Enriching clinical trials requiring amyloid positivity with practice effects

通过实践效果丰富需要淀粉样蛋白阳性的临床试验

• 批准号: 10158384
• 负责人: KEVIN M DUFF
• 金额: $ 72.32万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10158384
• 关键词: Adult; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Amyloid deposition; Atrophic; Biological Markers; Brain; Characteristics; Classification; Clinical; Clinical Trials; Cognition; Cognition Disorders; Cognitive; Data; Dementia; Diagnosis; Disease; Disease Marker; Education; Elderly; Environment; Exposure to; Financial cost; Future; Goals; Hippocampus (Brain); Impaired cognition; Impairment; Individual; Link; Magnetic Resonance Imaging; Materials Testing; Measurement; Memory; Methodology; Mission; Monitor; National Institute on Aging; Odds Ratio; Outcome Measure; Participant; Positron-Emission Tomography; Predictive Value; Prevention trial; Prognosis; Radiation exposure; Relative Risks; Research Personnel; Resources; Sampling; Savings; Scanning; Screening procedure; Senile Plaques; Sensitivity and Specificity; Site; Source; Testing; Therapeutic Clinical Trial; Time; amyloid imaging; apolipoprotein E-4; clinical trial participant; cognitive function; cognitive testing; cost; density; experience; inclusion criteria; male; mild cognitive impairment; normal aging; novel; performance tests; screening; tool; treatment response; trend; β-amyloid burden

The main objective of this new application is to demonstrate that individuals with low practice effects on repeated cognitive testing across one week are likely to be identified as “positive” on amyloid imaging and other biomarkers associated with Alzheimer's disease. This project would also examine if short-term practice effects and amyloid deposition differ across the disease spectrum in late adulthood by comparing older individuals who are cognitively intact to those with Mild Cognitive Impairment and Alzheimer's disease. These findings would add to the supporting evidence of practice effects as a marker of diagnosis, prognosis, and treatment response in normal aging, Mild Cognitive Impairment, and dementing illnesses. By realizing the aims of this pragmatic project, we would be able to offer more efficient screening of potential participants for clinical trials, which would reduce participant burden and financial costs associated with these trials. Practice effects could also be used to enrich trials with those more likely to progress and to monitor treatment benefit as a proximal outcome measure. Practice effects also have considerable clinical benefits for diagnosis and prognosis of cognitive disorders in late life. This project is consistent with the mission of the National Institute on Aging. Relevance. Many current clinical trials in Mild Cognitive Impairment and Alzheimer's disease are using biomarkers (e.g., “positive” on amyloid imaging, atrophic hippocampi, APOE e4) as part of the inclusion criteria. Similarly, biomarkers are becoming increasingly important in the diagnosis of Alzheimer's disease and other types of dementia. However, many of these biomarkers are costly, invasive, provide little clinical information, and may be only completed at sites with unique resources. There is a need for more practical markers of disease and its progression, which could be used to enrich clinical trials. Practice effects, collected on cognitive testing across one week, may fill this important gap. In the current pragmatic project, we expect to provide clinicians and researchers with a new tool (i.e., practice effects) for predicting current amyloid positivity in seniors with and without cognitive impairments. We will also examine the relationship between short-term practice effects and other biomarkers associated with Alzheimer's disease (e.g., atrophic hippocampi, APOE e4, functional connectivity of brain networks). We expect to provide supporting evidence to include practice effects in future clinical trials in normal aging, Mild Cognitive Impairment, and Alzheimer's disease.

这项新申请的主要目的是证明， 一周内重复认知测试的低练习效果可能被确定为 在淀粉样蛋白成像和其他与阿尔茨海默病相关的生物标志物上呈“阳性”。这个项目 还将检查短期练习效果和淀粉样蛋白沉积在疾病中是否存在差异 通过比较认知完整的老年人与轻度认知障碍的老年人， 认知障碍和阿尔茨海默病。这些发现将增加以下方面的支持证据 实践效果作为诊断、预后和治疗反应的标志，在正常衰老、轻度 认知障碍和痴呆症。通过实现这一务实项目的目标，我们 将能够为临床试验提供更有效的潜在参与者筛选， 减少与这些试验相关的参与者负担和财务成本。实践效果也可以是 用于丰富那些更有可能进展的试验，并监测治疗获益， 结果测量。实践效果对诊断和预后也有相当大的临床益处 老年认知障碍该项目符合国家研究所的使命， 衰老 本案无关目前许多轻度认知障碍和阿尔茨海默病的临床试验都使用 生物标记（例如，淀粉样蛋白成像呈“阳性”，萎缩性肌萎缩，APOE e4）作为包涵体的一部分 的搜索.同样，生物标记物在阿尔茨海默氏症的诊断中也变得越来越重要 疾病和其他类型的痴呆症。然而，这些生物标志物中的许多是昂贵的、侵入性的、提供不稳定性的。 临床信息很少，并且可能仅在具有独特资源的研究中心完成。有必要 更实用的疾病及其进展的标志物，可用于丰富临床试验。 通过一周的认知测试收集的练习效果可能会填补这一重要空白。在 当前的实用项目，我们期望为临床医生和研究人员提供一种新的工具（即，实践 用于预测有和没有认知障碍的老年人的当前淀粉样蛋白阳性。我们 还将研究短期实践效果与其他相关生物标志物之间的关系。 患有阿尔茨海默病（例如，萎缩性侧索硬化，载脂蛋白E e4，脑功能连接 网络）。我们希望在未来的临床试验中提供支持性证据，包括实践效果， 正常衰老、轻度认知障碍和阿尔茨海默病。