Raised Disease Risk Tied to Early, Midlife Hospital-treated Infections
Patients younger than 40 with multiple infections had more than 40% higher risk
A new study suggests that infections requiring specialty hospital care are associated with an increased risk of developing Parkinson’s disease later in life. An increased risk also was observed for Alzheimer’s disease, but not for amyotrophic lateral sclerosis (ALS).
“Hospital-treated infections, especially in early- and mid-life, were associated with an increased risk of Alzheimer’s disease (AD) and Parkinson’s disease (PD), primarily among cases diagnosed before 60 years,” Jiangwei Sun, PhD, the first author of the study, said in a news release.
The study “Hospital-treated infections in early- and midlife and risk of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis: A nationwide nested case-control study in Sweden” was published in PLOS Medicine.
Previous experimental studies in animals suggest infection plays a role in developing neurodegenerative diseases. Evidence in humans is limited, however.
Some studies addressed the possible contribution of pathogens such as influenza, Helicobacter pylori, and hepatitis C virus to Parkinson’s disease, but the results were inconclusive.
A research team from the Karolinska Institute, Sweden, analyzed data from people diagnosed with Parkinson’s disease, Alzheimer’s disease, and ALS from 1970-2016 in Sweden who were identified from the National Patient Register. For each case, five people matching in sex and age were randomly selected from the general population to serve as controls.
The analysis included 103,919 Parkinson’s disease cases (median age at diagnosis, 74.3; 55.1% were men), 291,941 Alzheimer’s disease cases (median age at diagnosis, 76.2; 46.6% were men), and 10,161 ALS cases (median age at diagnosis, 69.3; 56.8% were men).
Infections within five years before a neurodegenerative disease diagnosis were excluded because there could be confounding factors. The results were also adjusted based on other potential confounders, namely the patient’s sex, year of birth, area of residence, educational level, family history of neurodegenerative disease, and an index of comorbidities.
A hospital-treated infection five years or more before a neurodegenerative disease diagnosis was found to be associated with a 4% higher risk of developing Parkinson’s. The risk was independent of the type of infection — bacterial, viral, or other. Also, the risk was identical for infections occurring at different parts of the body, namely the gastrointestinal and genitourinary systems.
In patients with multiple infections requiring hospital care before age 40, the risk of developing Parkinson’s disease was more than 40% higher.
An increased risk for Alzheimer’s was also established. It was 16% higher in patients with one hospital-treated infection five years or more before the disease diagnosis and more than double in patients with multiple infections before age 40. No association was established for ALS.
The association between infections and Parkinson’s disease occurred when patients were diagnosed before age 60, but not when they were diagnosed at 60 or older. The same was observed for Alzheimer’s disease.
The “findings that hospital-treated infections were more strongly associated with risk of AD and PD before 60 years, compared to later, and that individuals with repeated infections in early- and mid-life had the greatest risk increment of AD and PD, are new and potentially important,” the researchers wrote. “We hypothesize that infectious events may be a trigger or amplifier of a preexisting disease process, leading to clinical onset of neurodegenerative disease at a relatively early age.”
The mechanisms linking infections to neurodegenerative diseases appear “not to be specific to certain pathogens or affected organs, but possibly occur at the systemic level,” they added.
These mechanisms might relate to alterations in the structure and aggregation of proteins (alpha-synuclein in Parkinson’s); inflammation at infection sites that release inflammatory molecules that can enter the central nervous system (CNS) and induce inflammation in the nervous system; and infiltration of cells from the immune system into the CNS.
Yet, “due to the observational nature of the study, these results do not formally prove a causal link,” the scientists wrote, adding further research could “validate these findings, to elucidate underlying mechanisms, and to determine whether better control of hospital-treated infections could prevent or delay onset of neurodegenerative diseases, especially the ones with an onset relatively early in life.”
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