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

项目总结 大约有580万65岁及以上的美国人患有阿尔茨海默氏症，这一数字预计 到2050年增加到1380万。虽然大多数人在65岁或以上出现可诊断的症状(例如 5%-10%的人在或更年轻的时候出现症状，被归类为早发性。早--和晚-- 起病的阿尔茨海默病具有相同的病理基础，但在临床上有重大差异 陈述、生物学表型和对生活的影响。此外，早发性痴呆症比迟发性痴呆更有可能- 由阿尔茨海默氏症以外的其他疾病引起的发作性痴呆，包括血管、路易体和 额颞部退行性变。由于年龄小，症状不典型，早发性患者往往 面临着诊断的重大延误。在如此年轻的年龄起病的痴呆症也不成比例 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和 观察性生物标记物研究和治疗试验。到目前为止，还没有大规模的临床试验专门针对 解决了早发性MCI和痴呆症。阿尔茨海默氏症协会(AA)建议创造和 执行为期两天的会议，每年举行一次，为期三年，题为早发性阿尔茨海默氏症和其他 痴呆症：从自然历史到临床试验。患者、照顾者和家庭成员将参与到 会议的规划、实施和评价部分。美国经济的短期目标 会议的目的是创建一个论坛，讨论研究、试验设计、药物开发和其他问题 在关键利益攸关方之间。长期目标是增加治疗的可能性、质量和以患者为中心 未来针对早发性MCI和痴呆症的临床试验。一个会议工作组，由国际和平与和平组织和 合作者、痴呆症其他主要专家以及早发性MCI或痴呆症和/或 他们的家庭成员将制定、实施和监督所有的会议、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)，并提供说教、小组讨论和基于海报的形式以及面对面 网络机会，预计将有250人参加。关于早期职业生涯的午餐海报会议 调查人员将在会议的两天举行，并将使用多种方法来确保 演讲者和与会者之间的多样性。传播工作将包括网络研讨会、新闻稿、社交 媒体摘要，以及记录会议过程和调查结果的手稿。

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.