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Published on: May 23, 2016
Iron leakage owing to blood-brain barrier disruption in small vessel disease CADASIL
Yuto Uchida1, Hirohito Kan1, Keita Sakurai1
1From 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.
Insights
Cerebral iron accumulation in CADASIL patients correlates with blood-brain barrier damage and cognitive decline. These findings suggest imaging techniques can help monitor small vessel disease progression.
Area of Science:
- Neurology
- Neuroimaging
- Small Vessel Disease
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic small vessel disease.
- Iron accumulation and blood-brain barrier (BBB) dysfunction are implicated in CADASIL pathogenesis.
- The relationship between iron deposition, BBB integrity, and cognitive impairment in CADASIL requires further elucidation.
Purpose of the Study:
- To investigate the association between iron accumulation, BBB damage, and cognitive function in patients with CADASIL.
- To explore the utility of quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced MRI in assessing these parameters.
Main Methods:
- Cross-sectional study involving 21 CADASIL patients (with NOTCH3 mutations) and 21 healthy controls.
- Brain MRI including QSM for iron deposition and dynamic contrast-enhanced MRI for BBB permeability.
- Global physical and cognitive assessments, including Montreal Cognitive Assessment (MoCA) scores.
Main Results:
- Symptomatic CADASIL patients showed significantly lower MoCA scores than asymptomatic patients and controls.
- Increased iron deposition (higher QSM values) was observed in the symptomatic group in specific brain regions.
- Iron deposition positively correlated with regional BBB permeability and negatively with MoCA scores.
Conclusions:
- Cerebral iron burden is linked to regional BBB permeability and cognitive dysfunction in CADASIL.
- QSM and dynamic contrast-enhanced MRI show potential as auxiliary biomarkers for monitoring CADASIL progression.
- Understanding these relationships can aid in managing small vessel diseases like CADASIL.
Objective:
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).
Methods:
We enrolled 21 patients with NOTCH3 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.
Results:
Among 21 NOTCH3 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: r = 0.57, p = 0.006; caudate nucleus: r = 0.51, p = 0.019; temporal pole: r = 0.48, p = 0.030; centrum semiovale: r = 0.45, p = 0.044) and negatively correlated with Montreal Cognitive Assessment scores (caudate nucleus: r = -0.53, p = 0.012; temporal pole: r = -0.56, p = 0.008).
Conclusions:
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.
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