Novel Detection of Early Cognitive and Functional Impairment in the Elderly

 描述（由申请人提供）：越来越多的人认识到，阿尔茨海默病（AD）等疾病在正式诊断前数年就已发生，并且现有的认知和功能评估措施不够敏感，无法检测与该疾病相关的早期变化。这一点至关重要，因为新的治疗方法可能在疾病的最早阶段最有效。此外，FDA指南指出，生物标志物指标的变化不会被视为早期AD新兴疗法临床试验的替代结局，除非它们也显示出具有临床影响。拟议的调查是高度创新的，旨在研究新开发的和新的认知测试的线索回忆和语义干扰（LASSI-L），时间和事件相关的前瞻性记忆（MPMT），和新的基于计算机的功能任务模拟（FTS）在检测微妙的认知和功能障碍，以及这些障碍随着时间的推移的进展的有效性。我们的样本将包括讲西班牙语和英语的老年人诊断与传统的神经心理学措施和临床评估：遗忘型MCI（aMCI），临床前MCI（PreMCI），或认知正常（NC）。在拟议的调查中，我们将进一步建立我们的新的认知和功能措施的可靠性和有效性，以区分诊断组和预测随着时间的推移认知和功能下降的进展。我们还预测，在aMCI和PreMCI受试者中，LASSI-L、MPMT和FTS的基线和变化评分将在至少三年的时间内与传统神经心理学指标相比，与MRI萎缩的增加表现出更强的相关性。该研究的一个令人兴奋的探索性目的将是在PreMCI和aMCI参与者的子样本中探索CSF中淀粉样蛋白、tau和磷酸化tau生物标志物水平与LASSI-L、MPMT和FTS性能之间的关联。

 DESCRIPTION (provided by applicant): There is growing recognition that conditions such as Alzheimer's disease (AD) occur years before a formal diagnosis is rendered and that available cognitive and functional assessment measures are not sufficiently sensitive to detect early changes associated with the condition. This is critical since new treatment approaches are likely to be most effective in the earliest stages of disease. Further, FDA guidelines indicate that changes in biomarker measures will not be considered as surrogate outcomes in clinical trials of emerging therapies for early AD, unless they are also shown to have a clinical impact. The proposed investigation is highly innovative and designed to examine the efficacy of the newly developed and novel cognitive tests of cued recall and semantic interference (LASSI-L), time and event related prospective memory (MPMT), and novel computer-based functional task simulations (FTS) in detecting subtle cognitive and functional impairments, and progression of these impairments over time. Our sample will include Spanish-speaking and English-speaking older adults diagnosed with traditional neuropsychological measures and clinical evaluations as: amnestic MCI (aMCI), pre-clinical MCI (PreMCI), or cognitively normal (NC). In the proposed investigation, we will further establish the reliability and validity of our novel cognitive and functional measures in distinguishing between diagnostic groups and predicting progression of cognitive and functional decline over time. We also predict that among aMCI and PreMCI subjects, baseline and change scores on the LASSI-L, MPMT, and FTS will exhibit stronger associations with increasing MRI atrophy over a minimum three-year period relative to traditional neuropsychological measures. An exciting exploratory aim of the study will be the exploration, among a subsample of PreMCI and aMCI participants, the association between amyloid, tau, and phosphorylated tau biomarker levels in the CSF and performance on the LASSI-L, MPMT and FTS.