Alzheimer's Disease Neuroimaging Initiative (ADNI4)

阿尔茨海默病神经影像倡议 (ADNI4)

基本信息

批准号：
10704643
负责人：
MICHAEL W WEINER
金额：
$ 3288.73万
依托单位：
NORTHERN CALIFORNIA INSTITUTE/RES/EDU
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10704643
关键词：
Acceleration Address Aducanumab Advertising Advisory Committees Algorithms Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease model Amyloid Autopsy Biological Markers Biometry Black race Blood Blood Tests Brain Brain imaging Cerebrovascular Disorders Clinic Clinical Clinical Research Clinical Treatment Clinical Trials Clinical assessments Cognition Cognitive Collection Communities Data Data Collection Dementia Development Diagnosis Diagnostic Diagnostic Procedure Digital biomarker Early Intervention Enrollment Ensure Exclusion Criteria Explosion Face Functional disorder Future Genetic Glial Fibrillary Acidic Protein Goals Harvest Image Impaired cognition Individual Industry Informatics Intervention Knowledge Latinx Leadership Light Location MRI Scans Magnetic Resonance Imaging Marketing Measurement Methods Monitor Multi-Institutional Clinical Trial Natural History Participant Pathology Phase Phenotype Plasma Population Population Heterogeneity Positron-Emission Tomography Prevalence Prevention trial Privacy Publications Relaxation Research Research Personnel Research Support Review Committee Risk Sampling Site Standardization Telephone Tracer Underrepresented Populations Validation Venous blood sampling Work alpha synuclein biobank biomarker validation cohort community engaged research community engagement comorbidity design digital digital assessment digital monitoring digital platform distributed data effective therapy follow-up improved inclusion criteria longitudinal dataset low socioeconomic status method development mild cognitive impairment mixed dementia neurofilament neuroimaging neuropathology novel diagnostics outreach participant enrollment protein TDP-43 public-private partnership recruit repository screening simulation tau Proteins tau-1 treatment trial trial design

项目摘要

Overall: Summary/Abstract The overall goal of ADNI is to validate biomarkers for AD clinical trials. ADNI data is widely used for planning AD trials and use of ADNI data has enabled dramatic changes to trial design, including early intervention strategies. ADNI data was used to design the aducanumab (Aduhlem™) trials leading to FDA approval. We have widely shared clinical/cognitive, imaging, and biomarker data and provided genetic, CSF, and plasma samples to the scientific community leading to over 3600 publications, providing major contributions to the overall knowledge of AD progression and pathophysiology. ADNI4 directly addresses two critical developments in field: incorporation of plasma biomarkers and enhancing recruitment of underrepresented populations (URPs). To address concerns about lack of generalizability, we created the Diversity Task Force which increased enrollment of URPs in ADNI3. This led to the creation of the Engagement Core which will focus on URP recruitment. Our goals are: first, to continue to validate biomarkers for AD clinical trials, and second, to recruit a more diverse participant population to create and share more generalizable data concerning the relationship of biomarkers and pathology to cognitive decline and dementia. This will be accomplished by: 1) Maintaining and widely sharing the digital data, biofluid, genetic and neuropathology repositories; 2) Following ~500 rollover participants from ADNI3, with priority for symptomatic and URP participants; 3) Greatly increasing recruitment of new URPs using a community-engaged approach employing “boots on the ground” recruiters, and navigators to provide digital/telephone support. Additionally, a digital marketing campaign targeted at URPs will screen and longitudinally assess 20,000 participants and identify 4000 (50-60% URPs) for blood collection at Quest Diagnostics phlebotomy centers. Plasma for A 42/40 and phospho-tau, will identify those AD biomarker+ (e.g., amyloid+). We will relax inclusion criteria to allow more comorbidities than in previous ADNI cohorts and thereby increase the prevalence of mixed dementias and cerebrovascular disease. This will facilitate enrollment of ~500 new participants (50-60% URPs, overall 80% amyloid +, 40% cognitively unimpaired, 40% MCI, 20% dementia) into the ADNI in-clinic battery (clinical assessment, MRI, PET, CSF, plasma). Thus, ~1000 participants will be enrolled into the in-clinic portion of ADNI4. The remaining 3500 participants will be followed longitudinally with follow-up blood testing. The MRI Core will add new sequences for cerebrovascular disease and improve harmonization. The PET Core will add new amyloid and tau PET tracers. Project 1 will optimize diagnosis of AD, monitoring change, and compare imaging and plasma biomarkers. In summary, we will recruit a diverse population for multisite clinical trials, demonstrating the feasibility of digital and blood test screening and monitoring participants on treatments. ADNI4 will guide future AD clinical trials and provide longitudinal clinical, biomarker and autopsy data collected since 2004 to investigators worldwide.

