Flu May Be Linked to Increased Risk of Parkinson Disease, Danish Study Finds

Researchers recently published findings that add to previous evidence that having the flu may lead to a higher risk for Parkinson disease (PD) more than 10 years later.

Whether influenza is linked with PD has been the topic of debate dating back to the the flu epidemic of 1918, the researchers noted; between 1916 and 1930, there was an increase in “postencephalitic parkinsonism.” In addition, before the appearance of clinical PD symptoms, the prodromal phase is now thought to last 10 to 20 years. While no cause (or cure) for PD is known, some genes as well as lifestyle and environmental factors are believed to have a role.

The long prodromal phase, along with the question of what, if any, role previous infection plays in the development of PD, led to the researchers' hypothesis; their work was published in JAMA Neurology.

One of the benefits of universal health care is that researchers have access to population-wide data; in Denmark, citizens are assigned a unique personal identification number, “which permits unambiguous individual-level linkage among all Danish registries,” the researchers noted. Researchers have access to the Danish National Patient Registry, which has recorded all diagnoses and procedures from inpatient hospitalizations since 1977 and all hospital-based outpatient clinic visits since 1995.

The current study identified all patients diagnosed with PD from January 1, 2000, through December 31, 2016. Patients with early-onset PD were excluded, as were those with drug-induced secondary parkinsonism.

Infection was defined as any inpatient or outpatient contact linked with a primary or secondary discharge diagnosis of infection. Researchers used 2 different exposure definitions—a diagnosis code at any time during a given calendar year, and in a sensitivity analysis, documented flu diagnoses during seasonal peak activity—in order to capture the positive predictive value of an influenza diagnosis.

After exclusions, there were 10,271 individuals with PD; 3971 (38.7%) were female and 8867 (86.3%) were older than 60 years at diagnosis; the mean (SD) age was 71.4 (10.6) years. These patients were matched by age, sex, and certain comorbid conditions to 51,355 controls.

Results showed that the risk of developing PD more than 10 years after infection were raised by more than 70%; for PD occurring more than 15 years later, the risk was approximately 90% higher.

At 10 years, the odds ratio (OR) for PD when having flu at any time during the year was 1.73 (95% CI, 1.11-2.71) and at more than 15 years, 1.91 (95% CI, 1.14-3.19).

However, when limiting flu to peak seasons, patients were more than 50% likely to have PD later on (95% CI, 0.80-2.89)

There was no evidence of a link with any type of infection more than 10 years before PD (OR, 1.04; 95% CI, 0.98-1.10), except for urinary tract infections, which had a slightly higher risk more than 10 years later (OR, 1.19; 95% CI, 1.01-1.40).

The study had several limitations. Family history of PD and the role of genetics could not be known from the data. Second, it is possible that some flu cases were misclassified, since they were not confirmed by a laboratory. In addition, residual confounding from smoking could be a possibility, but would not have changed the results. Smoking is linked with increased vulnerability to both infection and influenza, but appears to be protective against PD.

Reference

Cocoros NM, Svensson E, Szépligeti SK, et al. Long-term risk of Parkinson disease following influenza and other infections. JAMA Neurol. 2021;78(12):1461-1470. doi:10.1001/jamaneurol.2021.3895