ADNI遗忘型轻度认知障碍中的生物学异质性。
Biological heterogeneity in ADNI amnestic mild cognitive impairment.
作者信息
Nettiksimmons Jasmine, DeCarli Charles, Landau Susan, Beckett Laurel
机构信息
Department of Psychiatry, University of California-San Francisco, San Francisco, CA, USA.
Department of Neurology and Center for Neuroscience, University of California-Davis, Sacramento, CA, USA.
出版信息
Alzheimers Dement. 2014 Sep;10(5):511-521.e1. doi: 10.1016/j.jalz.2013.09.003. Epub 2014 Jan 10.
BACKGROUND
Previous work examining normal controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) identified substantial biological heterogeneity. We hypothesized that ADNI mild cognitive impairment (MCI) subjects would also exhibit heterogeneity with possible clinical implications.
METHODS
ADNI subjects diagnosed with amnestic MCI (n=138) were clustered based on baseline magnetic resonance imaging, cerebrospinal fluid, and serum biomarkers. The clusters were compared with respect to longitudinal atrophy, cognitive trajectory, and time to conversion.
RESULTS
Four clusters emerged with distinct biomarker patterns: The first cluster was biologically similar to normal controls and rarely converted to Alzheimer's disease (AD) during follow-up. The second cluster had characteristics of early Alzheimer's pathology. The third cluster showed the most severe atrophy but barely abnormal tau levels and a substantial proportion converted to clinical AD. The fourth cluster appeared to be pre-AD and nearly all converted to AD.
CONCLUSIONS
Subjects with MCI who were clinically similar showed substantial heterogeneity in biomarkers.
背景
先前对阿尔茨海默病神经影像倡议（ADNI）中的正常对照者进行的研究发现了显著的生物学异质性。我们推测，ADNI中的轻度认知障碍（MCI）受试者也会表现出异质性，并可能具有临床意义。
方法
根据基线磁共振成像、脑脊液和血清生物标志物，对诊断为遗忘型MCI的ADNI受试者（n = 138）进行聚类。比较各聚类在纵向萎缩、认知轨迹和转化时间方面的差异。
结果
出现了四个具有不同生物标志物模式的聚类：第一个聚类在生物学上与正常对照者相似，在随访期间很少转化为阿尔茨海默病（AD）。第二个聚类具有早期阿尔茨海默病病理学特征。第三个聚类显示出最严重的萎缩，但tau水平几乎没有异常，且很大一部分转化为临床AD。第四个聚类似乎处于AD前期，几乎全部转化为AD。
结论
临床症状相似的MCI受试者在生物标志物方面存在显著异质性。
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