INTRODUCTIONAssessing treatments for Alzheimer's disease (AD) relies on reliable tools for measuring AD progression. In this analysis, we evaluate the sensitivity of clinical progression measures in AD within randomized controlled trials (RCTs) with confirmed positive amyloid (Aβ+) status prior to trial enrollment.METHODSExcluding trials targeting non‐cognitive symptoms, we conducted meta‐analyses on progression measures from 25 selected RCTs using R version 4.2.0, along with the metafor and emmeans libraries.RESULTSThe Functional Activities Questionnaire (FAQ) demonstrated the greatest sensitivity over 12 weeks. Other cognitive measures demonstrated lower sensitivity. The integrated Alzheimer's Disease Rating Scale (iADRS) and Clinical Dementia Rating‐Sum of Boxes (CDR‐SB) seemed more effective than their individual cognitive components. Neuropsychiatric measures were the least sensitive in measuring progression.DISCUSSIONFunctional measures generally outperformed other measure categories. Purely cognitive domain‐based measures were suboptimal for tracking early AD progression. Ideally, future measures should incorporate both cognitive and functional components to enhance sensitivity.Highlights Concerns remain regarding the limitations of current outcome measures used in AD clinical trials, particularly their sensitivity in the early and preclinical stages of the disease, which hampers their reliability as indicators of AD progression. The Functional Activities Questionnaire (FAQ) demonstrated the most substantial weighted mean change over 12 weeks, followed by the Mini‐Mental State Examination (MMSE). Functional measures outperformed other measure categories. Composite scores of integrated Alzheimer's Disease Rating Scale and Clinical Dementia Rating‐Sum of Boxes are more sensitive to change than their individual cognitive components, possibly driven by the functional components of the score. Neuropsychiatric measures analyzed in this study appeared to be the least sensitive in measuring progression.

中文翻译：

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评估阿尔茨海默病试验中的临床进展指标：系统评价和荟萃分析


引言阿尔茨海默病 （AD） 的治疗依赖于可靠的工具来测量 AD 进展。在本分析中，我们在随机对照试验 （RCT） 中评估了 AD 临床进展测量的敏感性，这些试验在试验入组前确认了淀粉样蛋白 （Aβ+） 阳性状态。方法包括针对非认知症状的试验，我们使用 R 4.2.0 版以及 metafor 和 emmeans 库对 25 项选定 RCT 的进展测量进行了荟萃分析。结果功能活动问卷 （FAQ） 在 12 周内表现出最高的敏感性。其他认知测量显示敏感性较低。综合阿尔茨海默病评定量表 （iADRS） 和临床痴呆评定量总和 （CDR-SB） 似乎比它们各自的认知成分更有效。神经精神病学测量在测量进展方面最不敏感。讨论功能测量通常优于其他测量类别。纯粹基于认知领域的测量对于跟踪早期 AD 进展是次优的。理想情况下，未来的措施应同时纳入认知和功能成分，以提高敏感性。亮点 对 AD 临床试验中使用的当前结果测量的局限性仍然存在担忧，尤其是它们在疾病早期和临床前阶段的敏感性，这阻碍了它们作为 AD 进展指标的可靠性。功能活动问卷 （FAQ） 显示 12 周内的加权平均变化最大，其次是简易精神状态检查 （MMSE）。功能测量优于其他测量类别。 综合阿尔茨海默病评定量表和临床痴呆评定量-方框总和的综合分数比它们各自的认知成分对变化更敏感，这可能是由分数的功能成分驱动的。本研究中分析的神经精神病学测量似乎在测量进展方面最不敏感。