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Decreased water exchange rate across blood-brain barrier in hereditary cerebral small vessel disease

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机构： [1]Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. [2]Key Lab of Medical Engineering for Cardiovascular Disease, Ministry of Education, Beijing, 100020, China. [3]Department of Neurology, National Center for Neurological Disorders, National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China. [4]Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disorders, Beijing, 100053, China. [5]State Key Laboratory of Brain and Cognitive Science, Beijing MRI Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. [6]Department of Radiology, Huashan Hospital, Fudan University, Shanghai, 200040, China. [7]Laboratory of FMRI Technology (LOFT), USC Mark & Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90007, USA. [8]Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beijing, 100020, China.

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关键词： CADASIL heterozygous HTRA1 mutation related CSVD blood–brain barrier magnetic resonance imaging water exchange rate (kw)

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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and heterozygous HTRA1 mutation related cerebral small vessel disease (CSVD) are the two types of dominant hereditary CSVD. Blood-brain barrier (BBB) failure has been hypothesized in the pathophysiology of CSVD. However, it is unclear whether there are BBB damage in the two hereditary CSVD, especially in heterozygous HTRA1 mutation related CSVD. In this study, a case control design was used with two disease groups including CADASIL (n = 24), heterozygous HTRA1 mutation related CSVD (n = 9), and healthy control (n = 24) were studied. All participants underwent clinical cognitive assessments and brain MRI. Diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) was used to estimate water exchange rate across the BBB (kw). Correlation and multiple linear regression analysis were used to examine the association between kw and disease burden and neuropsychological performance respectively. Compared with healthy control, kw in the whole brain and multiple brain regions was decreased in both CADASIL and heterozygous HTRA1 mutation related CSVD patients (Bonferroni corrected p < 0.007). In the CADASIL group, decreased kw in the whole brain (β = -0.634, p = 0.001), normal-appearing white matter (NAWM) (β = -0.599, p = 0.002), and temporal lobe (β = -0.654, p = 0.001) was significantly associated with higher CSVD score after adjusting age and sex. Reduced kw in the whole brain was significantly associated with poorer neuropsychological performance after adjusting age, sex, and education in both CADASIL and heterozygous HTRA1 mutation related CSVD group (β = 0.458, p = 0.001; β = 0.884, p = 0.008). This study showed that there was decreased water exchange rate across the BBB in both CADASIL and heterozygous HTRA1 mutation related CSVD patients, suggesting a common pathophysiological mechanism underlying the two hereditary CSVD. These results highlight the potential use of kw for monitoring the course of CADASIL and heterozygous HTRA1 mutation related CSVD, a possibility which should be tested in future research.© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区临床神经病学 1 区神经科学

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区临床神经病学 1 区神经科学

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出版当年[2021]版：

Q1 CLINICAL NEUROLOGY Q1 NEUROSCIENCES

最新[2023]版：

Q1 CLINICAL NEUROLOGY Q1 NEUROSCIENCES

影响因子： 11.9 最新[2023版] 13.3 最新五年平均 15.255 出版当年[2021版] 16.173 出版当年五年平均 13.501 出版前一年[2020版] 14.5 出版后一年[2022版]

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第一作者机构： [1]Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. [2]Key Lab of Medical Engineering for Cardiovascular Disease, Ministry of Education, Beijing, 100020, China.

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通讯作者：

通讯机构： [1]Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. [2]Key Lab of Medical Engineering for Cardiovascular Disease, Ministry of Education, Beijing, 100020, China. [3]Department of Neurology, National Center for Neurological Disorders, National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China. [4]Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disorders, Beijing, 100053, China. [8]Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beijing, 100020, China. [*1]Department of Neurology, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Road, Xicheng District, Beijing 100053, China [*2]Department of Neurology, Huashan Hospital, Fudan University, No. 12 Wulumuqizhong Road,Jingan District, Shanghai 200040, China [*3]Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongti South Road, Chaoyang District, Beijing 100020, China

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Decreased water exchange rate across blood-brain barrier in hereditary cerebral small vessel disease