Supplementary Material for: Dose-dependent Effect of Current Smoking on Enlarged Perivascular Space Identified on Brain MRI

Introduction: Cerebral small-vessel disease (CSVD) is a common cause of cognitive decline and stroke. Several studies have shown that smoking is a risk factor for CSVD progression. However, the extent to which smoking exacerbates CSVD lesions remains unclear. In this study, we aimed to clarify the association between total smoking exposure and the severity of CSVD in healthy participants. Methods: We analyzed the data of participants aged ≥ 50 years who underwent brain screening. The participants’ age, sex, body mass index, alcohol consumption history, and medical history (hypertension, diabetes mellitus, and dyslipidemia) were investigated. Smoking status was assessed in pack-years, and smokers were classified as current or past smokers. CSVD findings on magnetic resonance imaging were used to evaluate the severity of periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), and enlarged perivascular spaces (EPVSs). The EPVSs were measured in the basal ganglia and centrum semiovale regions. Multivariable ordinal logistic regression analyses were performed to evaluate the effect of smoking, adjusted for the participants’ baseline characteristics. Results: A total of 2,137 participants were included in this study. The mean age of the participants was 58.7 years. The mean pack-years were 20.5 for past smokers and 26.8 for current smokers. Among current smokers, increased pack-years were significantly associated with a high EPVS burden in the basal ganglia (odds ratio: 1.14, 95% confidence interval: 1.00–1.28), whereas no such significant association was found for past smokers. No statistically significant association was found between pack-years and the risks of PVH, DSWMH, or EPVS in the centrum semiovale. Conclusion: Current smoking was associated with a dose-dependent risk of EPVS in the basal ganglia in healthy participants.