Noyce, Alastair J

Objective This study aimed 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 disease. Methods Patients were ≥50 years and received neuroimaging for non‐stroke indications in the Kaiser Permanente Southern California system from 2009 to 2019. Natural language processing identified incidentally discovered covert brain infarction and white matter disease and classified white matter disease severity. The Parkinson disease outcome was defined as 2 ICD diagnosis codes. Results 230,062 patients were included (median follow‐up 3.72 years). A total of 1,941 Parkinson disease cases were identified (median time‐to‐event 2.35 years). Natural language processing identified covert cerebrovascular disease in 70,592 (30.7%) patients, 10,622 (4.6%) with covert brain infarction and 65,814 (28.6%) with white matter disease. After adjustment for known risk factors, white matter disease was associated with Parkinson disease (hazard ratio 1.67 [95%CI, 1.44, 1.93] for patients <70 years and 1.33 [1.18, 1.50] for those ≥70 years). Greater severity of white matter disease was associated with increased incidence of Parkinson disease(/1,000 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 disease. Findings were robust when more specific definitions of Parkinson disease were used. Covert brain infarction was not associated with Parkinson disease (adjusted hazard ratio = 1.05 [0.88, 1.24]). Interpretation Incidentally discovered white matter disease was associated with subsequent Parkinson disease, an association strengthened with younger age and increased white matter disease severity. Incidentally discovered covert brain infarction did not appear to be associated with subsequent Parkinson disease. ANN NEUROL 2022;92:620–630

Parkinson’s disease (PD) is thought to be caused by a combination of genetic and environmental factors. Bacterial or viral infection has been proposed as a potential risk factor, and there is supporting although not entirely consistent epidemiologic and basic science evidence to support its role. Encephalitis caused by influenza has included parkinsonian features. Epidemiological evidence is most compelling for an association between PD and hepatitis C virus. Infection with Helicobacter pylori may be associated not only with PD risk but also response to levodopa. Rapidly evolving knowledge regarding the role of the microbiome also suggests a role of resident bacteria in PD risk. Biological plausibility for the role for infectious agents is supported by the known neurotropic effects of specific viruses, particular vulnerability of the substantia nigra and even the promotion of aggregation of alpha-synuclein. A common feature of implicated viruses appears to be production of high levels of cytokines and chemokines that can cross the blood-brain barrier leading to microglial activation and inflammation and ultimately neuronal cell death. Based on multiple avenues of evidence it appears likely that specific bacterial and particularly viral infections may increase vulnerability to PD. The implications of this for PD prevention requires attention and may be most relevant once preventive treatments for at-risk populations are developed.