A Theoretically Based Memory Training Intervention in Mild Cognitive Impairment

描述(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、照顾者和整个社会都有重大影响。与正常的健康老年人相比，遗忘性轻度认知障碍(a-MCI)患者进展为AD的风险更大。鉴于认知功能在a-MCI中仍然相对完整，它是认知训练干预的一个特别有希望的目标，它利用保留的认知能力。然而，在MCI中，很少有良好控制的培训研究。前额叶皮质(PFC)是MCI认知训练的一个有前景的、可行的靶点。建议的重复滞后训练程序(RLTP)是一种基于理论、临床相关和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，并已在高功能老年人和MCI患者的初步研究中显示出前景。拟议的试点临床试验将测试RLTP结合理论和经验支持的助记策略预培训计划在a-MCI患者中使用的单盲随机对照设计的效果，干预后随访期为9个月。结果指标经过精心选择，涵盖了广泛的领域：日常功能的认知神经心理、自我报告和行为指标，以及对记忆损害/元记忆、生活质量、照顾者负担和神经精神症状的认识。具体目标1是检验a-MCI患者在训练后将改善重复滞后任务的假设。具体目的2是检验这样一种假设，即接受训练干预的a-MCI患者(实验组)在从基线到训练后的认知、功能和神经精神测量方面将比没有接受干预但与工作人员接触、在实验室呆的时间和认知刺激相似的a-MCI患者(控制组)表现出更大的改善。具体目标3是检验这一假设，即在执行功能和元记忆任务上表现更好的基线表现和更高的教育水平将与训练后更高的改善分数相关，更高的抑郁症状和年龄将与训练后更低的分数相关。具体目标4是测试培训效益在后续行动中保持的程度。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，该程序有可能改善日常功能。他们还将加强对基于PFC的过程在应对MCI培训干预时的可塑性、这些过程在个体治疗反应中的作用以及这种培训减缓AD症状进展的能力的科学理解。数据还将提供关于不同认知和功能测量的相对敏感度的信息，以及关于特定训练参数、反应预测器和后续效果的信息，这些信息将用于完善全面临床试验的设计。 公共卫生相关性：与正常的健康老年人相比，遗忘性轻度认知障碍(a-MCI)患者进展为阿尔茨海默病(AD)的风险更大。这项试点临床试验将测试一种创新的、基于理论的记忆训练干预措施的能力，以改善a-MCI患者的认知、神经精神和日常功能，在9个月的随访期内保持这种改善，并减缓AD症状的进展。

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.