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Development of Parkinson's disease and its relationship with incidentally-discovered white matter disease and covert brain infarction in a real world cohort

Importance: While a link between cerebrovascular disease and cerebrovascular risk factors and subsequent development of Parkinson's disease has been suggested, the association between covert cerebrovascular disease and subsequent Parkinson's disease has not been rigorously examined. Objective: To examine the relationship between covert cerebrovascular disease, comprised of covert brain infarction and white matter disease, discovered incidentally in routine care and subsequent Parkinson's disease. Design: Enrollment in this observational cohort study occurred between 2009 and 2019. Setting: Kaiser Permanente Southern California health system. Participants: Patients were 50 years or older and received neuroimaging for a non-stroke indication. Exposure: Incidental covert brain infarction and white matter disease identified by natural language processing of neuroimaging reports. Natural language processing also classified white matter disease severity. Main Outcomes: Parkinson's disease. Results: 230,062 patients were included with a total of 980,772 person-years of follow-up and a median follow-up time of 3.72 years. 1,941 cases of Parkinson's disease were identified, with a median time-to-event of 2.35 (IQR 0.90 to 4.58) years. Covert cerebrovascular disease was identified in 70,592 (30.68%) patients, 10,622 (4.62%) with covert brain infarction and 65,814 (28.61%) with white matter disease. After adjustment for known risk factors, white matter disease was found to be associated with Parkinson's disease, with an adjusted hazard ratio of 1.67 (1.44, 1.93) for patients <70 years and 1.33 (1.18, 1.50) for those 70 years or older. Greater severity of white matter disease was associated with an increased incidence of Parkinson's disease per 1000 person-years, from 1.52 (1.43, 1.61) in patients without white matter disease to 4.90 (3.86, 6.13) in those with severe white matter disease. Findings were robust when more specific definitions of Parkinson's disease were used. Covert brain infarction was not associated with Parkinson's disease (adjusted hazard ratio=1.05 [0.88, 1.24]). Conclusions and Relevance: White matter disease was associated with subsequent Parkinson's disease, an association strengthened with younger age and increased white matter disease severity. Covert brain infarction did not appear to be associated with subsequent Parkinson's disease.