Mortality Outcomes in a Large Population with and without Covert Cerebrovascular Disease

Covert cerebrovascular disease (CCD) is frequently reported on neuroimaging and associates with increased dementia and stroke risk. We aimed to determine how incidentally-discovered CCD during clinical neuroimaging in a large population associates with mortality. We screened CT and MRI reports of adults aged ≥50 in the Kaiser Permanente Southern California health system who underwent neuroimaging for a non-stroke clinical indication from 2009-2019. Natural language processing identified incidental covert brain infarcts (CBI) and/or white matter hyperintensities (WMH), grading WMH as mild/moderate/severe. Models adjusted for age, sex, ethnicity, multimorbidity, vascular risks, depression, exercise, and imaging modality. Of n=241,028, the mean age was 64.9 (SD=10.4); mean follow-up 4.46 years; 178,554 (74.1%) had CT; 62,474 (25.9%) had MRI; 11,328 (4.7%) had CBI; and 69,927 (29.0%) had WMH. The mortality rate per 1,000 person-years with CBI was 59.0 (95%CI 57.0-61.1); with WMH=46.5 (45.7-47.2); with neither=17.4 (17.1-17.7). In adjusted models, mortality risk associated with CBI was modified by age, e.g. HR 1.34 [1.21-1.48] at age 56.1 years vs HR 1.22 [1.17-1.28] at age 72 years. Mortality associated with WMH was modified by both age and imaging modality e.g., WMH on MRI at age 56.1 HR = 1.26 [1.18-1.35]; WMH on MRI at age 72 HR 1.15 [1.09-1.21]; WMH on CT at age 56.1 HR 1.41 [1.33-1.50]; WMH on CT at age 72 HR 1.28 [1.24-1.32], vs. patients without CBI or without WMH, respectively. Increasing WMH severity associated with higher mortality, e.g. mild WMH on MRI had adjusted HR=1.13 [1.06-1.20] while severe WMH on CT had HR=1.45 [1.33-1.59]. Incidentally-detected CBI and WMH on population-based clinical neuroimaging can predict higher mortality rates. We need treatments and healthcare planning for individuals with CCD.