总体而言：总结/摘要 ADNI 的总体目标是验证 AD 临床试验的生物标志物，ADNI 数据广泛用于规划 AD。 ADNI 数据的试验和使用使试验设计发生了巨大变化，包括早期干预策略。 ADNI 数据用于设计 aducanumab (Aduhlem™) 试验，并获得 FDA 广泛批准。共享临床/认知、成像和生物标志物数据，并向研究人员提供遗传、脑脊液和血浆样本科学界发表了 3600 多篇出版物，为整体知识做出了重大贡献 AD 进展和病理生理学直接解决了该领域的两个关键发展：合并。血浆生物标志物和加强代表性不足人群（URP）的招募来解决问题。由于缺乏普遍性，我们成立了多元化工作组，增加了 ADNI3 中 URP 的注册人数。这导致了参与核心的创建，该核心将专注于 URP 招聘。我们的目标是：首先，继续验证 AD 临床试验的生物标志物，其次，招募更多样化的参与者群体创建和共享有关生物标志物和病理学与认知的关系的更通用的数据这将通过以下方式实现：1）维护并广泛共享数字数据、生物流体、遗传和神经病理学存储库；2) 关注来自 ADNI3 的约 500 名轮转参与者，优先考虑 3) 通过社区参与大大增加新 URP 的招募；采用“实地启动”招聘人员和导航员提供数字/电话支持的方法。此外，针对 URP 的数字营销活动将筛选和纵向评估 20,000 参与者并确定 4000 个（50-60% URP）用于在 Quest Diagnostics 放血中心采集血液。 A 42/40 和磷酸-tau 的血浆将识别那些 AD 生物标志物+（例如淀粉样蛋白+）。标准允许比以前的 ADNI 队列有更多的合并症，从而增加混合疾病的患病率这将有助于招募约 500 名新参与者（50-60% URP，总体而言，80% 淀粉样蛋白+、40% 认知未受损、40% MCI、20% 痴呆）进入 ADNI 诊所内电池（临床评估、MRI、PET、CSF、血浆）因此，约 1000 名参与者将被纳入临床部分。 ADNI4 的其余 3500 名参与者将接受 MRI 随访。 Core 将添加脑血管疾病的新序列并改善协调性。新的淀粉样蛋白和 tau PET 示踪剂项目 1 将优化 AD 的诊断、监测变化并进行比较。总之，我们将招募不同的人群进行多中心临床试验，展示数字和血液测试筛查和监测参与者 ADNI4 治疗的可行性。将指导未来的 AD 临床试验，并提供自那时以来收集的纵向临床、生物标志物和尸检数据 2004 年致全世界调查人员。

项目成果

期刊论文数量（90）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The effect of subsyndromal symptoms of depression and white matter lesions on disability for individuals with mild cognitive impairment.

DOI：
10.1016/j.jagp.2013.01.021
发表时间：
2013-09
期刊：
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
影响因子：
0
作者：
Mackin RS;Insel P;Tosun D;Mueller SG;Schuff N;Truran-Sacrey D;Raptentsetsang ST;Lee JY;Jack CR Jr;Aisen PS;Petersen RC;Weiner MW;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative

Neurodegenerative disease biomarkers: guideposts for disease prevention through early diagnosis and intervention.

DOI：
10.1016/j.pneurobio.2011.07.004
发表时间：
2011-12
期刊：
PROGRESS IN NEUROBIOLOGY
影响因子：
6.7
作者：
Trojanowski, John Q.;Hampel, Harald
通讯作者：
Hampel, Harald

Is Cerebrospinal Fluid Superoxide Dismutase 1 a Biomarker of Tau But Not Amyloid-Induced Neurodegeneration in Alzheimer's Disease?

DOI：
10.1089/ars.2019.7762
发表时间：
2019-09-10
期刊：
ANTIOXIDANTS & REDOX SIGNALING
影响因子：
6.6
作者：
McLimans, Kelsey E.;Clark, Bridget E.;Willette, Auriel A.
通讯作者：
Willette, Auriel A.

The Brain Health Registry: An internet-based platform for recruitment, assessment, and longitudinal monitoring of participants for neuroscience studies.

脑健康登记处：一个基于互联网的平台，用于神经科学研究参与者的招募、评估和纵向监测。

DOI：
10.1016/j.jalz.2018.02.021
发表时间：
2018-08
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
0
作者：
Weiner MW;Nosheny R;Camacho M;Truran-Sacrey D;Mackin RS;Flenniken D;Ulbricht A;Insel P;Finley S;Fockler J;Veitch D
通讯作者：
Veitch D

Visit-to-Visit Blood Pressure Variability and Longitudinal Tau Accumulation in Older Adults.