Sex differences in the progression of cerebral microbleeds in patients with concomitant cerebral small vessel disease

Cindy W. Yoon, Joung Ho Rha, Hee Kwon Park, Soo Hyun Park, Soonwook Kwon, Byeong C. Kim, Young Chul Youn, Jee Hyang Jeong, Hyun Jeong Han, Seong Hye Choi

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Background and purpose: Sex differences in cerebral microbleeds (CMBs) are not well-known. We aimed to assess the impact of sex on the progression of CMBs. Methods: The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Out of 256 subjects, 189 participants with a follow-up brain scan were included in the analysis. The linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between men and women. Results: A total of 65 men and 124 women were analyzed. There were no significant differences in the prevalence (70.8 vs. 71.8%; P = 1.000) and the median [interquartile range (IQR)] number of total CMBs [1 (0–7) vs. 2 (0–7); P = 0.810] at baseline between men and women. The median (IQR) increase over 2 years in the number of CMBs was statistically higher in women than in men [1 (0–2) vs. 0 (0–1), P = 0.026]. The multivariate linear mixed-effects model showed that women had a significantly greater increase in the number of total, deep, and lobar CMBs compared to men after adjusting for age and the baseline number of CMBs [estimated log-transformed mean of difference between women and men: 0.040 (P = 0.028) for total CMBs, 0.037 (P = 0.047) for deep CMBs, and 0.047 (P = 0.009) for lobar CMBs]. Conclusion: The progression of CMB over 2 years was significantly greater in women than in men.

Original languageEnglish
Article number1054624
JournalFrontiers in Neurology
StatePublished - 20 Dec 2022

Bibliographical note

Funding Information:
This study was supported by grants from the National Research Council of Science and Technology (NST) Aging Convergence Research Center (CRC22011-600), the Institute of Information and Communications Technology Planning and Evaluation (IITP) (No. 2022-0-00448), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) (NRF-2020M3E5D2A01084721 and NRF-2018M3A9F1023697) funded by the Ministry of Science and ICT, Republic of Korea, from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and Korea Dementia Research Center (KDRC) funded by the Ministry of Health and Welfare and Ministry of Science and ICT, Republic of Korea (HU21C0016). This study received funding from the Korea Otsuka Pharmaceutical Company. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.

Publisher Copyright:
Copyright © 2022 Yoon, Rha, Park, Park, Kwon, Kim, Youn, Jeong, Han and Choi.


  • cerebral microbleeds
  • cerebral small vessel disease
  • microbleeds
  • sex differences
  • women


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