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Blood\u2013brain barrier (BBB) failure has been hypothesized in the pathophysiology of CSVD. However, it is unclear whether there is BBB damage in the two types of hereditary CSVD, especially in heterozygous HTRA1 mutation-related CSVD.<\/jats:p>\n               <jats:p>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 controls (n = 24). All participants underwent clinical cognitive assessments and brain MRI. Diffusion-prepared pseudo-continuous arterial spin labelling was used to estimate the water exchange rate across the BBB (kw). Correlation and multiple linear regression analyses were used to examine the association between kw and disease burden and neuropsychological performance, respectively.<\/jats:p>\n               <jats:p>Compared with the healthy controls, kw in the whole brain and multiple brain regions was decreased in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients (Bonferroni-corrected P &amp;lt; 0.007). In the CADASIL group, decreased kw in the whole brain (\u03b2 = \u22120.634, P = 0.001), normal-appearing white matter (\u03b2 = \u22120.599, P = 0.002) and temporal lobe (\u03b2 = \u22120.654, P = 0.001) was significantly associated with higher CSVD score after adjusting for age and sex. Reduced kw in the whole brain was significantly associated with poorer neuropsychological performance after adjusting for age, sex and education in both CADASIL and heterozygous HTRA1 mutation-related CSVD groups (\u03b2 = 0.458, P = 0.001; \u03b2 = 0.884, P = 0.008).<\/jats:p>\n               <jats:p>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 types of 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.<\/jats:p>","DOI":"10.1093\/brain\/awac500","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T16:03:22Z","timestamp":1673366602000},"page":"3079-3087","source":"Crossref","is-referenced-by-count":56,"title":["Decreased water exchange rate across blood\u2013brain barrier in hereditary cerebral small vessel disease"],"prefix":"10.1093","volume":"146","author":[{"given":"Yingying","family":"Li","sequence":"first","affiliation":[{"name":"Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University , Beijing 100020 , China"},{"name":"Key Lab of Medical Engineering for Cardiovascular Disease, Ministry of Education , Beijing 100020 , 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