Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients.
Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients.
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DOI：
10.3389/fnagi.2017.00038
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发表时间：
2017
影响因子：
4.8
通讯作者：
Leh SE
中科院分区：
文献类型：
--
作者：
Kälin AM;Park MT;Chakravarty MM;Lerch JP;Michels L;Schroeder C;Broicher SD;Kollias S;Nitsch RM;Gietl AF;Unschuld PG;Hock C;Leh SE
未来治疗的效果取决于生物标志物，这些生物标志物可以识别患有轻度认知障碍的患者最有可能转变为阿尔茨海默病的风险。在这里，我们应用最近开发的分析技术来调查稳定型轻度认知障碍（MCI）患者（n = 23，年龄范围 59-82，47.8% 女性）、未来转换者在基线（n = 10，年龄范围 66-84，90% 女性）和转换时（年龄范围 68-87）与分组年龄和性别匹配的健康对照受试者（n = 23，年龄范围 61-81，47.8% 女性；n = 10，年龄范围 66-82，80% 女性；n = 10，年龄范围 68-82，70% 女性）。此外，我们研究了皮质变薄以及海马萎缩的整体和局部测量，作为阿尔茨海默病的已知关键成像标志物。除了双侧纹状体体积减少外，认知稳定的患者没有发现形态变化。相比之下，我们在基线和转换时确定了未来转换器中纹状体和丘脑区域的形状变化。这些形状改变与阿尔茨海默病类似，未来转换者在基线时左半球形态变化（内侧颞区皮质变薄、海马总和亚区萎缩），在转换时进展为类似的右半球改变。此外，接受者操作特征曲线分析表明，在基线识别未来转化者方面，皮质下形状改变可能优于海马体积。这些结果进一步证实了早期皮质变薄和海马萎缩在阿尔茨海默病早期检测中的关键作用。但首先也是最重要的是，通过将未来的转化者（而不是具有稳定认知能力的患者）与认知正常的受试者区分开来，我们的结果支持了早期皮质下形状改变和海马亚区体积减少作为早期检测阿尔茨海默病的潜在标志物的价值。
Efficacy of future treatments depends on biomarkers identifying patients with mild cognitive impairment at highest risk for transitioning to Alzheimer's disease. Here, we applied recently developed analysis techniques to investigate cross-sectional differences in subcortical shape and volume alterations in patients with stable mild cognitive impairment (MCI) (n = 23, age range 59–82, 47.8% female), future converters at baseline (n = 10, age range 66–84, 90% female) and at time of conversion (age range 68–87) compared to group-wise age and gender matched healthy control subjects (n = 23, age range 61–81, 47.8% female; n = 10, age range 66–82, 80% female; n = 10, age range 68–82, 70% female). Additionally, we studied cortical thinning and global and local measures of hippocampal atrophy as known key imaging markers for Alzheimer's disease. Apart from bilateral striatal volume reductions, no morphometric alterations were found in cognitively stable patients. In contrast, we identified shape alterations in striatal and thalamic regions in future converters at baseline and at time of conversion. These shape alterations were paralleled by Alzheimer's disease like patterns of left hemispheric morphometric changes (cortical thinning in medial temporal regions, hippocampal total and subfield atrophy) in future converters at baseline with progression to similar right hemispheric alterations at time of conversion. Additionally, receiver operating characteristic curve analysis indicated that subcortical shape alterations may outperform hippocampal volume in identifying future converters at baseline. These results further confirm the key role of early cortical thinning and hippocampal atrophy in the early detection of Alzheimer's disease. But first and foremost, and by distinguishing future converters but not patients with stable cognitive abilities from cognitively normal subjects, our results support the value of early subcortical shape alterations and reduced hippocampal subfield volumes as potential markers for the early detection of Alzheimer's disease.