All MRI scans were obtained using 1.5T scanners (General Electric or Picker) producing 5-mm contiguous axial T1, T2, and proton density-weighted images. Infarcts were identified and defined by size and location on T2 and proton density-weighted images. Consistent with recent CSVD research recommendations [10 (link)] and previous ARIC investigations [7 (link), 8 (link)], “smaller infarcts” were defined as those <3mm on right-to-left or anterior-to-posterior size and “larger infarcts” were defined as those ≥3mm but <20mm. Care was taken to distinguish smaller infarcts from perivascular spaces by considering absence of mass effect and hyperintensity to gray matter. Late midlife infarct burden was categorized as presence of smaller infarcts only (n=50), presence of larger infarcts only (n=185), presence of both (n=35), or infarct-free (n=1611). Consideration of count of infarcts was only possible for “larger infarcts” and was tabulated as either “Single Larger Infarct” or “Multiple Larger Infarcts” (≥2). In a sensitivity model to consider multi-infarct burden, we used six infarct exposure groups: [infarct-free (referent; n=1611), smaller only (n=50), single larger (n=129), multiple larger (n=56), smaller + single larger (n=17), and smaller + multiple larger (n=18)]. All infarcts were considered subclinical as no participant in the current study had a prevalent stroke history.