ACTIVE MIND: An adaptive clinical trial of cognitive training to improve function and delay dementia

项目总结 阿尔茨海默病(ADRD)等痴呆症是美国最昂贵的医疗疾病 影响了500多万美国人21。来自积极研究的分析表明，一种特定的 计算机化认知训练(CTA)在老年人中降低了29%的ADRD风险 十年22岁。[最近的跟踪分析表明，积极的参与者有轻度认知的迹象 将基线的损害(MCI)随机纳入CTA，诊断为ADRD的可能性降低23% 跨度20年23]。虽然这些结果令人鼓舞，但MCI并未得到临床诊断，因此 推荐CT用于ADRD预防的证据尚不确定。多种有效的CT技术 现在存在，但具有明显的认知效果。考虑到认知缺陷在那些患有 轻度认知障碍(MCI)，患有ADRD的风险较高，结合CT技术 可能是最有效的。显著的知识差距仍然是患有以下疾病的人的最佳CT检查(S) MCI尚不清楚。我们获得了临床试验计划拨款，以设计和建立可行性 积极心理试验(AG062368)。我们提出了主动思维的第二阶段，一种自适应的随机- 旨在找出改善MCI患者日常功能的最有效的CT锻炼方法。我们会 进一步量化CT对减少MCI患者ADRD发生率的作用大小。在这个阶段 II试验，我们的主要目标是确定哪种CT臂的功能改善最大- 并且最有可能减少ADRD的发生率。我们的调查人员包括国际 CT、MCI/ADRD、招募和保留、神经心理评估、神经成像、 生物标志物和适应性试验设计。我们的方法是将不同的CT臂与严格的 具有等价参与者期望的主动控制条件。措施将包括创新指数- 日常生活工具活动(IADL)、标准认知评估以及神经功能测试的CES 核磁共振成像和基于血液的新型生物标记物。将对CT的潜在主持人进行评估，以确定 谁受益了。本研究具有创新性，在应用适应性试验方法论方面具有较高的效率 找出减少MCI中ADRD发生率的最有效的CT运动。我们将进一步探索Neu- 核素成像和基于血液的生物标记物作为CT结果的潜在调节因子。我们的前提是 靶向CT可改善日常功能(即IADL)，从而延缓ADRD的发病。我们的 长期目标是改善老年人的功能轨迹，从而遏制ADRD的流行。 这些贡献将是重大的，促进了我们对CT如何成功地实施的理解。 实施了遏制ADRD流行的措施。考虑到推迟干预的重要性是相当大的 阿尔茨海默病发病仅一年将导致该病病例减少920万例 到205024。

PROJECT SUMMARY Dementia such as Alzheimer's disease (ADRD) is the most expensive medical condition20 in the US and affects more than 5 million Americans21. Analyses from the ACTIVE study showed that a specific type of computerized cognitive training (CTa) reduced risk of ADRD among older adults 29% across 10 years22. [Recent follow-up analyses indicate that ACTIVE participants with signs of mild cognitive impairment (MCI) at baseline randomized to CTa were 23% less likely to be diagnosed with ADRD across 20 years23]. While these results are encouraging, MCI was not clinically diagnosed and thus evidence is inconclusive to recommend CT for ADRD prevention. Many efficacious CT techniques now exist but have distinct cognitive effects. Given that cognitive deficits are varied among those with mild cognitive impairment (MCI), who are at higher risk for ADRD, a combination of CT techniques may be most efficacious. Significant knowledge gaps remain as the best CT exercise(s) for those with MCI is unclear. We were awarded a clinical trial planning grant to design and establish the feasibility of the ACTIVE MIND trial (AG062368). We propose phase II of ACTIVE MIND, an adaptive random- ized trial to identify the most efficacious CT exercises to improve everyday function in MCI. We will further quantify the effect size of CT to reduce incident ADRD among persons with MCI. In this phase II trial, our primary objective is to determine which CT arm results in the largest functional improve- ments and has the best probability to reduce ADRD incidence. Our investigators include international experts in CT, MCI/ADRD, recruitment and retention, neuropsychological assessment, neuroimaging, biomarkers, and adaptive trial design. Our approach is to compare different CT arms to a stringent active control condition with equivalent participant expectations. Measures will include innovative indi- ces of instrumental activities of daily living (IADL), standard cognitive assessments, as well as neu- roimaging and novel blood-based biomarkers. Potential moderators of CT will be assessed to identify who benefits. This study is innovative, in the application of adaptive trial methodology to efficiently identify the most efficacious CT exercises to reduce ADRD incidence in MCI. We further explore neu- roimaging and blood-based biomarkers as potential moderators of CT outcomes. Our premise is that targeted CT improves everyday function (i.e., IADL), which subsequently delays ADRD onset. Our long term goal is to improve older adults' functional trajectories and thereby curb ADRD prevalence. The contributions will be significant, advancing our understanding of how CT may be successfully im- plemented to curb ADRD prevalence. Significance is considerable given that an intervention delaying the onset of Alzheimer's disease by only one year will result in 9.2 million fewer cases of the disease by 205024.