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情况下，神经退行性大脑的变化 疾病(AD)在目前使用传统认知评估检测到症状之前数年发生 范例。这些都不够敏感，无法检测到与 在疾病连续体的早期出现的状态。在这部小说领域，越来越多的人达成共识 认知评估范式是作为更灵敏的临床结果衡量标准的关键。 在MCI-AD临床试验中。及早捕获赤字对于推动该领域向前发展是必要的，因为它正在努力 制定预防战略和新的治疗方法，这可能在以下方面最有效 疾病的最早阶段。除了上述限制外，广泛使用的纸和铅笔测量 被用来检测AD相关的轻度认知障碍(MCI)需要高技能的检查员， 而且是工作人员和时间密集的。现有的计算机化电池在许多方面也有局限性 采用不敏感的衡量模式，而且往往不适用于不同的文化/语言群体。 我们小组在开发“认知压力测试”领域处于领先地位，并证明了 通过引发主动语义干扰(PSI)来强调认知系统，然后测量恢复 PSI代表了一种更敏感的方法来检测临床前阶段的认知功能下降 广告。此外，对PSI的脆弱性和无法从PSI中恢复与大脑高度相关 MRI和AD标志区淀粉样蛋白负荷的变化。这些重要的发现源于 纸笔版本的认知测试通过选择最敏感的来进一步改进 索引和计算机化工具，以减少时间和误差，并增加可获得性和交叉 文化适用性。 我们建议招募250名社区居住的老年人进行纵向检查 三种新的计算机化认知应激测试在检测遗忘型轻度认知障碍中的作用 (MCI)与正常认知。这些新的认知测试，Loewenstein-Acevedo语义量表 干扰-简要计算机化版本(LASSI-BC)，迈阿密前瞻记忆测试-计算机化 版本(MPMT-C)和迈阿密语义干扰和学习测试，扩展版本(Mitsi-le)将 与西班牙裔和西班牙裔美国人中AD临床试验中普遍使用的计算机化认知测量进行比较 非西班牙裔个人。此外，我们将把这些新措施的表现与区域大脑联系起来。 AD标志区MRI改变及ApoE基因分型。我们预测，在患有 健忘型MCI、LASSI-BC、MPMT-C和Mitsi-le的基线和变化分数将表现出更强的 相对于传统的和广泛的，在三年的时间里MRI与脑萎缩加重的相关性 使用了目前可用的计算机化神经心理测量方法。

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.