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

项目摘要 这项新应用的主要目的是证明，低练习的个人对 在一周内重复的日常功能测量更有可能在认知上取得进展， 第二年本项目还将研究实践是否对这些基于绩效的 通过比较老年人， 与轻度认知障碍和阿尔茨海默病患者相比，中 探索性目的，这些功能量表的实践效果与各种 阿尔茨海默病的生物标志物（例如，通过MRI测量海马体积，通过PET测量淀粉样蛋白沉积， APOE e4）进行研究。这些发现将增加实践效果的支持证据， 正常衰老、轻度认知障碍、 和令人痴呆的疾病然而，它将通过关注实践效果来扩展我们先前的工作。 功能测量（而我们之前的工作着眼于认知测试的实践效果）。通过实现 这个务实项目的目标，我们将能够提供更有效的筛选潜力， 参与者的临床试验，这将减少参与者的负担和财务费用， 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的试验， 监测治疗获益作为近端结局指标。实践效果也相当可观 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 国家老龄化研究所的使命。 本案无关目前轻度认知障碍和阿尔茨海默病的临床试验需要 参与者在整个试验过程中进步/下降，以准确评估实验干预。 尽管现有的生物标志物（例如，tau蛋白和淀粉样蛋白成像）被用来识别那些最 这些生物标记物价格昂贵且具有侵入性。更便宜，侵入性更小， 显然需要敏感的生物标志物来使这些试验更有效。我们建议， 对基于性能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 对功能量表的影响），用于预测有和无认知功能障碍的老年人的认知功能下降。 损伤我们期望在未来的临床试验中提供包括实践效果的支持证据 在正常衰老、轻度认知障碍和阿尔茨海默病中的作用。

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.