 and older have Alzheimer's disease, and this number is expected to increase to 13.8 million by 2050. While most develop diagnosable symptoms at or over the age of 65 (e.g. late-onset), 5-10% develop symptoms at age 64 or younger and are classified as early-onset. Early- and late- onset Alzheimer's disease share the same pathologic substrate, but there are critical differences in their clinical presentations, biological phenotypes, and life impact. Moreover, early-onset dementia is more likely than late- onset dementia to be caused by pathologies other than Alzheimer's, including vascular, Lewy body, and frontotemporal degeneration. Because of their young age and atypical symptoms, early-onset patients often face a significant delay to diagnosis. Dementia onset at such a young age also has disproportionately devastating financial and emotional consequences for patients, families, and society. Due to age restrictions or absence of memory deficits, early-onset patients are under-represented in ongoing largescale genome and observational biomarker studies and in therapeutic trials. To date, no large-scale clinical trials have specifically addressed early-onset MCI and dementia. The Alzheimer's Association (AA) proposes to create and implement a two-day conference, to be held annually for 3 years, entitled Early-Onset Alzheimer's and Other Dementia: From Natural History to Clinical Trials. Patients, carers, and family members will be involved in the planning, implementation, and evaluation components of the conference. The short-term goal of the conference is to create a forum for discussion of research, trial design, drug development, and other concerns among key stakeholders. The long-term goal is to increase the likelihood, quality and patient-centeredness of future clinical trials addressing early-onset MCI and dementia. A Conference Workgroup made up of the PI and collaborators, additional leading experts in dementia, and individuals with early-onset MCI or dementia and/or their family members will develop, implement, and oversee all conference, evaluation, and dissemination activities. The conferences will be held in coordination with the annual Alzheimer's Association International Conference (AAIC) and offer didactic, panel discussion, and poster based formats, as well as face-to-face networking opportunities, anticipating 250 attendees. Lunch poster sessions dedicated to the early career investigators will be held on both days of the conference, and multiple approaches will be used to ensure diversity amongst speakers and attendees. Dissemination efforts will include webinars, press releases, social media highlights, and manuscripts documenting conference proceedings and findings.