A Theoretically Based Memory Training Intervention in Mild Cognitive Impairment

描述（由申请人提供）：阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是认知过程和功能能力逐渐下降。它对患者、护理人员和整个社会都产生了重大影响。患有遗忘性轻度认知障碍（a-MCI）的个体比正常健康的老年人发展为AD的风险更大。鉴于a- mci的认知功能仍然相对完整，它是一个特别有希望的认知训练干预目标，利用保留的认知能力。然而，在MCI方面，很少有控制良好的训练研究。前额叶皮层（PFC）是MCI认知训练的一个有希望和可行的目标。重复滞后训练程序（RLTP）是一种基于理论的、具有临床意义的、创新的递增难度训练程序，旨在训练pfc支持的一般记忆认知过程，并在高功能老年人和轻度认知障碍患者的初步研究中显示出前景。该试点临床试验将在a- mci患者中进行单盲随机对照设计，测试RLTP与理论和经验支持的助记策略使用前训练计划相结合的效果，干预后随访9个月。结果测量经过精心挑选，涵盖了广泛的领域：认知神经心理学、自我报告和日常功能和记忆障碍/元记忆意识的行为测量、生活质量、照顾者负担和神经精神症状。具体目的1是检验a-MCI患者在训练后重复滞后任务的改善假设。具体目标2是验证这一假设，即与未接受干预但与工作人员接触、在实验室工作时间和认知刺激数量相似的a- mci患者（对照组）相比，接受训练干预的a- mci患者（实验组）从基线到训练后，在认知、功能和神经精神测量方面表现出更大的改善。具体目标3是检验在执行功能和元记忆任务上较好的基线表现和较高的教育水平与较高的训练后改善得分相关的假设，以及较高的抑郁症状和年龄与较低的训练后得分相关的假设。具体目标4是测试训练收益在随访中保持的程度。研究结果将提供有关创新训练程序的短期和长期效果的临床相关信息，该程序具有改善日常功能的潜力。他们还将加强对基于pfc的过程在MCI培训干预反应中的可塑性的科学理解，这些过程在个体治疗反应中的作用，以及这种训练减缓AD症状进展的能力。数据还将提供有关不同认知和功能测量的相对敏感性的信息，以及有关具体训练参数、反应预测因素和随访效果的信息，这些信息将用于完善全面临床试验的设计。

DESCRIPTION (provided by applicant): Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is characterized by a gradual decline in cognitive processes and functional abilities. It significantly impacts patients, caregivers, and society as a whole. Individuals with amnestic Mild Cognitive Impairment (a-MCI) are at greater risk for progression to AD than normal healthy older adults. Given that cognitive functioning is still relatively intact in a-MCI, it is a particularly promising target for cognitive training interventions, which capitalize on preserved cognitive abilities. However, there are few well-controlled training studies in MCI. The prefrontal cortex (PFC) is a promising and viable target for cognitive training in MCI. The proposed repetition lag training procedure (RLTP) is a theoretically based, clinically relevant, and innovative incremented difficulty training procedure that is designed to train the PFC-supported general cognitive process of recollection and has shown promise in preliminary studies in high functioning older adults and MCI patients. The proposed pilot clinical trial will test the effects of the RLTP in combination with a theoretically and empirically supported pre-training program in mnemonic strategy use in a single blind randomized controlled design in a-MCI patients, with a 9-month post-intervention follow-up period. Outcome measures were carefully selected to cover a wide range of domains: cognitive neuropsychological, self-report and behavioral measures of everyday functioning and awareness of memory impairment/metamemory, quality of life, caregiver burden, and neuropsychiatric symptoms. Specific Aim 1 is to test the hypothesis that a-MCI patients will improve on the repetition lag task following training. Specific Aim 2 is to test the hypothesis that a-MCI patients who are exposed to the training intervention (experimental group) will show greater improvement in cognitive, functional, and neuropsychiatric measures from baseline to post- training, relative to a-MCI patients who are not exposed to the intervention but who have a similar amount of contact with staff, time in the laboratory, and cognitive stimulation (control group). Specific Aim 3 is to test the hypothesis that better baseline performance on executive function and metamemory tasks and higher education level will be associated with higher post-training improvement scores, and that higher depressive symptoms and age will be associated with lower post-training scores. Specific Aim 4 is to test the degree to which training benefits are maintained at follow-up. Findings will provide clinically relevant information about the short- and long-term effects of an innovative training procedure that has the potential to improve daily functioning. They will also enhance scientific understanding of the malleability of PFC-based processes in response to training interventions in MCI, the role of these processes in individual treatment response, and the ability of such training to slow AD symptom progression. Data will also provide information about the relative sensitivity of different cognitive and functional measures, and about specific training parameters, response predictors and follow-up effects, which will be used to refine the design of a full-scale clinical trial. PUBLIC HEALTH RELEVANCE: Individuals with amnestic Mild Cognitive Impairment (a-MCI) are at greater risk for progression to Alzheimer's Disease (AD) than normal healthy older adults. This pilot clinical trial will test the ability of an innovative and theoretically based memory training intervention to improve cognitive, neuropsychiatric and everyday functioning in a-MCI patients, to maintain that improvement across a 9-month follow-up period, and to slow progression of AD symptoms.