Novel Cognitive Markers of Early Alzheimer's Disease.

项目摘要 在确定标志临床前阶段的生物标志物方面已经取得了很大进展 阿尔茨海默病（AD）的发病后发生的病理生理过程（例如，淀粉样 沉积），但在临床症状出现之前。虽然对疾病非常有价值 检测，生物标志物阳性不对应于临床前AD的认知功能水平， 也不能提供关于未来认知和临床衰退的时间轴的预后信息。 迫切需要廉价且易于管理的检测和分期AD的方法， 它从临床前阶段到症状阶段。新的神经认知任务， AD病理学的行为标志物可以满足这一关键需求。一项认知“压力测试”， 作为AD生物标志物阳性个体即将下降的预兆， 对外地的贡献。 拟议的项目将确定两个创新的诊断和预后效用 神经认知任务-视觉感觉绑定（VSB）和视觉短期记忆绑定（VSTMB）- 作为疾病临床前和前驱期AD病理学的新认知标志物。 VSB和VSTMB的损害先前已被证明对痴呆是敏感和特异的， 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，这些任务作为早期AD检测和分期的认知标记物具有很大的潜力 病理生理学为了进一步评估这些新任务的临床效用，将对这些任务进行管理， 来自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）。数据来自ADRC临床核心 （临床评级、神经心理学测试结果、APOE基因型和CSF生物标志物水平） 与研究特定任务相结合，以实现目标。 该项目的具体目标是：（1）通过以下方式证明VSB和VSTMB的诊断实用性 比较CN生物标志物阳性（CN+）、CN生物标志物阴性（CN-）和MCI的性能 （2）通过评估VSB和VSTMB的能力来确定其预后效用， （2a）评价VSB和VSTMB测量纵向变化的能力; （3）探讨VSB和VSTMB与CSF中突触功能标志物的关系， 神经变性 VSB和VSTMB易于管理，价格低廉，无创。他们可以帮助 临床前和前驱AD的检测和分期，并为临床医生提供有价值的资源， 需要识别早期AD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.