TY -的T1 -确定临床有意义的临床前阿尔茨海默病摩根富林明下降-神经学乔-神经病学SP - e322 LP - e333做- 10.1212 / WNL。首页0000000000007831六世- 93 - 4盟Philip s . Insel盟-迈克尔·维纳AU - r·斯科特Mackin AU -伊丽莎白Mormino盟日圆应Lim AU - Erik Stomrud AU -塞巴斯蒂安Palmqvist AU -科林·l·大师AU -保罗·t·Maruff AU -奥斯卡·汉森盟Niklas马特Y1 - 2019/07/23 UR - //www.ez-admanager.com/content/93/4/e322.abstract N2 -目标来确定所需的时间为临床前阿尔茨海默病人口下降以一种有意义的方式,使用估计拒绝更首页新之前的临床试验设计的假设,并确定因素修改β-amyloid (Aβ)-相关衰落。方法1120年认知没有个人从3国际军团,我们估计Aβ状态之间的关系和纵向的变化在多个认知域和评估Aβ和基线因素之间的相互作用。权力分析探讨样本大小的函数处理的效果。结果认知没有Aβ+参与者方法轻度认知障碍(MCI)水平的性能基线,6年后平均。实现80%的力量在一个模拟的四年治疗试验中,假设25%的治疗效果,需要2000名参与者/组。多种因素与Aβ预测认知能力下降;然而,这些发现都cohort-specific。尽管整个军团的设计差异,与大样本大小和足够的随访时间,Aβ+组织拒绝始终在认知综合措施。结论临床前广告人口下降早期认知能力的MCI人口6年。这种下降40% - -50%的速度放缓延误临床相关障碍3年可能有意义的治疗效果。然而,假设40% - -50%药物临床前试验设计广告效应凸显了困难的通常认为治疗效果25%结果所需的样本量2000 /组。 Designers of preclinical AD treatment trials need to prepare for larger and longer trials than are currently being considered. Interactions with Aβ status were inconsistent and not readily generalizable.Aβ=β-amyloid; AD=Alzheimer disease; ADNI=Alzheimer's Disease Neuroimaging Initiative; AIBL=Australian Imaging, Biomarkers & Lifestyle; AIC=Akaike information criterion; BioFINDER=Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably; CDR=Clinical Dementia Rating; CDR-SB=CDR sum of boxes; dADASc=Delayed Word Recall from the Alzheimer's Disease Assessment Scale–Cognitive Subscale; dMemory=Logical Memory Delayed Recall; MCI=mild cognitive impairment; MMSE=Mini-Mental State Examination; OR=odds ratio; PACC=Preclinical Alzheimer's Cognitive Composite; PiB=Pittsburgh compound B; SUVR=standardized uptake value ratio; Trails B=Trail-Making Test B ER -