Bertens Daniela, Knol Dirk L, Scheltens Philip, Visser Pieter Jelle
Department of Neurology/Alzheimer Centre, VU Medical Centre, Amsterdam, The Netherlands.
Department of Epidemiology and Biostatistics, VU Medical Centre, Amsterdam, The Netherlands.
Alzheimers Dement. 2015 May;11(5):511-22. doi: 10.1016/j.jalz.2014.05.1754. Epub 2014 Aug 20.
We investigated the pattern of disease progression in the asymptomatic, mild cognitive impairment (MCI), and dementia stage of Alzheimer's disease (AD).
We selected 284 subjects with AD pathology, defined as abnormal levels of amyloid beta 1-42 (Aβ1-42) in cerebrospinal fluid (CSF). Disease outcome measures included six biomarkers and five cognitive markers. We compared differences in baseline measures and decline over 4 years between the AD stages and tested whether these changes differed from subjects, without AD pathology (N = 132).
CSF Aβ1-42 reached the maximum abnormality level in the asymptomatic stage and tau in the MCI stage. The imaging and cognitive markers started to decline in the asymptomatic stage, and decline accelerated with advancing clinical stage.
This study provides further evidence for a temporal evolution of AD biomarkers. Our findings may be helpful to determine stage specific outcome measures for clinical trials.
我们研究了阿尔茨海默病（AD）无症状期、轻度认知障碍（MCI）期和痴呆期的疾病进展模式。
我们选取了284名患有AD病理特征的受试者，其定义为脑脊液（CSF）中β淀粉样蛋白1-42（Aβ1-42）水平异常。疾病结局指标包括六种生物标志物和五种认知标志物。我们比较了AD各阶段之间的基线测量差异以及4年期间的下降情况，并测试了这些变化是否与无AD病理特征的受试者（N = 132）不同。
CSF Aβ1-42在无症状期达到最大异常水平，tau在MCI期达到最大异常水平。影像学和认知标志物在无症状期开始下降，并随着临床阶段的推进而加速下降。
本研究为AD生物标志物的时间演变提供了进一步证据。我们的研究结果可能有助于确定临床试验中特定阶段的结局指标。
