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.

该新应用的主要目的是证明 对一周重复认知测​​试的低实践影响可能被确定为 淀粉样蛋白成像和与阿尔茨海默氏病有关的其他生物标志物的“阳性”。这个项目 还将检查短期实践效果和淀粉样蛋白的沉积是否不同 通过将认知完整的老年人与温和的人进行比较，成年后期的频谱 认知障碍和阿尔茨海默氏病。这些发现将增加 练习效应是正常衰老，轻度诊断，预后和治疗反应的标志物 认知障碍和痴呆疾病。通过意识到这个务实项目的目标，我们 将能够为临床试验的潜在参与者提供更有效的筛查，这将 减少与这些试验相关的伯恩的参与和财务成本。练习效果也可能是 用来丰富试验，而这些试验更有可能进步并监测治疗益处作为近端 结果度量。练习效果还具有可用于诊断和预后的临床益处 后期认知障碍。该项目与国家研究所的使命一致 老化。 关联。当前在轻度认知障碍和阿尔茨海默氏病的许多当前临床试验正在使用 生物标志物（例如，淀粉样蛋白成像上的“阳性”，萎缩海马，ApoE E4）作为包含的一部分 标准。同样，生物标志物在诊断阿尔茨海默氏症中变得越来越重要 疾病和其他类型的痴呆症。但是，这些生物标志物中的许多都是昂贵，侵入性的，提供的 很少的临床信息，只能在具有独特资源的网站完成。需要 疾病及其进展的更实际的标记，可用于丰富临床试验。 在一周内对认知测试收集的练习效果可能会填补这一重要空白。在 当前的务实项目，我们希望为临床医生和研究人员提供一种新工具（即实践 效果）预测有或没有认知障碍的老年人中当前的淀粉样蛋白阳性。我们 还将检查短期实践效果与其他相关生物标志物之间的关系 患有阿尔茨海默氏病（例如萎缩性海马，APOE E4，大脑的功能连通性 网络）。我们希望提供支持证据，以将来的临床试验中包括实践效果 正常衰老，轻度认知障碍和阿尔茨海默氏病。