Yuto Uchida1,2, Hirohito Kan3, Keita Sakurai4, Nobuyuki Arai3, Shohei Inui5, Susumu Kobayashi6, Daisuke Kato1, Yoshino Ueki7, Noriyuki Matsukawa8. 1. Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 2. Department of Neurology, Toyokawa City Hospital, Aichi, Japan. 3. Department of Radiology, Nagoya City University Hospital, Nagoya, Japan. 4. Department of Radiology, Teikyo University School of Medicine, Tokyo, Japan. 5. Department of Radiology, The University of Tokyo Graduate School of Medicine School of Medicine Neuroscience, Tokyo, Japan. 6. Department of Radiology, Toyokawa City Hospital, Aichi, Japan. 7. Department of Rehabilitation Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 8. Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan norim@med.nagoya-cu.ac.jp.
Abstract
OBJECTIVE: To assess the relationship between 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 (DCE-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 subjects). 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 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.
OBJECTIVE: To assess the relationship between 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 (DCE-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 subjects). 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 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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