A study and controls in Sweden showed that early and middle-aged infections treated in an outpatient or inpatient setting increased the risk of developing Alzheimer’s disease or later Parkinson’s disease.
Infections treated in hospital 5 or more years before diagnosis were associated with a 16% increased risk of Alzheimer’s disease (95% confidence interval 1.15–1.18, s<0.001) and a 4% higher risk of developing Parkinson's disease (95% CI 1.02–1.06, s<0.001), according to Jiangwei Sun, Ph.D., of the Karolinska Institutet in Stockholm, and colleagues.
Multiple infections treated in hospital before age 40 doubled the risk of a later Alzheimer’s diagnosis (OR 2.62, 95% CI 2.52–2.72, s<0.001) and an approximately 40% increased risk of a Parkinson's disease diagnosis (OR 1.41, 95% CI 1.29–1.53, s<0.001), the researchers reported in MEDICINE PLOS.
The associations were primarily due to Alzheimer’s disease and Parkinson’s disease diagnosed before age 60 (OR 1.93, 95% CI 1.89-1.98 for Alzheimer’s disease, s<0.001; OR 1.29, 95% CI 1.22-1.36 for Parkinson's disease, s<0.001). No associations were shown for people diagnosed at age 60 or older.
Similar risks were seen for bacterial, viral, and other infections and for various sites of infection, including infections of the gastrointestinal and urogenital tracts. No associations were observed between the diagnosis of infection and amyotrophic lateral sclerosis (ALS).
“These findings suggest that infectious events may be a trigger or amplifier of a pre-existing disease process, leading to the clinical onset of neurodegenerative disease at a relatively young age,” Son said. MedPage today. “However, given the observational nature of the study, these results do not formally establish a causal relationship.”
Potential viral and bacterial contributions to neurodegeneration have long been debated among researchers, notes Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, who was not involved in the study.
“However, no study to date has shown a strong causal relationship,” Griffin said. MedPage today.
“This paper indicates an association between hospitalized infections and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease,” he said. “One possible explanation for this is the inflammatory response to an infection – especially if it is serious enough that a visit to the hospital is necessary – that can contribute to or accelerate the neurodegenerative process by impairing the integrity of the blood-brain barrier.”
“More research is needed to better understand the mechanisms underlying this association,” Griffin noted.
The analysis included 291,941 cases of Alzheimer’s disease (median age at diagnosis was 76.2 and 46.6% of men), 103,919 cases of Parkinson’s disease (median age at diagnosis was 74.3 and 55.1% of men), and 10,161 cases of amyotrophic lateral sclerosis (Mean age at diagnosis was 69.3) and 56.8% of men).
The cases were of people newly diagnosed with Alzheimer’s disease, Parkinson’s disease, or ALS from 1970 through 2016 in the Swedish National Patient Registry. The registry included all inpatient care since 1987 and more than 80% of outpatient care since 2001. For each case, five controls matching for sex and year of birth were randomly selected from the general population.
The results were adjusted for gender, year of birth, region of residence, education, family history of neurodegenerative disease, and Charlson comorbidity index. Infection was excluded within 5 years prior to the diagnosis of Alzheimer’s disease, Parkinson’s disease, or ALS to reduce potential surveillance bias or reverse causation.
The researchers noted that excluding infections that occurred within 10 years before a diagnosis of Alzheimer’s disease or Parkinson’s disease confirmed the findings.
“The mechanisms underlying the association between infection and neurodegenerative diseases may not be specific to specific pathogens or affected organs but may occur at the systemic level,” Sun and colleagues write. The team added that the infection may lead to the clinical emergence of Alzheimer’s disease or Parkinson’s disease at a relatively young age among people who are predisposed to the disease.
The researchers acknowledged that limitations included potential misclassification of hospital-treated infections and neurodegenerative diseases due to incomplete coverage of national patient registry data. Residual confusion may also have an effect on the results.
This study was supported by the Swedish Research Council, the Joint Program on Neurodegenerative Diseases, and the China Scholarship Council.
A researcher coordinated a study on behalf of the Swedish IBD Quality Registry that received funding from the Janssen Corporation. No other competing interests have been declared.