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.

路易体痴呆（LBD）包括帕金森病（PD）痴呆和路易体痴呆，在美国困扰着超过一百万人，它也是阿尔茨海默病相关痴呆（ADRD）之一。最多只能对 LBD 症状产生一定程度的益处，而且对于较轻微的认知问题，目前还没有有效的治疗方法。针对非痴呆 PD 患者的认知训练计划已获得普及，并在所治疗的认知领域取得了不同程度的成功。然而，这些好处尚未得到推广，也没有转移到现实生活中的任务中。重要的是，这些项目的神经基础在很大程度上尚不清楚。该提案旨在在痴呆症发作前开发早期干预措施，以增加认知储备并独立帮助患者。它还解决了 NIH-ADRD 计划的优先事项，即支持认知障碍患者的直接需求，即使在影响日常功能的 LBD 疾病过程的早期阶段，执行和视觉空间功能障碍也很常见。 .我们之前的工作使用引导图像训练显示 PD 患者特定大脑网络的运动表现得到改善，功能连接也得到增强。基于这项工作，我们现在提出一项机械随机临床试验，以确定为期 6 周的心理意象 (MI) 训练计划在改善目标方面的有效性。日常任务中的定向认知技能（目标 1），并使用功能磁共振成像（fMRI）和功能连接分析（目标 2）对患有轻度至中度疾病的帕金森病患者研究这种训练的大脑机制，谁可能拥有执行权功能障碍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 组则将被随机分配到实验组 (PD-MI) 或对照组 (PD-Con)。将接受有关 PD 认知功能和大脑健康的教育。我们的 MI 培训在重要方面不同于现有的认知培训计划：它将 1) 侧重于相关现实世界任务中的认知功能改善，2) 促进个性化和实用性的发展。可以灵活运用到现实生活中的技能目标 1 中的主要认知目标参与结果将是日常生活中认知技能的自我报告测量的改善，目标 2 中的主要神经生物学目标参与结果将是自然主义期间协调的大脑网络交互的特定于任务的变化。模拟现实世界需求的功能磁共振成像任务。我们还将检查认知功能和功能连接的假定训练后变化是否会持续 12 周（目标 3）。变化将预测6 周和 12 周时间点的认知结果（探索性目标）将为功效试验提供关键的早期数据，这些试验可能有可能将 MI 发展为针对与 LBD 相关的一系列认知问题的个性化神经认知康复计划。