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Abstract
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.
Glossary
- AIF=
- arterial input function;
- ANCOVA=
- analysis of covariance;
- BBB=
- blood–brain barrier;
- BDI-II=
- Beck Depression Inventory–II;
- CADASIL=
- cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy;
- CCA=
- common carotid artery;
- CI=
- confidence interval;
- DCE-MRI=
- dynamic contrast-enhanced MRI;
- FA=
- flip angle;
- FLAIR=
- fluid-attenuated inversion recovery;
- FOV=
- field of view;
- GM=
- gray matter;
- Hct=
- hematocrit;
- MC=
- mutation carrier;
- MoCA=
- Montreal Cognitive Assessment;
- MP-QSM=
- magnetization-prepared spoiled turbo multiple gradient echo sequence with inversion pulse for quantitative susceptibility mapping;
- mRS=
- modified Rankin Scale;
- NA=
- not applicable;
- QSM=
- quantitative susceptibility mapping;
- ROI=
- region of interest;
- TE=
- echo time;
- TI=
- inversion time;
- TMT=
- Trail-Making Test;
- TR=
- repetition time;
- WM=
- white matter
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received August 21, 2019.
- Accepted in final form March 2, 2020.
- © 2020 American Academy of Neurology
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