Bertens Daniela, Tijms Betty M, Vermunt Lisa, Prins Niels D, Scheltens Philip, Visser Pieter Jelle
Alzheimer Centre, Department of Neurology, VU University Medical Centre, Amsterdam, The Netherlands.
Alzheimer Research Center, Amsterdam The Netherlands.
Alzheimers Dement (N Y). 2017 Sep 21;3(4):513-523. doi: 10.1016/j.trci.2017.08.005. eCollection 2017 Nov.
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.
我们研究了临床前和前驱期阿尔茨海默病（AD）的不同纳入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倡议研究中选取了522名认知正常的受试者和872名轻度认知障碍受试者。比较的纳入标准为：（1）临床前或前驱期AD（淀粉样蛋白标志物异常）；（2）临床前或前驱期AD 1期（淀粉样蛋白标志物异常，损伤标志物正常）；以及（3）临床前或前驱期AD 2期（淀粉样蛋白和损伤标志物异常）。观察指标为淀粉样蛋白、神经元损伤和认知标志物。
在临床前和前驱期AD 2期的受试者中，纳入标准导致磁共振成像上观察到的脑容量测量值和认知标志物下降幅度最大。
纳入标准影响观察到的观察指标恶化率。这对试验设计有影响。
