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

认知训练对帕金森病患者日常认知和脑功能的影响

• 批准号: 10855696
• 负责人: Sule Tinaz
• 金额: $ 41.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-10 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10855696
• 关键词: Admission activity; Affect; Aging; Awareness; Brain; Brain imaging; Clinical; Clip; Cognition; Cognitive; Cognitive deficits; Communities; Control Groups; Data; Deterioration; Development; Disease; Elderly; Event; Executive Dysfunction; Fostering; Functional Magnetic Resonance Imaging; Goals; Hospitals; Image; Image Analysis; Imagery; Individual; Informal Social Control; Kinesthesis; Life; Life Expectancy; Link; Measures; Methodology; Modeling; Motivation; Motor; Neurobiology; Neurocognitive; Nursing Homes; Outcome; Parkinson Disease; Parkinson' s Dementia; Patient Self-Report; Patients; Performance; Pharmacological Treatment; Phase; Process; Protocols documentation; Psyche structure; Qualifying; Randomized; Recreation; Rehabilitation therapy; Self Efficacy; Symptoms; Testing; Training; Training Programs; Work; active control group; brain health; cognitive disability; cognitive function; cognitive impairment in Parkinson' s; cognitive load; cognitive skill; cognitive testing; cognitive training; design; effective therapy; effectiveness evaluation; efficacy trial; executive function; experience; experimental group; falls; flexibility; functional MRI scan; functional improvement; improved; instrumental activity of daily living; mental imagery; nervous system disorder; neurocognitive test; neuroimaging; non-demented; novel; prevent; programs; psychoeducation; psychoeducational; randomized, clinical trials; skills; success; treatment strategy; visual imagery; visual motor

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.

Lewy身体痴呆症（LBD）涵盖了帕金森氏病（PD）痴呆和痴呆症，其中有Lewy的身体和折磨超过100万人。它也是阿尔茨海默氏病与疾病相关的痴呆症（ADRDS）之一。目前，药物治疗最多可为LBD症状提供适度的益处，并且对于米勒认知问题没有有效的治疗方法。在非专长的PD患者中的认知培训计划在经过治疗的认知领域的成功程度不同。但是，这些好处并不是可以推广的，也没有转移到现实生活中。重要的是，这些程序的中性基础在很大程度上是未知的。该建议旨在在痴呆症发作之前进行早期干预，以增加认知储备，并帮助患者独立管理日常生活的认知需求。它还解决了支持认知障碍者的直接需求的NIH-ADRD计划优先级。即使在LBD疾病过程的早期阶段，执行和视觉功能障碍也很常见，从而影响每天的运作。我们先前使用带导图像的训练的工作表明，PD患者的特定脑网络中运动性能的提高和功能连通性提高。基于这项工作，我们现在提出了一项机械随机临床试验，以确定6周心理成像（MI）培训计划在每天任务中提高目标指导的认知能力（AIM 1）的有效性（AIM 1），并使用功能磁共振成像（fMRI）（fMRI）（fMRI）和功能连接性分析（AIM 2）（AIM 2）中的训练的大脑机制（AIM 2）。可能患有执行功能障碍的轻度至中度疾病患者的非核心PD患者将与实验（PD-MI）或对照组（PD-CON）组并行分配。 PD-MI组将以监督的方式练习每天的任务MI，并通过家庭作业，而PD-CON组将在PD中接受有关认知功能和大脑健康的心理教育。我们的MI培训与现有的认知培训计划不同：1）关注相关现实世界任务的认知功能改进，以及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。 AIM 1中的主要认知目标参与结果将是改善日常生活中认知技能的衡量标准。 AIM 2中的主要神经生物学目标参与结果将是在自然主义的FMRI任务中，在模仿现实世界中需求的自然fMRI任务期间，任务特定的大脑网络相互作用的变化。我们还将检查假定的认知功能训练后变化和功能连通性是否会在12周的时间内维持（AIM 3）。最后，我们将探讨功能连接性变化是否会预测6周和12周时间点的认知结果（探索目的）。调查结果将为效率试验提供关键的早期数据，这些数据可能有可能在与LBD相关的认知问题范围内开发MI成一个个性化的神经认知康复计划。