Enriching clinical trials requiring amyloid positivity with practice effects

这一新应用程序的主要目标是展示具有 在一周的重复认知测试中，练习效果低很可能被确定为 淀粉样蛋白成像和其他与阿尔茨海默病相关的生物标记物呈“阳性”。这个项目 还将检查短期练习效果和淀粉样蛋白沉积是否因疾病而异 通过比较认知能力完好的老年人和轻度认知障碍的老年人来研究成年后期的光谱 认知障碍和阿尔茨海默病。这些发现将增加支持证据 作为正常衰老、轻度衰老患者诊断、预后和治疗反应的指标 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，这将 减少与这些试验相关的参与者负担和财务成本。练习的效果也可能是 用来丰富那些更有可能取得进展的试验，并作为近端监测治疗益处 结果衡量标准。练习效果对诊断和预后也有相当大的临床益处。 晚年的认知障碍。该项目与国家研究院的使命是一致的 衰老。 关联性。目前许多针对轻度认知障碍和阿尔茨海默病的临床试验都在使用 作为包涵体的一部分的生物标记物(例如，淀粉样蛋白成像上的“阳性”、萎缩的海马区、载脂蛋白e4) 标准。同样，生物标志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，这些生物标记物中的许多都是昂贵的、侵入性的、提供了 临床信息很少，可能只在拥有独特资源的网站上完成。有必要 更实用的疾病及其进展标志物，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 目前的务实项目，我们希望为临床医生和研究人员提供一个新的工具(即实践 用于预测有和没有认知障碍的老年人目前的淀粉样蛋白阳性。我们 还将研究短期练习效果与其他相关生物标志物之间的关系 阿尔茨海默病(例如，海马体萎缩、载脂蛋白E e4、脑功能连接 网络)。我们希望提供支持证据，以包括在未来的临床试验中的实践效果 正常衰老、轻度认知障碍和阿尔茨海默病。

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.