From the Departments of Neurology and Neuroscience (Y. Uchida, D.K., N.M.) and Rehabilitation Medicine (Y. Ueki), Nagoya City University Graduate School of Medical Sciences; Departments of Neurology (Y. Uchida) and Radiology (S.K.), Toyokawa City Hospital, Aichi; Department of Radiology (H.K., N.A.), Nagoya City University Hospital; Department of Radiology (K.S.), Teikyo University School of Medicine; and Department of Radiology (S.I.), Neuroscience, School of Medicine, The University of Tokyo Graduate School of Medicine, Japan.
Neurology. 2020 Sep 1;95(9):e1188-e1198. doi: 10.1212/WNL.0000000000010148. Epub 2020 Jun 25.
To assess the relationship among iron accumulation, blood-brain barrier (BBB) damage, and cognitive function in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
We enrolled 21 patients with mutations and 21 age-matched healthy controls in this cross-sectional study. All participants underwent global physical and cognitive assessments and brain MRI using voxel-based quantitative susceptibility mapping (QSM; iron deposition measure) and dynamic contrast-enhanced MRI (BBB permeability measure). We compared behavioral and imaging data between the groups and analyzed the correlations in each group.
Among 21 mutation carriers, 10 were symptomatic and 11 asymptomatic. Montreal Cognitive Assessment scores were significantly different among the groups (symptomatic < asymptomatic < control participants). Voxel-based QSM analysis revealed that the symptomatic group had higher QSM values than did the asymptomatic group in the putamen, caudate nucleus, temporal pole, and centrum semiovale. These QSM values were positively correlated with regional BBB permeabilities (putamen: = 0.57, = 0.006; caudate nucleus: = 0.51, = 0.019; temporal pole: = 0.48, = 0.030; centrum semiovale: = 0.45, = 0.044) and negatively correlated with Montreal Cognitive Assessment scores (caudate nucleus: = -0.53, = 0.012; temporal pole: = -0.56, = 0.008).
This study showed that cerebral iron burden was associated with regional BBB permeability and cognitive dysfunction in patients with CADASIL, highlighting the potential of these imaging techniques as auxiliary biomarkers to monitor the course of small vessel disease.
评估脑常染色体显性动脉病伴皮质下梗死和白质脑病（CADASIL）患者铁蓄积、血脑屏障（BBB）损伤与认知功能之间的关系。
本横断面研究纳入了 21 名携带 突变的患者和 21 名年龄匹配的健康对照者。所有参与者均接受了全身体格检查和认知评估，以及脑磁共振成像（MRI）检查，包括基于体素的定量磁化率（铁沉积指标）和动态对比增强 MRI（BBB 通透性指标）。我们比较了两组之间的行为学和影像学数据，并分析了每组中的相关性。
在 21 名 突变携带者中，10 名有症状，11 名无症状。蒙特利尔认知评估量表（MoCA）评分在各组间差异有统计学意义（有症状者＜无症状者＜对照组）。基于体素的 QSM 分析显示，与无症状组相比，有症状组的壳核、尾状核、颞极和半卵圆中心的 QSM 值更高。这些 QSM 值与区域 BBB 通透性呈正相关（壳核： = 0.57， = 0.006；尾状核： = 0.51， = 0.019；颞极： = 0.48， = 0.030；半卵圆中心： = 0.45， = 0.044），与 MoCA 评分呈负相关（尾状核： = -0.53， = 0.012；颞极： = -0.56， = 0.008）。
本研究表明，CADASIL 患者脑铁负荷与局部 BBB 通透性和认知功能障碍有关，提示这些影像学技术有可能成为监测小血管疾病进程的辅助生物标志物。
