The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease: Implications for trial design.
The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease: Implications for trial design.
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DOI：
10.1016/j.trci.2017.08.005
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Visser PJ
中科院分区：
文献类型：
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作者：
Bertens D;Tijms BM;Vermunt L;Prins ND;Scheltens P;Visser PJ
我们研究了临床前和前驱阿尔茨海默病（AD）的不同入选标准对生物标志物和认知标志物变化以及试验样本量估计的影响。我们从阿尔茨海默病神经影像学研究中选择了522名认知正常的受试者和872名轻度认知障碍的受试者。比较的入选标准为（1）临床前或前驱AD（淀粉样蛋白标志物异常）;（2）临床前或前驱AD 1期（淀粉样蛋白标志物异常，损伤标志物正常）;和（3）临床前或前驱AD 2期（淀粉样蛋白和损伤标志物异常）。结果指标为淀粉样蛋白、神经元损伤和认知标志物。在临床前和前驱AD 2期受试者中，入选标准导致磁共振成像和认知标志物的脑体积测量值出现最大降幅。入选标准影响观察到的结局指标恶化率。这对试验设计有影响。
We investigated the influence of different inclusion criteria for preclinical and prodromal Alzheimer's disease (AD) on changes in biomarkers and cognitive markers and on trial sample size estimates. We selected 522 cognitively normal subjects and 872 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study. Compared inclusion criteria were (1) preclinical or prodromal AD (amyloid marker abnormal); (2) preclinical or prodromal AD stage-1 (amyloid marker abnormal, injury marker normal); and (3) preclinical or prodromal AD stage-2 (amyloid and injury markers abnormal). Outcome measures were amyloid, neuronal injury, and cognitive markers. In both subjects with preclinical and prodromal AD stage-2, inclusion criteria resulted in the largest observed decline in brain volumetric measures on magnetic resonance imaging and cognitive markers. Inclusion criteria influence the observed rate of worsening in outcome measures. This has implications for trial design.