NIDUS II: Advanced-Stage Development and Utilization of the NIDUS Research Infrastructure to Advance Interdisciplinary Aging Research in Delirium

精神错乱是一种注意力和认知的急性障碍，是一种常见的、危及生命的和代价高昂的疾病 与阿尔茨海默病和相关痴呆症(ADRD)有密切联系的老年人。2015年，回应 RFA-AG-16-009，我们创建了妄想症调查网络：统一科学家(NIDUS I， R24AG054259)，这是一个由28名调查人员组成的跨学科协作网络，涵盖27个机构， 为&gt；90名学员提供研究资源、会议、试点资助和密集指导，导致&gt；340 第一作者论文和&gt；46作为首席研究员的拨款。尽管取得了这些进展，但仍有一个主要的知识差距 领域仍然是：对精神错乱的安全和有效的治疗。因此，针对PAR-20-071，我们建议 扩大现有的基础设施，如NIDUS II，以促进发展更多所需的基础科学 对精神错乱的有效治疗，并最终改善所有老年人和 和ADRD在一起。我们的具体目标是：(1)协调核心。发展和推广创新测量 与临床研究和临床研究的精神错乱测量、结果和预测因素的协调有关的方法 治疗试验，并改进对ADRD所有阶段患者的胡言乱语诊断和严重程度的措施。 这些方法将使我们能够结合来自多个现有的精神错乱研究的数据；(2)研究 资源核心。开发和扩大NIDUS研究中心，以创建协作基础设施 这将为未来的跨学科研究提供种子，以促进精神错乱的研究(例如，生物标记物研究、干预 发展研究)；(3)试点/探索性研究核心。授予试点和试探性拨款，将 促进跨学科协作研究，旨在利用我们的基础设施和推进研究 需要开发更好的治疗神志不清的方法。为此，我们将组建协作工作组 (工作组)将处理4个科学优先领域：(A)计量：协调和完善计量 精神错乱和相关后果，包括ADRD患者，并确保准确和敏感的措施 用于治疗试验；(B)病理生理学：生物标志物和机制研究，以促进我们的理解和 确定治疗试验的潜在治疗靶点；(C)临床试验：新的干预进展 多组分治疗方法；(D)妄想症和ADRD的相互关系：流行病学、危险因素、 病理生理学、预后，特别是治疗研究；(4)职业发展和外展核心： 对于将利用NIDUS II基础设施并将参与工作组的早期调查人员， 试点研究和培训活动。NIDUS II的每一个方面都被设计为创新的科学发现的种子， 并推动精神错乱的研究朝着一个至关重要的方向发展：开发有效的治疗精神错乱的方法， 包括ADRD的精神错乱。当我们在以前的网络基础上建设时，新的NIDUS II的创新 网络是对基础设施的有目的的应用和扩展，以推进科学探索和 在对老年美国人最有利的特定优先领域产生影响。 。

Delirium, an acute disorder of attention and cognition, is a common, life-threatening, and costly condition for older adults with strong links to Alzheimer’s Disease and Related Dementias (ADRD). In 2015, responding to RFA-AG-16-009, we created the Network for Investigation of Delirium: Unifying Scientists (NIDUS I, R24AG054259), a collaborative interdisciplinary network of 28 investigators spanning 27 institutions which has provided research resources, meetings, pilot grants, and intensive mentorship for >90 trainees, leading to >340 first author papers and >46 grants as principal investigator. Despite this progress, a major knowledge gap in the field remains: safe and effective treatments for delirium. Thus, in response to PAR-20-071, we propose to expand the existing infrastructure as NIDUS II to advance the fundamental science needed to develop more effective treatments for delirium, and ultimately, improve outcomes for delirium in all older adults and in those with ADRD. Our specific aims are: (1) Harmonization Core. To develop and expand innovative measurement methods related to harmonization of delirium measures, outcomes, and predictors for clinical studies and treatment trials, and to refine measures of delirium diagnosis and severity in patients with all stages of ADRD. These approaches will allow us to combine data from multiple existing delirium studies; (2) Research Resources Core. To develop and expand the NIDUS Research Hub to create a collaborative infrastructure that will seed future interdisciplinary studies to advance delirium research (e.g., biomarker studies, intervention development studies); (3) Pilot/Exploratory Studies Core. To award pilot and exploratory grants that will promote collaborative interdisciplinary studies designed to utilize our infrastructure and advance research needed to develop better treatments for delirium. For this aim, we will assemble collaborative working groups (WG) which will address 4 scientific priority areas: (a) Measurement: Harmonize and refine measurement of delirium and related outcomes, including patients with ADRD, and to ensure accurate and sensitive measures for treatment trials; (b) Pathophysiology: Biomarker and mechanistic studies to advance our understanding and identify potential therapeutic targets for treatment trials; (c) Clinical Trials: Intervention development for new multicomponent treatment approaches; (d) Inter-Relationship of Delirium and ADRD: Epidemiologic, risk factor, pathophysiologic, prognostic, and especially treatment studies; (4) Career Development and Outreach Core: for early-stage investigators who will utilize the NIDUS II infrastructure and will be involved in working groups, pilot studies, and training events. Every aspect of NIDUS II is designed to seed innovative scientific discovery, and drive delirium research in a critically important direction: development of effective treatments for delirium, including delirium in ADRD. While we are building on the previous network, the innovation of the new NIDUS II network is the purposeful application and expansion of the infrastructure to advance scientific exploration and impact in specific priority areas of greatest benefit to older Americans. .