Strategic role of frontal white matter tracts in vascular cognitive impairment: a voxel-based lesion-symptom mapping study in CADASIL
Strategic role of frontal white matter tracts in vascular cognitive impairment: a voxel-based lesion-symptom mapping study in CADASIL
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DOI：
10.1093/brain/awr169
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发表时间：
2011-08-01
期刊：
影响因子：
14.5
通讯作者：
Dichgans, Martin
中科院分区：
文献类型：
--
作者：
Duering, Marco;Zieren, Nikola;Dichgans, Martin
脑小血管疾病是血管性认知障碍的最常见原因。它通常表现为腔隙性梗死和缺血性白质病变。然而，人们对这些病变与认知症状之间的关系知之甚少。先前的研究发现，缺血性病变的负担与认知症状之间的相关性较差，因此认知表现的大部分差异无法解释。本研究的目的是探讨小血管疾病中皮质下缺血性病变的位置与认知症状之间的关系。我们对 215 名 CADASIL 患者的数据应用了基于体素的病变症状映射方法，CADASIL 是一种基因定义的小血管疾病，具有 NOTCH3 基因突变。所有患者均接受磁共振成像和综合神经心理学测试。腔隙病变和白质病变分别在三维 T-1 和流体衰减反转恢复序列上进行分割。 145 名受试者总共有 854 个腔隙性病变（每人 1-13 个）。白质高信号标准化体积范围为颅内腔的 0.0425% 至 21.5%。腔隙性病变和白质高信号均检测到认知表现的显着集群。最突出的结果是在处理速度的复合评分上获得的，处理速度是这组患者中主要受影响的认知领域。战略位置包括丘脑前部、内囊膝部和前肢、放射冠前部和胼胝体膝部。通过将病变症状映射数据与来自概率白质图谱的信息相结合，我们发现大多数处理速度簇投射在前丘脑辐射和小镊子上。在包括人口统计参数、脑萎缩和缺血性病变体积的多变量模型中，腔隙性病变的区域体积和丘脑前部辐射中的白质高信号预测了处理速度任务的表现，而缺血性病变的整体体积没有独立的贡献。这些观察结果强调了病变定位对于腔隙性和缺血性白质病变的重要性。我们的研究结果进一步强调了丘脑前部辐射是影响处理速度的主要解剖结构。这些发现共同为额叶皮质下回路在脑小血管疾病和血管性认知障碍中的核心作用提供了强有力的支持。
Cerebral small vessel disease is the most common cause of vascular cognitive impairment. It typically manifests with lacunar infarcts and ischaemic white matter lesions. However, little is known about how these lesions relate to the cognitive symptoms. Previous studies have found a poor correlation between the burden of ischaemic lesions and cognitive symptoms, thus leaving much of the variance in cognitive performance unexplained. The objective of the current study was to investigate the relationship between the location of subcortical ischaemic lesions and cognitive symptoms in small vessel disease. We applied a voxel-based lesion-symptom mapping approach to data from 215 patients with CADASIL, a genetically defined small vessel disease with mutations in the NOTCH3 gene. All patients were examined by magnetic resonance imaging and comprehensive neuropsychological testing. Lacunar lesions and white matter lesions were segmented on three-dimensional T-1 and fluid-attenuated inversion recovery sequences, respectively. One hundred and forty-five subjects had a total of 854 lacunar lesions (range 1-13 per individual). The normalized volume of white matter hyperintensities ranged from 0.0425% to 21.5% of the intracranial cavity. Significant clusters for cognitive performance were detected for both lacunar lesions and white matter hyperintensities. The most prominent results were obtained on a compound score for processing speed, the predominantly affected cognitive domain in this group of patients. Strategic locations included the anterior parts of the thalamus, the genu and anterior limb of the internal capsule, the anterior corona radiata and the genu of the corpus callosum. By combining the lesion-symptom mapping data with information from a probabilistic white matter atlas we found that the majority of the processing speed clusters projected on the anterior thalamic radiation and the forceps minor. In multivariate models that included demographic parameters, brain atrophy and the volume of ischaemic lesions, regional volumes of lacunar lesions and white matter hyperintensities in the anterior thalamic radiation predicted performance in processing speed tasks, whereas there was no independent contribution of the global volume of ischaemic lesions. These observations emphasize the importance of lesion location for both lacunar and ischaemic white matter lesions. Our findings further highlight the anterior thalamic radiation as a major anatomical structure impacting on processing speed. Together these findings provide strong support for a central role of frontal-subcortical circuits in cerebral small vessel disease and vascular cognitive impairment.