Novel Cognitive Markers of Early Alzheimer's Disease.

项目总结 在识别标志临床前阶段的生物标志物方面已经取得了很大的进展。 阿尔茨海默病(AD)在病理生理过程(如淀粉样蛋白)开始后发生 但在临床症状出现之前。虽然对疾病来说非常有价值 检测发现，生物标志物阳性与临床前AD患者的认知功能水平不相对应， 它也不提供关于未来认知和临床下降的时间表的预后信息。 迫切需要廉价且易于管理的方法来检测和分期AD AS 它的过程从临床前阶段到症状阶段。早期产生的新型神经认知任务 AD病理的行为标记物可以满足这一关键需求。一种认知“压力测试”，可以帮助 作为AD生物标志物阳性个体即将下降的先兆，将是一个重要的 对这一领域的贡献。 拟议的项目将确定两种创新的诊断和预后用途 神经认知任务-视觉感觉绑定(VSB)和视觉短期记忆绑定(VSTMB)- 作为AD病理的新的认知标记物，在疾病的临床前和前驱阶段。 VSB和VSTMB的损害先前已被证明对痴呆症和 由于AD导致的MCI。VSB和VSTMB不受正常衰老、抑郁或非AD痴呆的影响， 因此，这些任务有很大的潜力作为认知标记物来检测和分期早期AD 病理生理学。为了进一步评估这些新任务的临床效用，他们将被应用于 加州大学圣地亚哥分校阿尔茨海默病研究中心(ADRC)的参与者被诊断为 认知正常(CN)或轻度认知障碍(MCI)。来自ADRC临床核心的数据 (临床评分、神经心理测试结果、载脂蛋白E基因分型和脑脊液生物标记物水平) 配合研究的具体任务，以实现目标。 该项目的具体目标是(1)通过以下方式演示VSB和VSTMB的诊断效用 CN生物标志物阳性(CN+)、CN-(CN-)和MCI的性能比较 参与者；(2)通过评估VSB和VSTMB的能力来确定VSB和VSTMB的预后效用 预测认知功能衰退；(2)评估VSB和VSTMB测量纵向变化的能力； (3)探讨VSB和VSTMB与突触功能和脑脊液标志物的相关性。 神经退行性变。 VSB和VSTMB易于管理、价格低廉且无创。他们可以帮助 临床前和先兆AD的检测和分期，并为临床医生和 需要识别早期阿尔茨海默病患者或预测纵向衰退的研究人员。

PROJECT SUMMARY A great deal of progress has been made in identifying biomarkers that signal a preclinical phase of Alzheimer’s disease (AD) that occurs after the onset of pathophysiological processes (e.g., amyloid deposition) but prior to the appearance of clinical symptoms. While extremely valuable for disease detection, biomarker positivity does not correspond to level of cognitive functioning in preclinical AD, nor does it provide prognostic information about the timeline for future cognitive and clinical decline. There is a critical need for inexpensive and easily administered methods of detecting and staging AD as it runs its course from the preclinical to symptomatic stages. Novel neurocognitive tasks that yield early behavioral markers of AD pathology could fill this critical need. A cognitive “stress test” that could serve as a harbinger of impending decline among AD biomarker-positive individuals would be a significant contribution to the field. The proposed project will determine the diagnostic and prognostic utility of two innovative neurocognitive tasks – Visual Sensory Binding (VSB) and Visual Short Term Memory Binding (VSTMB) – as novel cognitive markers of AD pathology during the preclinical and prodromal stages of the disease. Impairment of VSB and VSTMB has previously been shown to be sensitive and specific for dementia and MCI due to AD. VSB and VSTMB are not impacted by normal aging, depression, or non-AD dementias, hence these tasks have great potential as cognitive markers to detect and stage early AD pathophysiology. To further evaluate the clinical utility of these novel tasks, they will be administered to participants from the UC San Diego Alzheimer’s Disease Research Center (ADRC) diagnosed as cognitively normal (CN) or with mild cognitive impairment (MCI). Data from the ADRC Clinical Core (clinical ratings, neuropsychological test results, APOE genotype, and CSF biomarker levels) will be used in tandem with the study-specific tasks to achieve the Aims. Specific aims of the project are (1) To demonstrate the diagnostic utility of VSB and VSTMB by comparing the performance of CN biomarker positive (CN+), CN biomarker negative (CN-) and MCI participants; (2) To determine the prognostic utility of VSB and VSTMB by evaluating their ability to predict cognitive decline; (2a) To evaluate the ability of VSB and VSTMB to measure longitudinal change; and (3) To explore the associations of VSB and VSTMB with CSF markers of synaptic function and neurodegeneration. VSB and VSTMB are easily administered, inexpensive, and noninvasive. They could aid in the detection and staging of preclinical and prodromal AD, and provide a valuable resource to clinicians and researchers who need to identify individuals with early AD or predict longitudinal decline.