Abstract Background and aims The association between lipid-lowering therapy (LLT) and cerebral microbleed (CMB) progression remains uncertain, particularly in middle-aged primary prevention populations. We examined the longitudinal relationship between LLT and CMB progression in a large Japanese brain health screening cohort. Methods We retrospectively analyzed adults with dyslipidemia and no prior stroke who underwent ≥2 brain MRI scans between January 2018 and December 2024. CMB burden was categorized by lesion count (0, 1, 2–5, 6–10, or ≥11). The primary outcome was CMB progression, defined as new CMBs or a shift to a higher CMB burden category. Secondary outcomes were progression of other cerebral small vessel disease (SVD) markers. We applied inverse probability of treatment weighting and Poisson regression to estimate adjusted incidence rate ratios (aIRR) and 3-year adjusted absolute risk differences. Results Of 65,454 screened individuals, 2,350 were included (median age 54 years; 42.8% women); 1,006 (42.8%) were LLT users. Over a median follow-up of 32.7 months, LLT use was associated with higher risk of CMB progression (aIRR 2.14; 95% CI, 1.07–4.30). LLT use was not associated with progression of white matter hyperintensities, perivascular spaces, or lacunes. The 3-year adjusted absolute risk differences for CMB progression was 0.70% (95% CI, 0.16%–1.74%). Conclusions In this Japanese primary prevention cohort, LLT was associated with CMB progression but not with other SVD markers. Although the absolute excess risk was small, individualized risk–benefit assessment may be warranted when prescribing LLT to middle-aged adults with dyslipidemia. Conflict of interest Dr. Ikeda, Dr. Yakushiji, Dr. Chiku, Dr. Tomimoto, and Dr. Ikawa report no disclosures. Ryuji Kawata is affiliated with the Department of Smart Brain Screening, EUCALIA, Inc.
Ikeda et al. (2026) studied this question.