Cognitive decline across five cognitive batteries: Sample size implications for clinical trials

IF 4.9 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-07-16 DOI:10.1002/trc2.70137

Andrea R. Zammit, Ana W. Capuano, Lisa L. Barnes, Julie A. Schneider, Reisa A. Sperling, David A. Bennett, Francine Grodstein

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引用次数: 0

Abstract

INTRODUCTION

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.

METHODS

We utilized annual cognitive assessments from 517 decedents (78.2 ± 4.7years; 72% female) with post mortem 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.

RESULTS

Estimated sample sizes for APCC (n = 1633, 95% confidence interval [CI] 1400–1823), PACC (n = 1822, 95% CI 1612–2122), and episodic memory (n = 3141 95%CI 2563–3732) were larger than for PACC5 (n = 1424, 95% CI 1249–1575). Sample size estimates were similar between PACC5 and the global composite (n = 1267, 95%CI 1336–1407).

DISCUSSION

Small changes in composites, such as addition of semantic fluency in PACC5, could be considered as part of approaches to improve statistical power.

HIGHLIGHTS

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 post mortem 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.

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五种认知电池的认知能力下降：临床试验的样本量含义

我们评估了抗淀粉样蛋白治疗临床前阿尔茨海默病的五种认知组合的理论随机试验的统计能力：阿尔茨海默病预防倡议临床前复合认知测试（APCC）；临床前阿尔茨海默病复合语义加工（PACC5）临床前阿尔茨海默氏认知复合症（PACC）；整体记忆和情景记忆的合成。方法：对517例患者(78.2±4.7岁；72%女性)死后病理性阿尔茨海默病（AD）代表淀粉样蛋白阳性。我们计算了样本量，以检测在复合材料中，同等规模治疗组与安慰剂组相比，认知能力下降的5年斜率降低了30%。结果APCC （n = 1633, 95%可信区间[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和全球综合研究的样本量估计值相似（n = 1267, 95%CI 1336-1407）。复合的微小变化，如PACC5中语义流畅性的增加，可以被视为提高统计能力的方法的一部分。我们评估了一项为期5年的理论随机试验的统计能力，该试验测试了抗淀粉样蛋白治疗在早期阿尔茨海默病中的五个认知复合终点。我们利用拉什阿尔茨海默病中心队列的年度认知评估，并使用死后病理性AD来代表淀粉样蛋白阳性。与阿尔茨海默病合作研究-临床前阿尔茨海默病认知复合（PACC）相比，临床前阿尔茨海默病复合与语义处理（PACC5）所需的样本量显着降低了30%的认知斜率。PACC5比阿尔茨海默病预防计划临床前复合认知测试（APCC）和情景记忆复合测试具有更好的统计能力。认知合成的微小变化可以改善对认知衰退的检测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

期刊介绍： Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.