Parkinson’s Risk Tied to Early, Midlife Hospital-treated Infections

A new study suggests that infections that require treatment in a specialty hospital are associated with an increased risk of developing Parkinson’s disease later in life. An increased risk has also been observed for Alzheimer’s disease, but not for amyotrophic lateral sclerosis (ALS).

“Hospital-treated infections, particularly in early and middle-aged individuals, have been associated with an increased risk of Alzheimer’s disease (AD) and Parkinson’s disease (PD), mainly in cases diagnosed before the age of 60,” said Jiangwei Sun, PhD, the first author of the study, said in a press release.

The study “Hospital-acquired infections in early and middle-aged people and risk for Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis: A nationwide nested case-control study in Swedenappeared in PLOS medicine.

Previous experimental studies in animals suggest that infections play a role in the development of neurodegenerative diseases. However, evidence in humans is limited.

Some studies have looked at the possible contribution of pathogens such as influenza, Helicobacter pylori, and hepatitis C virus to Parkinson’s disease, but the results were inconclusive.

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A research team from Karolinska Institute, Sweden, analyzed data from people diagnosed with Parkinson’s, Alzheimer’s and ALS in Sweden between 1970 and 2016, identified from the national patient registry. For each case, five people of matching sex and age were randomly selected from the general population to serve as controls.

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The analysis included 103,919 Parkinson’s cases (mean age at diagnosis 74.3; 55.1% were males), 291,941 Alzheimer’s cases (mean age at diagnosis 76.2; 46.6% were males), and 10,161 ALS cases ( mean age at diagnosis 69.3; 56.8% were male).

Infections within five years prior to diagnosis of neurodegenerative disease were excluded because confounding factors might be present. Results were also adjusted based on other potential confounders, namely the patient’s gender, year of birth, place of residence, level of education, family history of neurodegenerative diseases, and an index of comorbidities.

Hospital-treated infection was found to be associated with a 4% greater risk of developing Parkinson’s disease five years or more before diagnosis of neurodegenerative disease. The risk was independent of the type of infection – bacterial, viral or other. In addition, the risk of infections occurring in different parts of the body, namely the gastrointestinal and genitourinary systems, was identical.

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Patients with multiple infections who had to be hospitalized before the age of 40 had a more than 40% higher risk of developing Parkinson’s disease.

An increased risk of Alzheimer’s was also found. It was 16% higher in patients with a hospital-treated infection five years or more before diagnosis and more than doubled in patients with multiple infections before age 40. No association with ALS has been established.

The association between infections and Parkinson’s disease emerged when patients were diagnosed before age 60, but not when diagnosed at age 60 or older. The same has been observed for Alzheimer’s disease.

The “results that hospital-treated infections were more strongly associated with risk of AD and PD before age 60 than later, and that individuals with recurrent infections in early and middle-aged life were at greatest risk for AD and PD are recent and potentially important,” the researchers wrote. “We hypothesize that infectious events may be a trigger or an amplification of a pre-existing disease process, leading to clinical onset of a neurodegenerative disease at a relatively early age.”

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The mechanisms linking infection to neurodegenerative diseases “do not appear to be specific to particular pathogens or affected organs, but may occur at the systemic level,” they added.

These mechanisms could be related to changes in the structure and aggregation of proteins (alpha-synuclein in Parkinson’s disease); Inflammation at sites of infection that releases inflammatory molecules that can enter the central nervous system (CNS) and cause inflammation in the nervous system; and infiltration of cells of the immune system into the CNS.

However, “due to the observational nature of the study, these results do not formally prove a causal relationship,” the scientists wrote, adding that further research “could validate these results, elucidate underlying mechanisms, and determine whether better control of hospital-treated infections could do so.” Prevent or delay the onset of neurodegenerative diseases, particularly those that begin relatively early in life.”

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