Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; Key Lab of Medical Engineering for Cardiovascular Disease, Ministry of Education, Beijing 100020, China.
Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Neuroimage Clin. 2023;39:103485. doi: 10.1016/j.nicl.2023.103485. Epub 2023 Jul 27.
Iron dysregulation may attenuate cognitive performance in patients with CADASIL. However, the underlying pathophysiological mechanisms remain incompletely understood. Whether white matter microstructural changes mediate these processes is largely unclear. In the present study, 30 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients were confirmed via genetic analysis and 30 sex- and age-matched healthy controls underwent multimodal MRI examinations and neuropsychological assessments. Quantitative susceptibility mapping and peak width of skeletonized mean diffusivity (PSMD) were analyzed. Mediation effect analysis was performed to explore the interrelationship between iron deposition, white matter microstructural changes and cognitive deficits in CADASIL. Cognitive deterioration was most affected in memory and executive function, followed by attention and working memory in CADASIL. Excessive iron in the temporal-precuneus pathway and deep gray matter specific to CADASIL were identified. Mediation analysis further revealed that PSMD mediated the relationship between iron concentration and cognitive profile in CADASIL. The present findings provide a new perspective on iron deposition in the corticosubcortical circuit and its contribution to disease-related selective cognitive decline, in which iron concentration may affect cognition by white matter microstructural changes in CADASIL.
铁代谢失调可能会削弱 CADASIL 患者的认知表现。然而，其潜在的病理生理机制仍不完全清楚。脑白质微观结构的变化是否介导了这些过程尚不清楚。在本研究中，通过基因分析证实了 30 名脑常染色体显性遗传性动脉病伴皮质下梗死和白质脑病（CADASIL）患者，对 30 名性别和年龄匹配的健康对照进行了多模态 MRI 检查和神经心理学评估。分析了定量磁化率和骨架平均弥散峰宽（PSMD）。采用中介效应分析探讨了 CADASIL 中铁沉积、脑白质微观结构变化与认知缺陷之间的相互关系。在 CADASIL 中，认知功能恶化受记忆力和执行功能的影响最大，其次是注意力和工作记忆。确定了与 CADASIL 相关的颞顶叶-扣带回通路和深部灰质的铁过量。中介分析进一步表明，PSMD 介导了 CADASIL 中脑铁浓度与认知特征之间的关系。本研究结果为皮质下脑区皮质环路中铁沉积及其对与疾病相关的选择性认知下降的贡献提供了新的视角，其中铁浓度可能通过 CADASIL 中的脑白质微观结构变化影响认知。
