Background and Objectives Previous studies reported that carriers of rare NOTCH3 variants comprised more than 10% of the general population and are susceptible to a heavy overall burden of cerebral small vessel disease while the injury patterns remain uncovered. This study aimed to investigate the imaging features in relation to rare NOTCH3 variants and the interaction between cortical atrophy and white matter lesions from a longitudinal view, with respect to spatial and dynamic patterns. Methods As part of a community-based cohort, we included participants with complete whole-exome sequencing and brain MRI in the baseline analysis. All participants were invited for a 5-year follow-up MRI, and those who did not complete the follow-up were excluded from the longitudinal analysis. NOTCH3 variants with minor allele frequency <1% in all 4 public population databases were defined as rare variants. We used general linear models to compare the volume of white matter hyperintensity (WMH) volum