White matter hyperintensities in patients with Parkinson's disease: A systematic review and meta-analysis

Butt, Asif; Kamtchum‐Tatuene, Joseph; Khan, Khurshid; Shuaib, Ashfaq; Jickling, Glen C.; Smith, Eric E.; Camicioli, Richard

doi:10.1016/j.jns.2021.117481

Cited by 24 publications

(26 citation statements)

References 71 publications

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“…It is the first cohort study we are aware of to find an association between WMD and a subsequent diagnosis of PD. We note also that prior case–control and pathological studies have found an inconsistent association between cerebrovascular disease and PD 12 . However, these cross‐sectional studies are prone to issues of reverse causation which are avoided in cohort studies, since cohort studies can select patients free of PD at baseline and follow them over time.…”

Section: Discussionmentioning

confidence: 96%

“…Previous studies have examined whether WMD in patients with existing PD correlates with severity or progression 6–11 . One systematic review and meta‐analysis of case–control studies suggested that white matter hyperintensities were not more prevalent or severe in patients with PD 12 . However, case control studies are fundamentally limited because associations may be obscured through reverse causation (i.e., PD and its treatment may influence CCD).…”

Section: Introductionmentioning

confidence: 99%

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Development of Parkinson Disease and Its Relationship with Incidentally Discovered White Matter Disease and Covert Brain Infarction in a Real‐World Cohort

Kent

Leung

Puttock

et al. 2022

Annals of Neurology

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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.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Development of Parkinson Disease and Its Relationship with Incidentally Discovered White Matter Disease and Covert Brain Infarction in a Real‐World Cohort

Kent

Leung

Puttock

et al. 2022

Annals of Neurology

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“…[27][28][29] We note that prior case-control and pathological studies have found an inconsistent association between cerebrovascular disease and PD. 12 These cross-sectional studies are more prone to issues of reverse causation than cohort studies, since cohort studies can select patients free of PD at baseline and follow them over time. Prior investigators have speculated that PD may reduce the risk of cerebrovascular disease, either through lower levels of dopamine in the brain or as a result of the blood pressure lowering effects of levodopa, which might obscure the relationship between prior cerebrovascular disease and PD.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9][10][11] One systematic review and meta-analysis of case-control studies suggested that white matter hyperintensities were not more prevalent or severe in patients with PD. 12 However, case control studies are fundamentally limited because associations may be obscured through reverse causation (i.e., PD and its treatment may influence CCD). In part because the incidence of PD is relatively low, and because CCD is not identifiable using databases from routine care, no study has yet examined the association of CCD with future incidence of PD.…”

Section: Introductionmentioning

confidence: 99%

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

Kent

Leung

Puttock

et al. 2022

Preprint

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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.

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“…In fact the authors have previously noted reduced prevalence of both vascular risk factors and SVD in autopsy-proven PD compared with community controls [27]. A recent large meta-analysis failed to demonstrate an increase in WMHs in PD compared to age-matched controls [28]. Conversely, post-mortem analysis of 617 patients has shown an increased frequency of all markers of SVD in PD compared to controls [18].…”

Section: Comorbid Cerebrovascular Disease and Pdmentioning

confidence: 99%

Parkinsonism and cerebrovascular disease

Narasimhan

Schwartz

Halliday

2022

Journal of the Neurological Sciences

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White matter hyperintensities in patients with Parkinson's disease: A systematic review and meta-analysis

Cited by 24 publications

References 71 publications

Development of Parkinson Disease and Its Relationship with Incidentally Discovered White Matter Disease and Covert Brain Infarction in a Real‐World Cohort

Development of Parkinson Disease and Its Relationship with Incidentally Discovered White Matter Disease and Covert Brain Infarction in a Real‐World Cohort

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

Parkinsonism and cerebrovascular disease

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