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Long-term Risk of Parkinson Disease Following Influenza and Other Infections

Educational Objective
To examine whether prior influenza and other infections are associated with Parkinson disease.
1 Credit CME
Key Points

Question  Is influenza or other infection associated with Parkinson disease?

Findings  In this case-control study of all Danish citizens with Parkinson disease between 2000 and 2016, unlike most other infections, influenza was associated with Parkinson disease more than 10 years after infection.

Meaning  Influenza infection may increase the long-term risk of developing Parkinson disease.

Abstract

Importance  Influenza has been associated with the risk of developing Parkinson disease, but the association is controversial.

Objective  To examine whether prior influenza and other infections are associated with Parkinson disease more than 10 years after infection.

Design, Setting, and Participants  This case-control study used data from 1977 to 2016 from the Danish National Patient Registry. All individuals with Parkinson disease, excluding those with drug-induced parkinsonism, were included and matched to 5 population controls on sex, age, and date of Parkinson diagnosis. Data were analyzed from December 2019 to September 2021.

Exposures  Infections were ascertained between 1977 and 2016 and categorized by time from infection to Parkinson disease diagnosis. To increase specificity of influenza diagnoses, influenza exposure was restricted to months of peak influenza activity.

Main Outcomes and Measures  Parkinson disease diagnoses were identified between January 1, 2000, and December 31, 2016. Crude and adjusted odds ratios (ORs) and 95% CIs were calculated by conditional logistic regression overall and stratified by time between infection and Parkinson disease (5 years or less, more than 5 to 10 years, more than 10 years).

Results  Of 61 626 included individuals, 23 826 (38.7%) were female, and 53 202 (86.3%) were older than 60 years. A total of 10 271 individuals with Parkinson disease and 51 355 controls were identified. Influenza diagnosed at any time during a calendar year was associated with Parkinson disease more than 10 years later (OR, 1.73; 95% CI, 1.11-2.71). When influenza exposure was restricted to months of highest influenza activity, an elevated OR with a wider confidence interval was found (OR, 1.52; 95% CI, 0.80-2.89). There was no evidence of an association with any type of infection more than 10 years prior to Parkinson disease (OR, 1.04; 95% CI, 0.98-1.10). Several specific infections yielded increased odds of Parkinson disease within 5 years of infection, but results were null when exposure occurred more than 10 years prior.

Conclusions and Relevance  In this case-control study, influenza was associated with diagnoses of Parkinson disease more than 10 years after infection. These observational data suggest a link between influenza and Parkinson disease but do not demonstrate causality. While other infections were associated with Parkinson disease diagnoses soon after infection, null associations after more than 10 years suggest these shorter-term associations are not causal.

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Article Information

Accepted for Publication: September 7, 2021.

Published Online: October 25, 2021. doi:10.1001/jamaneurol.2021.3895

Corresponding Author: Noelle M. Cocoros, DSc, Department of Population Medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute, 401 Park Dr, Ste 401E, Boston, MA 02215 (noelle_cocoros@harvardpilgrim.org).

Author Contributions: Ms Szépligeti and Mr Szentkúti had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Cocoros, Svensson, Szentkúti, Borghammer, Sørensen, Henderson.

Acquisition, analysis, or interpretation of data: Cocoros, Svensson, Szépligeti, Vestergaard, Szentkúti, Thomsen, Sørensen.

Drafting of the manuscript: Cocoros, Svensson, Szentkúti, Borghammer.

Critical revision of the manuscript for important intellectual content: Cocoros, Szépligeti, Vestergaard, Szentkúti, Thomsen, Borghammer, Sørensen, Henderson.

Statistical analysis: Cocoros, Szépligeti, Szentkúti, Sørensen.

Obtained funding: Svensson, Sørensen.

Administrative, technical, or material support: Vestergaard, Sørensen.

Study supervision: Vestergaard, Borghammer, Sørensen.

Conflict of Interest Disclosures: Dr Svensson has received funding from the Augustinus Foundation. Dr Vestergaard has received grants from Lundbeck Foundation and Augustinus Foundation. Dr Henderson has received grants from the National Institutes of Health and personal fees from the National Institutes of Health, Canadian Consortium on Neurodegeneration in Aging, and Aarhus University. No other disclosures were reported.

Funding/Support: The project was supported by grants from the Lundbeck Foundation and the Augustinus Foundation. Dr Henderson was supported by grant P30 AG066515 from the National Institutes of Health.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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