Authors’ reply to: ‘high-risk carotid plaque and cognition: cerebral small vessel disease, statin intensity, and the asymptomatic paradox’

We thank Dr Lu et al. for their insightful comments1 on our recent work from the CAMP study.2 Their letter highlights three important aspects—the burden of cerebral small vessel disease (SVD), the intensity of lipid-lowering therapy, and the definition of asymptomatic status—that deserve careful consideration. We agree that SVD may contribute to cognitive decline,3 and could potentially influence the interpretation of our findings. While the original analysis did not specifically address the relationship between SVD burden and cognitive performance, we performed additional exploratory analysis stratifying patients into no/mild SVD (absence of SVD or white matter hyperintensities graded as Fazekas 0–1 without lacunar infarcts) and moderate-to-severe SVD (presence of lacunar infarcts and/or white matter hyperintensities graded Fazekas 2–3). Visuospatial performance was assessed using a composite score derived from standardized neuropsychological tests of visuospatial function (Rey–Osterrieth Complex Figure copy and Clock Drawing Test). Visuospatial performance did not significantly differ across SVD strata in multivariable linear regression analyses adjusted for age, sex, and education (β = 0.147, 95% CI −0.143 to 0.437, P = 0.318). Importantly, we further assessed whether SVD burden influenced the association between high-risk plaque features and cognitive performance. After adjustment for SVD burden, the association between high-risk plaque features and cognitive outcomes remained non-significant (β = −0.017, 95% CI −0.269 to 0.234, P = 0.892), indicating that SVD is unlikely to explain the lack of association observed in the main analysis.