Understanding visual working memory in Alzheimer's disease

描述（由申请人提供）：最近的研究表明，与健康老年人相比，阿尔茨海默病（AD）患者对简单视觉特征具有正常的视觉工作记忆（VWM）能力。相比之下，AD患者对复杂物体的VWM能力降低，这是由于将复杂物体的视觉特征结合在一起的能力受损。理解这种结合障碍背后的认知和神经基础是至关重要的，因为VWM对于基本的视觉任务至关重要，例如导航新环境，注意景观变化，在杂乱的空间中寻找物体以及驾驶。几十年来的研究表明，VWM是一个复杂的过程，可以分为几个处理阶段。这些包括早期的编码阶段，它创建了以前看到的信息的心理表征，以及后期的维护阶段，在不需要外部刺激的情况下存储表征。多个因素介导每个阶段，包括涉及感知，注意力和记忆的因素。重要的是，注意力缺陷突出作为VWM结合障碍的候选来源，因为已知AD患者在某些条件下具有视觉注意力缺陷，并且视觉注意力参与编码和维持阶段。该建议采用行为和脑电图（EEG）方法来确定视觉注意力的变化，而不是感知和记忆，是否是AD患者结合VWM特征的能力减弱的基础。具体目标针对不同的因素，调解VWM阶段的编码和维护。目的1将测试这一假设，即AD相关的VWM结合障碍是由于在将信息编码成VWM的过程中视觉注意力减弱所致。目标1下的一个行为和一个事件相关电位（ERP）实验将使用快速串行视觉呈现（RSVP）任务的变体来确定AD患者的结合错误是否是由导致信息丢失的感知缺陷或导致信息结合不良的注意力缺陷引起的。目的2将测试的假设，AD相关的VWM结合的损害，减少视觉注意力在VWM信息的维护过程中。目标2下的一个ERP实验将使用变化检测任务来确定AD患者对复杂对象的VWM容量降低是否是由于记忆衰退或注意力绑定受损，而一个行为实验将检查基于注意力的排练是否会减少AD患者的VWM绑定错误并导致他们对复杂对象的VWM容量改善。这项研究的结果可能会告知行为应用程序，以适应AD患者的生活环境，根据他们的视觉认知的变化。这些结果也可能为药物管理提供潜在的靶点。这些应用可以通过延长独立生活和改善AD患者的生活质量，帮助减轻家庭和医疗保健系统的经济负担。 公共卫生相关性：阿尔茨海默病患者的视觉工作记忆受损，这是一个对基本视觉能力很重要的过程。这项拟议中的研究将确定这些患者视觉工作记忆缺陷背后的具体机制，针对可能发生缺陷的过程的不同阶段。了解基本视觉处理的这种变化可以用于延长阿尔茨海默病患者的功能能力，可能减轻医疗保健系统的经济负担，并极大地告知阿尔茨海默病患者的护理人员。

DESCRIPTION (provided by applicant): Recent work has shown that patients with Alzheimer's disease (AD) have a normal visual working memory (VWM) capacity for simple visual features when compared to healthy older adults. In contrast, AD patients have reduced VWM capacity for complex objects, resulting from an impaired ability to bind the visual features of complex objects together. Understanding the cognitive and neural basis underlying this binding impairment is critical because VWM is vitally important for basic visual tasks, such as navigating new environments, noting changes in the landscape, finding objects in a cluttered space, and driving. Decades of previous research have indicated that VWM is a complex process that can be divided into several processing stages. These include an early stage of encoding that creates a mental representation of previously viewed information and a later stage of maintenance that stores the representation without requiring external stimulation. Multiple factors mediate each of these stages, including those involving perception, attention, and memory. Importantly, a deficit of attention stands out as a candidate source of VWM binding impairments because AD patients are known to have deficits of visual attention under certain conditions, and visual attention is involved in both encoding and maintenance stages. This proposal employs behavioral and electroencephalogram (EEG) methods to determine whether changes in visual attention, rather than perception and memory, underlie AD patients' diminished ability to bind features in VWM. The specific aims target the different factors that mediate VWM stages of encoding and maintenance. Aim 1 will test the hypothesis that AD-related impairments in VWM binding result from diminished visual attention during the encoding of information into VWM. One behavioral and one event-related potential (ERP) experiment under Aim 1 will use variations of the rapid serial visual presentation (RSVP) task to determine whether AD patients' binding errors result from perceptual deficits that lead to the loss of information or attentional deficits that lead to poor binding of information. Aim 2 will test the hypothesis that AD-related impairments in VWM binding result from diminished visual attention during the maintenance of information in VWM. One ERP experiment under Aim 2 will use a change detection task to determine whether AD patients' reduced VWM capacity for complex objects results from memory decay or impaired attentional binding, while one behavioral experiment will examine whether attention-based rehearsal will reduce VWM binding errors in AD patients and result in their improved VWM capacity for complex objects. The results of this research could potentially inform behavioral applications for accommodating the living environments for AD patients according to changes in their visual cognition. The results could also provide a potential target for pharmacological management. Such applications could help to ameliorate financial burdens on the family and the healthcare system in general by prolonging independent living and improving the quality of life of patients living with AD. PUBLIC HEALTH RELEVANCE: Alzheimer's disease patients suffer from impairments in visual working memory, a process that is important for basic visual abilities. The proposed research will determine the specific mechanism behind these patients' visual working memory deficits, targeting different stages of the process during which the deficit might occur. Understanding such changes to basic visual processing can be applied toward prolonging the functional abilities of those with Alzheimer's disease, potentially relieving a financial burden on the healthcare system and greatly informing caregivers of Alzheimer's disease patients.