Abstract

Background: White matter disease (WMD) and silent brain infarction (SBI) are known to be risk markers for dementia. Nevertheless, the effects of incidentally-discovered WMD and SBI on routinely-obtained neuroimages is unknown. Methods: In the retrospective cohort study, Kaiser Permanente-Southern California (KPSC) health plan enrollees aged ≥ 50 years old with a brain cross-sectional image (CT or MRI) between 2009-2019 and without a prior history of ischemic stroke, transient ischemic attack, or dementia were identified. Natural language processing (NLP) was used to identify patients with SBI and WMD on the first qualifying neuroimaging report. Cox proportional hazards regression model was applied to estimate the effects of WMD and SBI on dementia, controlling for major cardiovascular risk factors. Results: Among 262,875 individuals receiving brain neuroimaging, 13,154 (5.0%) and 78,330 (29.8%) had SBI and WMD, respectively. The table below summarizes the crude dementia incidence rates. The crude hazard ratio (HR) was 3.69 (95% CI 3.58-3.80) for WMD and 2.80 (95% CI 2.68-2.93) for SBI. In the multivariable model controlling for all major cardiovascular risk factors, the effect of WMD on dementia risk was found to be stronger in younger compared to older patients and for CT- compared to MRI-discovered lesions. With CT, the adjusted HR was 3.08 (95% CI 2.84-3.34) for those < age 70 and 1.90 (95% CI 1.83-1.97) for those ≥ age 70. With MRI, the adjusted HR was 2.58 (95% CI 2.31-2.87) for those < age 70 and 1.59 (95% CI 1.45-1.75) for those ≥ age 70. The adjusted HR associated with a finding of SBI was 2.01 (95% CI 1.78-2.32) for patients age <70 and 1.26 (95% CI 1.20-1.32) for patients age ≥70, and was not modified by imaging modality. Conclusion: Incidentally-discovered WMD and SBI are common in patients ≥ age 50 and are associated with substantial increase in the risk of subsequent dementia. The findings may represent an opportunity for dementia prevention.

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