Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau- Biomedical Research Institute Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Spain.
Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau- Biomedical Research Institute Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Spain; Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain.
Alzheimers Dement. 2017 May;13(5):499-509. doi: 10.1016/j.jalz.2016.08.010. Epub 2016 Sep 28.
Brain structural changes in preclinical Alzheimer's disease (AD) are poorly understood.
We compared the changes in cortical thickness in the ADNI cohort during a 2-year follow-up between the NIA-AA preclinical AD stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed the correlation between baseline CSF biomarkers and cortical atrophy rates.
At follow-up, stage 1 subjects showed reduced atrophy rates in medial frontal areas and precuneus compared to stage 0 subjects, whereas stage 2/3 subjects presented accelerated atrophy in medial temporal structures. Low CSF Aβ levels were associated with reduced atrophy rates in subjects with normal tau levels and high CSF tau levels with accelerated atrophy only in subjects with low Aβ levels.
Our longitudinal data confirm a biphasic trajectory of changes in brain structure in preclinical AD. These have implications in AD trials, both in patient selection and the use of MRI as a surrogate marker of efficacy.
在临床前阿尔茨海默病（AD）中，大脑结构的变化尚未得到很好的理解。
我们比较了 ADNI 队列中，根据脑脊液（CSF）生物标志物水平定义的 NIA-AA 临床前 AD 阶段，在 2 年随访期间皮质厚度的变化。我们还分析了基线 CSF 生物标志物与皮质萎缩率之间的相关性。
在随访时，与阶段 0 受试者相比，阶段 1 受试者的内侧额区和楔前叶的萎缩率降低，而阶段 2/3 受试者的内侧颞叶结构的萎缩率加快。CSF Aβ 水平较低与正常 tau 水平的受试者的萎缩率降低相关，而高 CSF tau 水平仅与低 Aβ 水平的受试者的萎缩率加快相关。
我们的纵向数据证实了临床前 AD 中大脑结构变化的双相轨迹。这对 AD 试验具有影响，包括在患者选择和使用 MRI 作为疗效替代标志物方面。
