Precision-based Assessment for the Detection of Mild Cognitive Impairment in Older Adults

项目摘要 越来越多的人认识到，在阿尔茨海默氏症等疾病中， 在使用传统认知评估检测到症状之前数年， 范例这些都不足以检测到微妙的认知变化相关的 在疾病连续体的早期出现的情况。在小说领域有一个越来越多的共识， 迫切需要认知评估范式作为更敏感的临床结局指标 在MCI-AD临床试验中。及早发现赤字是推动该领域向前发展的必要条件，因为它努力 制定预防策略和新的治疗方法，这可能是最有效的， 疾病的最早阶段。除了上述局限性，广泛使用的纸笔测量 用于检测AD相关的轻度认知障碍（MCI）需要高度熟练的检查者， 并且是人员和时间密集型的。现有的电脑电池也有其局限性，在许多 采用不敏感的测量范式，并且通常不适用于不同的文化/语言群体。 我们的团队是开发“认知压力测试”领域的领导者，并已证明， 通过引发主动语义干扰（PSI）来强调认知系统，然后测量恢复 来自PSI代表了一种更敏感的方法来检测临床前阶段的认知下降， AD.此外，对PSI的脆弱性和无法从PSI中恢复与大脑 MRI上的变化以及AD特征区域中的淀粉样蛋白负荷。这些重要的发现来自于 我们的认知测试的纸笔版本已经通过选择最敏感的 索引和计算机化的文书，以减少时间和错误，并增加可访问性和交叉 文化适用性。 我们建议招募250名居住在社区的老年人， 三种新型计算机化认知应激测试在检测遗忘型轻度认知障碍中的应用 (MCI)与正常认知的对比这些新颖的认知测试，语义的Loewenstein-Acevedo量表 干扰-简明计算机化版本（LASSI-BC），迈阿密前瞻性记忆测试-计算机化 版本（MPMT-C）和语义干扰和学习的迈阿密测试，扩展版本（MITSI-LE）将 将其与西班牙裔和美国人中AD临床试验中普遍使用的计算机化认知测量进行比较， 非西班牙裔人士。此外，我们将把这些新措施的表现与区域大脑 AD特征区域的MRI变化和ApoE基因型。我们预测， 遗忘型MCI、LASSI-BC、MPMT-C和MITSI-LE的基线和变化评分将表现出更强的 与传统和广泛的MRI检查相比， 使用了目前可用的计算机化神经心理学测量方法。

Project Summary There is growing recognition that neurodegenerative brain changes in conditions such as Alzheimer's disease (AD) occur years before symptoms are currently detected using traditional cognitive assessment paradigms. These are not sufficiently sensitive to detect the subtle cognitive changes associated with the condition that occur early in the disease continuum. There is a rising consensus in the field that novel cognitive assessment paradigms are critically needed to serve as more sensitive clinical outcome measures in MCI-AD clinical trials. Capturing deficits early is necessary to move the field forward as it makes efforts to develop both prevention strategies and novel treatment approaches, which are likely to be most effective in the earliest stages of disease. In addition to the above limitations, widely used paper-and-pencil measures employed for the detection of AD-related Mild Cognitive Impairment (MCI) require a highly skilled examiner, and are staff and time intensive. Existing computerized batteries too have their limitations in that many employ insensitive measurement paradigms, and often are unavailable for diverse cultural/language groups. Our group are leaders in the field developing “cognitive stress tests,” and have demonstrated that stressing the cognitive system by eliciting proactive semantic interference (PSI) and then, measuring recovery from PSI represents a more sensitive approach to detecting cognitive decline during the preclinical stages of AD. Moreover, vulnerability to PSI and failure to recover from PSI has been highly associated with brain changes on MRI as well as amyloid load in AD signature regions. These important findings stemming from the paper-and-pencil versions of our cognitive tests have been refined further by selecting the most sensitive indices and computerizing the instruments to reduce time and error, and increase accessibility and cross- cultural applicability. We propose to recruit 250 community-dwelling older adults to conduct a longitudinal examination of the utility of three novel computerized cognitive stress tests to detect amnestic Mild Cognitive Impairment (MCI) versus normal cognition. These novel cognitive tests, the Loewenstein-Acevedo Scales of Semantic Interference- Brief Computerized version (LASSI-BC), Miami Prospective Memory Test- Computerized version (MPMT-C), and Miami Test of Semantic Interference and Learning, Extended version (MITSI-LE) will be compared to ubiquitously used computerized cognitive measures in AD clinical trials among Hispanic and Non-Hispanic individuals. Further, we will relate performance on these novel measures to regional brain changes on MRI in AD signature regions, and ApoE genotype. We predict that among individuals with amnestic MCI, baseline and change scores on the LASSI-BC, MPMT-C, and MITSI-LE will exhibit stronger associations with increasing brain atrophy on MRI over a three-year period relative to traditional and widely used computerized neuropsychological measures that are currently available.