Zammit Andrea R, Capuano Ana W, Barnes Lisa L, Schneider Julie A, Sperling Reisa A, Bennett David A, Grodstein Francine
Rush Alzheimer's Disease Center Rush University Medical Center Chicago Illinois USA.
Department of Psychiatry and Behavioral Sciences Rush University Medical Center Chicago Illinois USA.
Alzheimers Dement (N Y). 2025 Jul 16;11(3):e70137. doi: 10.1002/trc2.70137. eCollection 2025 Jul-Sep.
We evaluated the statistical power for a theoretical randomized trial of anti-amyloid treatment in preclinical Alzheimer's Disease across five cognitive composites in preclinical Alzheimer's Disease across five cognitive composites: Alzheimer's Prevention Initiative Preclinical Composite Cognitive Test (APCC); Preclinical Alzheimer's Composite with Semantic Processing (PACC5); Preclinical Alzheimer's Cognitive Composite (PACC); and global and episodic memory composites.
We utilized annual cognitive assessments from 517 decedents (78.2 ± 4.7years; 72% female) with pathologic Alzheimer's disease (AD) to represent amyloid positivity. We calculated sample sizes to detect 30% reduction in 5-year slopes of cognitive decline for equal size treatment versus placebo groups across composites.
Estimated sample sizes for APCC ( = 1633, 95% confidence interval [CI] 1400-1823), PACC ( = 1822, 95% CI 1612-2122), and episodic memory ( = 3141 95%CI 2563-3732) were larger than for PACC5 ( = 1424, 95% CI 1249-1575). Sample size estimates were similar between PACC5 and the global composite ( = 1267, 95%CI 1336-1407).
Small changes in composites, such as addition of semantic fluency in PACC5, could be considered as part of approaches to improve statistical power.
We evaluated statistical power of a theoretical 5-year randomized trial testing anti-amyloid treatments in early Alzheimer's across five cognitive composite endpoints.We leveraged annual cognitive assessment in Rush Alzheimer's Disease Center cohorts and used pathologic AD to represent amyloid positivity.Preclinical Alzheimer's Composite with Semantic Processing (PACC5) required significantly lower sample size to achieve power for a 30% reduction in cognitive slope than Alzheimer's Disease Cooperative Study-Preclinical Alzheimer's Cognitive Composite (PACC).PACC5 had better statistical power than Alzheimer's Prevention Initiative Preclinical Composite Cognitive Test (APCC) and an episodic memory composite.Small changes in cognitive composites can improve detection of cognitive decline.
我们评估了一项针对临床前阿尔茨海默病抗淀粉样蛋白治疗的理论随机试验在五个认知综合指标上的统计效力，这五个认知综合指标包括：阿尔茨海默病预防计划临床前综合认知测试（APCC）；具有语义处理能力的临床前阿尔茨海默病综合指标（PACC5）；临床前阿尔茨海默病认知综合指标（PACC）；以及整体和情景记忆综合指标。
我们利用了517名患有病理性阿尔茨海默病（AD）的死者（年龄78.2±4.7岁；72%为女性）的年度认知评估结果来代表淀粉样蛋白阳性情况。我们计算了样本量，以检测在各综合指标上，治疗组与安慰剂组规模相等时，5年认知衰退斜率降低30%的情况。
APCC（n = 1633，95%置信区间[CI] 1400 - 1823）、PACC（n = 1822，95% CI 1612 - 2122）和情景记忆（n = 3141，95% CI 2563 - 3732）的估计样本量大于PACC5（n = 1424，95% CI 1249 - 1575）。PACC5与整体综合指标之间的样本量估计相似（n = 1267，95% CI 1336 - 1407）。
综合指标中的微小变化，如在PACC5中增加语义流畅性，可被视为提高统计效力方法的一部分。
我们评估了一项理论上为期5年的随机试验的统计效力，该试验在五个认知综合终点测试早期阿尔茨海默病的抗淀粉样蛋白治疗。我们利用了拉什阿尔茨海默病中心队列中的年度认知评估，并使用病理性AD来代表淀粉样蛋白阳性情况。与阿尔茨海默病合作研究 - 临床前阿尔茨海默病认知综合指标（PACC）相比，具有语义处理能力的临床前阿尔茨海默病综合指标（PACC5）要实现认知斜率降低30%的效力所需的样本量显著更低。PACC5比阿尔茨海默病预防计划临床前综合认知测试（APCC）和一个情景记忆综合指标具有更好的统计效力。认知综合指标中的微小变化可改善对认知衰退的检测。
