Planning an Adaptive Clinical Trial of Cognitive Training to Improve Function and Delay Dementia

规划认知训练的适应性临床试验以改善功能并延缓痴呆

• 批准号: 9791317
• 负责人: Jerri Edwards
• 金额: $ 97.9万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9791317
• 关键词: Alzheimer' s Disease; Applications Grants; Attention; Attenuated; Biological Markers; Blood; Blood Vessels; Brain; Characteristics; Clinical Research; Clinical Trials; Clinical trial protocol document; Cognition; Cognitive; Cognitive deficits; Data; Dementia; Development; Diagnosis; Education; Elderly; Enrollment; Ethnic Origin; Exercise; Goals; Grant; Health; Hippocampus (Brain); Incidence; Individual; International; Intervention; Investigation; Life; Living Standards; Manuals; Measures; Medical; Methodology; Minority Recruitment; Mission; Morbidity - disease rate; Neuropsychology; Outcome; Outcome Measure; Participant; Perfusion; Persons; Phase; Population; Prevalence; Prevention; Preventive; Probability; Procedures; Protocols documentation; Public Health; Race; Randomized; Randomized Clinical Trials; Recommendation; Research; Research Training; Rest; Risk; Sample Size; Sampling; Structure; Testing; Time; Training; Training Technics; United States National Institutes of Health; White Matter Hyperintensity; Work; active control; arm; blood-based biomarker; cerebral microbleeds; clinical Diagnosis; cognitive testing; cognitive training; community planning; cost; dementia risk; design; disability; expectation; functional decline; high risk; improved; improved functioning; indexing; innovation; instrumental activity of daily living; mild cognitive impairment; neuroimaging; neuroimaging marker; neurotropic; novel; pilot trial; processing speed; recruit; sex; simulation; social; success; sustained attention; white matter

PROJECT SUMMARY Our analyses from the ACTIVE study showed that one type of targeted cognitive training (CT) reduced risk of dementia by up to 48% across 10 years. While these results are encouraging, evidence is inconclusive to rec- ommend CT for dementia prevention. Many efficacious CT techniques now exist, but have distinct cognitive effects. Given that cognitive deficits are varied among those at risk for dementia, a combination of CT tech- niques may be most efficacious. Emerging evidence indicates that combining CT techniques can either en- hance or attenuate cognitive gains. However, no studies have been designed to determine the most efficacious CT combinations. Furthermore, no studies have been designed to examine the longitudinal effects of CT on dementia diagnoses. We will engage international experts in CT, mild cognitive impairment (MCI)/dementia, recruitment and retention, neuropsychological assessment, neuroimaging, biomarkers, and adaptive trial de- sign to plan and pilot test an adaptive randomized clinical trial (RCT). The RCT will determine the most effica- cious combinations of CT exercises to attenuate functional decline and delay dementia among older adults at risk due to MCI. We will first develop an effective recruitment plan of community engagement to include those often under-represented in clinical research and enroll a sample representative of the US older adult popula- tion with regard to sex, ethnicity, race, and education. In phase I a pilot trial will be conducted to refine the re- cruitment and retention plan, establish feasibility and finalize procedures, and examine the potential efficacy of 4 CT arms relative to an active control. We will apply improved methodology by comparing the CT arms to a stringent active control condition of cognitive stimulation with equivalent participant expectations and social in- teraction. Measures will include innovative indices of instrumental activities of daily living (IADL), standard cog- nitive assessments, as well as neuroimaging and blood-based biomarkers. Potential moderators of CT will also be assessed. The phase I pilot data will inform statistical simulations to design a seamless phase II/III adaptive RCT. We will simulate participant accrual and several treatment scenarios. For each scenario, we will deter- mine statistical power and sample size required for trial success. The results of these statistical simulations will be applied to optimize design and power for the phase II/III adaptive RCT. The resulting RCT will be innova- tive, in our opinion, in the application of adaptive trial methodology to efficiently identify the most efficacious combinations of CT exercises to delay dementia onset. We will plan the first trial to compare combinations of CT exercises on conversion to dementia among persons with MCI. We will document CT-related changes in the brain with neuroimaging and explore blood-based biomarkers as potential intermediary outcomes of CT. The long term goal is to apply the best CT techniques to delay dementia onset, thereby promoting public health. The contributions will be significant, advancing our understanding of how CT may be implemented to curb dementia prevalence.

项目概要 我们对 ACTIVE 研究的分析表明，一种有针对性的认知训练 (CT) 可以降低以下风险： 10 年内痴呆症发病率高达 48%。虽然这些结果令人鼓舞，但没有确凿的证据表明 建议CT预防痴呆。现在存在许多有效的 CT 技术，但具有不同的认知能力 影响。鉴于痴呆症风险人群的认知缺陷各不相同，CT 技术的结合 尼克斯可能是最有效的。新出现的证据表明，结合 CT 技术可以实现 增加或减弱认知收益。然而，尚无研究旨在确定最有效的 CT 组合。此外，尚无研究旨在检验 CT 对患者的纵向影响。 痴呆症诊断。我们将聘请 CT、轻度认知障碍 (MCI)/痴呆症、 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 签署计划并试点测试适应性随机临床试验 (RCT)。 RCT 将确定最有效的 CT 练习的巧妙组合可减轻老年人的功能衰退并延缓痴呆 MCI 带来的风险。我们将首先制定一个有效的社区参与招聘计划，其中包括那些 在临床研究中代表性不足，并招募代表美国老年人群的样本 性别、民族、种族和教育方面的差异。在第一阶段，将进行试点试验以完善重新设计 招聘和保留计划，建立可行性并最终确定程序，并检查潜在的功效 相对于主动控制的 4 个 CT 臂。我们将通过将 CT 臂与 具有同等参与者期望和社会影响的认知刺激的严格主动控制条件 互动。措施将包括工具性日常生活活动创新指数（IADL）、标准认知 原始评估，以及神经影像学和血液生物标志物。 CT 的潜在主持人也将 进行评估。第一阶段试点数据将为统计模拟提供信息，以设计无缝的第二/第三阶段自适应系统 随机对照试验。我们将模拟参与者的累积和几种治疗场景。对于每种情况，我们都会阻止- 挖掘试验成功所需的统计功效和样本量。这些统计模拟的结果将 用于优化 II/III 期自适应 RCT 的设计和功率。由此产生的随机对照试验将是创新的 我们认为，应用适应性试验方法来有效地识别最有效的方法 CT 练习组合可延缓痴呆症的发作。我们将计划第一次试验来比较以下组合 关于 MCI 患者转变为痴呆的 CT 练习。我们将记录与 CT 相关的变更 通过神经影像学研究大脑，并探索基于血液的生物标志物作为 CT 的潜在中间结果。 长期目标是应用最好的CT技术来延缓痴呆症的发病，从而促进公众 健康。这些贡献将是巨大的，将增进我们对如何实施 CT 的理解 遏制痴呆症患病率。