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

点击翻译按钮获取中文摘要

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.