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

ACTIVE MIND：认知训练的适应性临床试验，可改善功能并延缓痴呆

• 批准号: 10688058
• 负责人: Jennifer Lee O'Brien
• 金额: $ 460.45万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688058
• 关键词: Address; Adoption; Affect; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Amyloid beta-Protein; Attenuated; Award; Behavior; Biological Markers; Blood; Brain; Cerebrum; Clinical Trials; Clinical Trials Design; Cognition; Cognitive; Cognitive deficits; Communities; Data; Dementia; Diagnosis; Disease; Elderly; Exercise; Goals; Grant; Health; Hippocampus; Incidence; Individual; International; Intervention; Investigation; Knowledge; Life; Light; Measures; Medical; Methodology; Mind; Minority Recruitment; Mission; Morbidity - disease rate; Neuropsychology; Outcome; Participant; Performance; Perfusion; Persons; Phase; Play; Prevalence; Prevention; Probability; Protocols documentation; Public Health; Randomized; Recommendation; Research; Research Personnel; Rest; Risk; Role; Structure; Training; Training Technics; United States National Institutes of Health; White Matter Hyperintensity; Work; active control; arm; blood-based biomarker; cerebral microbleeds; clinical diagnosis; clinical practice; cognitive benefits; cognitive testing; cognitive training; computerized; cost; dementia risk; design; disability; executive function; expectation; follow-up; functional gain; functional improvement; high risk; improved; indexing; innovation; instrumental activity of daily living; mild cognitive impairment; neurofilament; neuroimaging; novel; phase II trial; phase III trial; preventive intervention; processing speed; prospective; randomized trial; randomized, clinical trials; recruit; sustained attention; tau-1; trial comparing; trial design; trial planning; white matter

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.

项目摘要 老年痴呆症（如阿尔茨海默氏病（ADRD））是美国最昂贵的医疗条件20 影响了超过500万美国人21。ACTIVE研究的分析表明， 一种类型的计算机认知训练（CTa）降低了老年人ADRD的风险29%， 10年22. [最近的随访分析表明，有轻度认知障碍迹象的ACTIVE参与者， 基线时随机分配至CTa的轻度认知功能障碍（MCI）患者被诊断出患有ADRD的可能性降低23% 20年（23）。虽然这些结果令人鼓舞，但MCI没有临床诊断，因此 目前尚无结论性证据推荐CT用于ADRD预防。许多有效的CT技术 现在已经存在，但有不同的认知效果。考虑到认知缺陷在那些有 轻度认知障碍（MCI），ADRD风险较高，CT技术的组合 可能是最有效的。重大的知识差距仍然是最好的CT练习， MCI不清楚。我们获得了临床试验规划补助金，以设计和建立可行性 ACTIVE MIND试验（AG 062368）。我们提出了第二阶段的积极心态，一个自适应的随机- 一项标准化试验，以确定最有效的CT练习，以改善MCI患者的日常功能。我们将 进一步量化CT减少MCI患者ADRD事件的效应量。在这个阶段 II试验，我们的主要目标是确定哪一个CT组的功能改善最大- 最有可能降低ADRD的发生率。我们的调查人员包括国际 CT、MCI/ADRD、招募和保留、神经心理学评估、神经影像学、 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 主动控制条件下，具有相同的参与者期望。这些措施将包括创新的工业， 工具性日常生活活动（IADL），标准认知评估，以及神经功能缺损， 放射成像和新型血液生物标志物。将对CT的潜在调节者进行评估，以确定 谁受益。本研究具有创新性，在适应性试验方法学的应用上， 确定降低MCI患者ADRD发生率的最有效CT练习。我们进一步探索新- 影像学和基于血液的生物标志物作为CT结果的潜在调节剂。我们的前提是， 靶向CT改善日常功能（即，IADL），其随后延迟ADRD发作。我们 长期目标是改善老年人的功能轨迹，从而遏制ADRD的患病率。 这些贡献将是重大的，推进我们对CT如何成功地应用于临床的理解。 以遏制ADRD的流行。考虑到干预行动拖延时间， 阿尔茨海默氏症发病仅一年将导致920万病例减少 205024