Effects of Cognitive Training on Everyday Cognitive and Brain Function in Parkinson's Disease

路易体痴呆（LBD）包括帕金森病（PD）痴呆和路易体痴呆，在美国有100多万人患有这种疾病。它也是阿尔茨海默病相关痴呆（adrd）之一。目前，药物治疗最多只能为LBD症状提供适度的益处，对于较轻的认知问题也没有有效的治疗方法。认知训练项目在非痴呆PD患者中获得了广泛的普及，在认知领域取得了不同程度的成功。然而，这些好处并没有普遍化，也没有转移到现实生活中。重要的是，这些程序的神经基础在很大程度上是未知的。本研究旨在开发痴呆发病前的早期干预措施，以增加认知储备，帮助患者独立管理日常生活的认知需求。它还解决了NIH-ADRD的规划优先事项，即支持认知障碍患者的直接需求。执行和视觉空间功能障碍是非常常见的，甚至在疾病过程的早期阶段，在LBD影响日常功能。我们之前使用引导图像训练的工作表明，PD患者的运动表现得到改善，特定大脑网络的功能连接增加。在此基础上，我们提出了一项机制随机临床试验，以确定为期6周的心理意象（MI）训练计划在改善日常任务中目标导向的认知技能方面的有效性（目标1），并利用功能磁共振成像（fMRI）和功能连接分析（目标2）在PD患者中研究这种训练的脑机制。可能患有执行功能障碍的轻度至中度疾病的非痴呆性PD患者将被随机分配到实验组（PD- mi）或对照组（PD- con）。PD-MI组将在监督下通过家庭作业练习日常任务的MI，而PD- con组将接受PD的认知功能和大脑健康的心理教育。我们的人工智能培训与现有的认知培训项目有重要的不同之处：它将1)专注于在相关的现实世界任务中提高认知功能，2)促进个性化和实用技能的发展，这些技能可以灵活地应用于现实生活中。目标1的主要认知目标参与结果将是日常生活中自我报告的认知技能测量的改善。Aim 2的主要神经生物学目标参与结果将是在模拟现实世界需求的自然fMRI任务期间协调脑网络相互作用的任务特异性变化。我们还将研究假定的训练后认知功能和功能连接的变化是否会持续12周（目的3）。最后，我们将探讨功能连接变化是否会预测6周和12周时间点的认知结果（探索性目标）。研究结果将为疗效试验提供关键的早期数据，这些试验可能有潜力将心肌梗死发展成一种个性化的神经认知康复计划，涵盖与LBD相关的一系列认知问题。

Lewy body dementia (LBD) encompasses Parkinson’s disease (PD) dementia and dementia with Lewy bodies and afflicts more than one million people in the US. It is also one of the Alzheimer’s disease-related dementias (ADRDs). Currently, pharmacological treatment provides, at most, modest benefit for symptoms of LBD, and there is no effective treatment for milder cognitive problems. Cognitive training programs in nondemented PD patients have gained popularity with varying degrees of success for the cognitive domain that is treated. However, the benefits have not been generalizable and not transferred to real-life tasks. Importantly, the neural basis of these programs is largely unknown. This proposal aims to develop an early intervention before the onset of dementia to increase cognitive reserve and help patients independently manage the cognitive demands of everyday life. It also addresses the NIH-ADRD programmatic priority of supporting the immediate needs of people living with cognitive impairment. Executive and visuospatial dysfunction is very common even in the early stages of the disease process in LBD affecting everyday functioning. Our previous work using guided imagery training showed improved motor performance and increased functional connectivity in specific brain networks in PD patients. Grounded in that work, we now propose a mechanistic randomized clinical trial to determine the effectiveness of a 6-week mental imagery (MI) training program in improving goal-directed cognitive skills during everyday tasks (Aim 1) and to investigate the brain mechanisms of this training using functional magnetic resonance imaging (fMRI) and functional connectivity analyses (Aim 2) in PD patients. Nondemented PD patients with mild-to-moderate disease, who may have executive dysfunction will be randomly assigned in parallel to either the experimental (PD-MI) or control (PD-Con) group. The PD-MI group will practice MI of everyday tasks in a supervised manner and via homework, whereas the PD-Con group will receive psychoeducation on cognitive functioning and brain health in PD. Our MI training differs from existing cognitive training programs in important ways: It will 1) focus on cognitive functional improvement in relevant real-world tasks and 2) foster the development of personalized and practical skills that can be applied flexibly to real-life situations. The primary cognitive target engagement outcome in Aim 1 will be the improvement in self-reported measures of cognitive skills in daily life. The primary neurobiological target engagement outcome in Aim 2 will be the task-specific changes in coordinated brain network interactions during naturalistic fMRI tasks that will mimic real-world demands. We will also examine whether the putative post-training changes in cognitive function and functional connectivity will be sustained over a 12-week period (Aim 3). Finally, we will explore whether the functional connectivity changes will predict the cognitive outcomes at the 6- and 12-week timepoints (Exploratory Aim). Findings will provide critical early data for efficacy trials that may have the potential to develop MI into a personalized neurocognitive rehabilitation program across a spectrum of cognitive issues related to LBD.