Practice effects of daily functioning across the Alzheimer’s disease spectrum

项目摘要 这一新应用程序的主要目标是展示练习效果较低的个人 在一周内重复测量日常功能，更有可能在认知上取得进展 第二年。该项目还将检查实践是否会对这些基于绩效的 通过比较年龄较大的个体，成年期晚期不同疾病谱的功能分级有所不同 对于患有轻度认知障碍和阿尔茨海默病的人来说，他们的认知是完整的。在一个 探究性目标、各功能量表上的练习效果与不同维度之间的关系 阿尔茨海默病的生物标记物(例如，通过MRI的海马体体积，通过PET的淀粉样沉积， APOE e4)将被研究。这些发现将增加练习效果的支持性证据 正常衰老、轻度认知障碍的诊断、预后和治疗反应的标记物 以及令人发狂的疾病。然而，它将通过关注实践效果来扩展我们之前的工作 功能测量(而我们之前的工作着眼于认知测试的实践影响)。通过意识到 这个务实项目的目标，我们将能够提供更有效的潜力筛选 临床试验的参与者，这将减少参与者的负担和相关的财务成本 这些审判。实践效果也可以用来丰富那些更有可能取得进展和 监测治疗收益作为近期结果的衡量标准。练习的效果也相当可观 对老年认知障碍的诊断和预后的临床益处。这个项目是一致的 以国家老龄问题研究所为使命。 关联性。目前对轻度认知障碍和阿尔茨海默病的临床试验需要 参与者在整个试验中进步/下降，以准确评估实验干预。 尽管现有的生物标记物(例如，tau和淀粉样蛋白成像)被用来识别那些 这些生物标记物可能会取得进展，但它们价格昂贵，具有侵入性。更便宜、侵入性更小、更多 敏感的生物标记物显然是提高这些试验效率所必需的。我们建议采取这种做法 对基于绩效的功能测量的影响可能会填补文献中的这一重要空白。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 功能量表)预测有认知障碍和无认知障碍老年人的认知衰退 减损。我们期望在未来的临床试验中提供支持证据，将实践效果包括在内。 在正常衰老、轻度认知障碍和阿尔茨海默病中。

Project Summary The main objective of this new application is to demonstrate that individuals with low practice effects on measures of daily functioning repeated across one week are more likely to cognitively progress over the following year. This project would also examine if practice effects on these performance-based functional scales 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. In an exploratory aim, the relationship between practice effects on these functional scales and various biomarkers of Alzheimer's disease (e.g., hippocampal volumes via MRI, amyloid deposition via PET, APOE e4) will be studied. 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. However, it will extend our prior work by focusing on practice effects on functional measures (whereas our prior work looked at practice effects on cognitive tests). 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. Current clinical trials in Mild Cognitive Impairment and Alzheimer's disease require participants to progress/decline across the trial to accurately evaluate the experimental intervention. Although existing biomarkers (e.g., tau and amyloid imaging) are being used to identify those most likely to progress, these biomarkers are expensive and invasive. Cheaper, less invasive, and more sensitive biomarkers are clearly needed to make these trials more efficient. We propose that practice effects on performance-based functional measures might fill this important gap in the literature. In the current pragmatic project, we expect to provide clinicians and researchers with a new tool (i.e., practice effects on functional scales) for predicting cognitive decline in seniors with and without cognitive impairments. We expect to provide supporting evidence to include practice effects in future clinical trials in normal aging, Mild Cognitive Impairment, and Alzheimer's disease.