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Effect of corticosubcortical iron deposition on dysfunction in CADASIL is mediated by white matter microstructural
Xiuqin Jia1, Yingying Li2, Yunqing Ying3
1Department 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.
Insights
Iron accumulation in the brain affects cognitive function in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). White matter changes mediate this relationship, impacting memory and executive functions.
Area of Science:
- Neuroscience
- Neurology
- Radiology
Background:
- Iron dysregulation is implicated in cognitive decline in CADASIL.
- Pathophysiological mechanisms, particularly the role of white matter changes, are not fully understood.
Purpose of the Study:
- To investigate the relationship between iron deposition, white matter microstructural changes, and cognitive deficits in CADASIL.
- To explore whether white matter changes mediate the effects of iron on cognition.
Main Methods:
- Genetic confirmation of 30 CADASIL patients and 30 healthy controls.
- Multimodal MRI (Quantitative Susceptibility Mapping, PSMD) and neuropsychological assessments.
- Mediation effect analysis to examine interrelationships.
Main Results:
- CADASIL patients showed cognitive decline, primarily in memory and executive function.
- Excessive iron deposition was observed in the temporal-precuneus pathway and deep gray matter.
- Peak width of skeletonized mean diffusivity (PSMD) mediated the association between iron concentration and cognitive profile.
Conclusions:
- Iron deposition in specific brain pathways contributes to selective cognitive decline in CADASIL.
- White matter microstructural changes act as a mediator between iron concentration and cognitive impairment.
Abstract:
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.
