Division of Biostatistics, Washington University in St. Louis, St. Louis, Missouri, United States of America.
Comprehensive Center of Aging Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
PLoS One. 2020 Feb 21;15(2):e0228064. doi: 10.1371/journal.pone.0228064. eCollection 2020.
To describe the presence of practice effects in persons with Alzheimer disease (AD) or mild cognitive impairment (MCI) and to evaluate how practice effects affect cognitive progression and the outcome of clinical trials.
Using data from a meta-database consisting of 18 studies including participants from the Alzheimer disease Cooperative Study (ADCS) and the Alzheimer Disease Neuroimaging Initiative (ADNI) with ADAS-Cog11 as the primary outcome, we defined practice effects based on the improvement in the first two ADAS-Cog11 scores and then estimated the presence of practice effects and compared the cognitive progression between participants with and without practice effects. The robustness of practice effects was investigated using CDR SB, an outcome independent the definition itself. Furthermore, we evaluated how practice effects can affect sample size estimation.
The overall percent of practice effects for AD participants was 39.0% and 53.3% for MCI participants. For AD studies, the mean change from baseline to 2 years was 12.8 points for the non-practice effects group vs 7.4 for the practice effects group; whereas for MCI studies, it was 4.1 for non-practice effects group vs 0.2 for the practice effects group. AD participants without practice effects progressed 0.9 points faster than those with practice effects over a period of 2 years in CDR-SB; whereas for MCI participants, the difference is 0.7 points. The sample sizes can be different by over 35% when estimated based on participants with/without practice effects.
Practice effects were prevalent and robust in persons with AD or MCI and affected the cognitive progression and sample size estimation. Planning of future AD or MCI clinical trials should account for practice effects to avoid underpower or considers target trials or stratification analysis based on practice effects.
描述阿尔茨海默病（AD）或轻度认知障碍（MCI）患者中存在的练习效应，并评估练习效应对认知进展和临床试验结果的影响。
利用来自包含 18 项研究的荟萃分析数据库中的数据，这些研究的参与者来自阿尔茨海默病合作研究（ADCS）和阿尔茨海默病神经影像学倡议（ADNI），以 ADAS-Cog11 作为主要结局指标，我们根据 ADAS-Cog11 的前两次评分的改善来定义练习效应，然后估计练习效应的存在，并比较有和无练习效应的参与者之间的认知进展。使用 CDR SB（一种独立于定义本身的结局）来研究练习效应的稳健性。此外，我们还评估了练习效应对样本量估计的影响。
AD 参与者的总体练习效应百分比为 39.0%，MCI 参与者的总体练习效应百分比为 53.3%。对于 AD 研究，无练习效应组从基线到 2 年的平均变化为 12.8 分，而有练习效应组为 7.4 分；而对于 MCI 研究，无练习效应组为 4.1 分，而有练习效应组为 0.2 分。在 CDR-SB 中，无练习效应的 AD 参与者在 2 年内的认知进展比有练习效应的参与者快 0.9 分；而对于 MCI 参与者，差异为 0.7 分。基于有/无练习效应的参与者进行估计时，样本量可能会有超过 35%的差异。
练习效应在 AD 或 MCI 患者中普遍存在且稳健，影响认知进展和样本量估计。未来的 AD 或 MCI 临床试验规划应考虑练习效应，以避免因练习效应导致的研究效力不足，或考虑基于练习效应的目标试验或分层分析。
