Prospective memory impairment in Parkinson disease-related cognitive decline: Intervention and mechanisms

艾琳·R·福斯特 R01 AG065214-01A1 帕金森病相关认知功能减退患者的前瞻性记忆障碍：干预及机制 项目摘要/摘要 帕金森病痴呆症(PDD)是阿尔茨海默病相关痴呆症(ADRD)之一，与帕金森病患者的残疾、死亡率和医疗费用增加有关。这项研究的长期目标是通过使PDD高危人群能够应对认知衰退以维持日常功能来减少残疾和延缓ADRD PDD的发病。现有的治疗帕金森病的药物(如手术、药物)并不能预防或治疗认知功能障碍，因此，减轻其负面功能后果并可能延缓或延缓PDD的行为干预是研究的重中之重。不幸的是，广泛使用的认知干预(旨在挑战和改善特定认知功能的任务的重复练习)的过程训练方法在改善这一人群的日常功能和生活质量方面并不成功。为了克服这一限制，研究人员采取了策略培训的方法，教授人们可以在日常生活中使用的有针对性的策略，以绕过认知缺陷，完成日常任务。策略训练是脑损伤和卒中认知康复的实践标准，但它在PDD中的应用是新的。此外，为本研究开发的策略训练干预明确地侧重于将训练推广到日常功能，这是许多典型的策略训练方法和迄今为止与PD相关的认知干预研究严重缺乏的一个方面。这个项目致力于前瞻记忆，即记住在未来适当的时候执行延迟意图的能力。良好的前瞻性记忆力对于独立生活(如支付账单、关掉炉子)、就业、社会关系以及遵守重要的健康行为(如服药)至关重要。有PDD风险的人有前瞻性记忆缺陷，这与较差的日常功能和生活质量有关。因此，在这一人群中，前瞻记忆障碍是一个需要解决的相关认知问题。本项目的主要目标是确定机械定向策略训练对PDD高危人群(PD相关轻度认知障碍者；PD-MCI)前瞻记忆的有效性。这是一项单盲随机对照试验，比较了策略训练和传统过程训练方法对客观实验室前瞻记忆成绩(目标1)和已报道的日常前瞻记忆功能(目标2)的影响。其他目标是研究PD-MCI的前瞻记忆损害的神经机制(Aim 3)和前瞻记忆训练反应的神经和行为预测因子(Aim 4)。该项目利用来自PD、PD-MCI、PDD和对照参与者的现有纵向队列的参与者、数据和基础设施来评估短期和长期培训效果、神经生物学机制和治疗反应的预测因素。这项工作将满足对有效的认知干预的迫切需求，以延缓与ADRD PDD相关的功能损害，并将对这一人群的功能和生活质量产生积极影响。

Erin R. Foster R01 AG065214-01A1 Prospective memory impairment in Parkinson disease-related cognitive decline: Intervention and mechanisms PROJECT SUMMARY/ABSTRACT Parkinson disease dementia (PDD) – one of the Alzheimer’s Disease Related Dementias (ADRD) – is associated with increased disability, mortality and healthcare costs among people with PD. The long term goal of this research is to reduce disability and delay the onset of the ADRD PDD by enabling people at risk for PDD to cope with cognitive decline to maintain daily function. Existing medical (e.g. surgical, pharmacological) treatments for PD do not prevent or treat cognitive impairment, so behavioral interventions that mitigate its negative functional consequences and potentially delay or slow PDD are a top research priority. Unfortunately, the widely-used process training approach to cognitive intervention (repetitive practice of tasks designed to challenge and improve particular cognitive functions) has been unsuccessful in improving daily function and quality of life in this population. To overcome this limitation, the investigators take a strategy training approach, teaching targeted strategies that people can use in their everyday lives to circumvent cognitive deficits and accomplish daily tasks. Strategy training is a practice standard for cognitive rehabilitation in brain injury and stroke, but its application to PDD is novel. Moreover, the strategy training intervention developed for this study explicitly focuses on generalization of training to daily function, an aspect that is critically lacking from many typical strategy training approaches and from PD-related cognitive intervention research to date. This project addresses prospective memory, or the ability to remember to execute delayed intentions at the appropriate moment in the future. Good prospective memory is essential for independent living (e.g. paying bills, turning the stove off), employment, social relationships, and compliance with important health behaviors (e.g. taking medications). People at risk for PDD have prospective memory deficits that relate to worse daily function and quality of life. Therefore, prospective memory impairment is a relevant cognitive problem to address in this population. The primary objective of the current project is to determine the efficacy of mechanistically-targeted strategy training on prospective memory among people at risk for PDD (those with PD-related mild cognitive impairment; PD-MCI). It is a single-blind randomized controlled trial comparing the effects of strategy training to the traditional process training approach on objective laboratory prospective memory performance (Aim 1) and reported everyday prospective memory function (Aim 2). Additional objectives are to investigate neural mechanisms of prospective memory impairment in PD-MCI (Aim 3) and neural and behavioral predictors of prospective memory training response (Aim 4). This project leverages participants, data and infrastructure from an existing longitudinal cohort of PD, PD-MCI, PDD and control participants to evaluate short-term and long-term training effects, neurobiological mechanisms, and predictors of treatment response. This work will meet the pressing need for effective cognitive interventions that delay functional impairment associated with the ADRD PDD and will positively impact function and quality of life in this population.