Dario Bachmann, Maha Wybitul, Andreas Buchmann, Christoph Gericke, Antje Saake, Sandro Studer, Katrin Rauen, Esmeralda Gruber, Kaj Blennow, Henrik Zetterberg, Roger M Nitsch, Christoph Hock, Valerie Treyer, Anton Gietl
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Johnson–Neyman analysis identified the biomarkers, which were used as trial inclusion criteria to estimate sample sizes needed to detect a 30% slowing across cognitive outcomes.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>In the CU, using combined plasma Aβ42/40 and p-tau217 cut-offs for eligibility yielded the lowest sample size estimates for a comprehensive multidomain cognitive composite score, whereas sample sizes were higher for all other inclusion criteria based on single biomarkers. In MCI, estimates were substantially lower and less variable across most inclusion criteria and outcome measures.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>These findings highlight the need for careful consideration of outcome measures, baseline diagnosis, and inclusion criteria, given their substantial effect on sample size estimation in trials.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Aβ SUVR, plasma p-tau217, and the p-tau217/Aβ42 ratio predicted decline across multiple cognitive domains.</li>\n \n <li>Using cohort-specific biomarker cutoffs, sample size estimates were similar for p-tau217 combined with Aβ42/40 or Aβ SUVR.</li>\n \n <li>A multidomain composite best detected AD-related decline.</li>\n \n <li>Outcome measures and eligibility criteria strongly impact sample size estimates, especially in CU.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12538628/pdf/","citationCount":"0","resultStr":"{\"title\":\"Predicting cognitive decline with amyloid-PET, plasma p-tau217, Aβ42/40, and p-tau217/Aβ42 in a community-based cohort – relevance for clinical trial enrollment\",\"authors\":\"Dario Bachmann, Maha Wybitul, Andreas Buchmann, Christoph Gericke, Antje Saake, Sandro Studer, Katrin Rauen, Esmeralda Gruber, Kaj Blennow, Henrik Zetterberg, Roger M Nitsch, Christoph Hock, Valerie Treyer, Anton Gietl\",\"doi\":\"10.1002/alz.70802\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>Identifying at-risk individuals and selecting sensitive cognitive outcome measures are critical for designing efficient clinical trials targeting early Alzheimer's disease (AD) stages.</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>We compared amyloid beta (Aβ)-positron emission tomography (PET), plasma tau phosphorylated at threonine 217 (p-tau217), Aβ42/40, and p-tau217/Aβ42-related decline across neuropsychological and functional measures in 225 individuals (176 cognitively unimpaired (CU), 49 with mild cognitive impairment (MCI). 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引用次数: 0
摘要
识别高危人群和选择敏感的认知结果指标对于设计针对早期阿尔茨海默病（AD）阶段的有效临床试验至关重要。方法：我们比较了淀粉样蛋白β (Aβ)-正电子发射断层扫描（PET），血浆苏氨酸217磷酸化（p-tau217）， a - β42/40和p-tau217/ a - β42在神经心理和功能测量中的相关下降，225例个体（176例认知未受损（CU）， 49例轻度认知障碍（MCI））。Johnson-Neyman分析确定了生物标志物，这些生物标志物被用作试验纳入标准，用于估计检测认知结果减缓30%所需的样本量。结果：在CU中，使用联合血浆a β42/40和p-tau217作为资格截止值，对综合多领域认知综合评分产生了最低的样本量估计，而基于单一生物标志物的所有其他纳入标准的样本量更高。在MCI中，大多数纳入标准和结果测量的估计值明显较低，变化较小。讨论：这些发现强调了仔细考虑结果测量、基线诊断和纳入标准的必要性，因为它们对试验中样本量估计有实质性影响。重点：Aβ SUVR，血浆p-tau217和p-tau217/ a - β42比值预测了多个认知领域的下降。使用群体特异性生物标志物截止值，p-tau217联合Aβ42/40或Aβ SUVR的样本量估计值相似。多域复合最能检测到广告相关的衰退。结果测量和资格标准强烈影响样本量估计，特别是在CU中。
Predicting cognitive decline with amyloid-PET, plasma p-tau217, Aβ42/40, and p-tau217/Aβ42 in a community-based cohort – relevance for clinical trial enrollment
INTRODUCTION
Identifying at-risk individuals and selecting sensitive cognitive outcome measures are critical for designing efficient clinical trials targeting early Alzheimer's disease (AD) stages.
METHODS
We compared amyloid beta (Aβ)-positron emission tomography (PET), plasma tau phosphorylated at threonine 217 (p-tau217), Aβ42/40, and p-tau217/Aβ42-related decline across neuropsychological and functional measures in 225 individuals (176 cognitively unimpaired (CU), 49 with mild cognitive impairment (MCI). Johnson–Neyman analysis identified the biomarkers, which were used as trial inclusion criteria to estimate sample sizes needed to detect a 30% slowing across cognitive outcomes.
RESULTS
In the CU, using combined plasma Aβ42/40 and p-tau217 cut-offs for eligibility yielded the lowest sample size estimates for a comprehensive multidomain cognitive composite score, whereas sample sizes were higher for all other inclusion criteria based on single biomarkers. In MCI, estimates were substantially lower and less variable across most inclusion criteria and outcome measures.
DISCUSSION
These findings highlight the need for careful consideration of outcome measures, baseline diagnosis, and inclusion criteria, given their substantial effect on sample size estimation in trials.
Highlights
Aβ SUVR, plasma p-tau217, and the p-tau217/Aβ42 ratio predicted decline across multiple cognitive domains.
Using cohort-specific biomarker cutoffs, sample size estimates were similar for p-tau217 combined with Aβ42/40 or Aβ SUVR.
A multidomain composite best detected AD-related decline.
Outcome measures and eligibility criteria strongly impact sample size estimates, especially in CU.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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