Repeated infections associated with an increased risk of some neurodegenerative diseases

Summary: Infections in early and midlife that require hospital care are associated with an increased risk of developing Alzheimer’s and Parkinson’s later in life, a new study reports.

Source: RAIN

Infections treated with specialized hospital care in early and midlife are associated with an increased later risk of Alzheimer’s (AD) and Parkinson’s (PD), but not sclerosis, according to a new study published on September 15. amyotrophic lateral sclerosis (ALS).th in the open access journal PLOS Medicine by Jiangwei Sun of the Karolinska Institute, Sweden, and colleagues.

Experimental animal studies have suggested that infection plays a role in the development of some neurodegenerative diseases, but supporting evidence in humans is limited.

In the new study, the researchers used data on people diagnosed with AD, PD or ALS between 1970 and 2016 in Sweden, as well as five case-matched controls, all identified in the Swedish national patient registry. The analysis included 291,941 cases of AD, 103,919 cases of PD, and 10,161 cases of ALS.

Researchers evaluate hospital-treated infection and risk of neurodegenerative diseases. Credit: Jiangwei Sun

An infection treated in hospital 5 or more years before diagnosis was associated with a 16% higher risk of AD (95% CI: 1.15–1.18, P < 0.001) and a 4 Greater % of MP (95% CI: 1.02-1.06). , P < 0.001), with similar risks observed for bacterial, viral, and other infections and for different sites of infection. The highest risk of disease was seen in people with multiple infections treated in hospital before the age of 40, with more than twice the risk of AD (OR=2.62, 95% CI: 2.52-2.72 , P <0.001) and more than 40% increased risk of PE (OR=1.41, 95% CI: 1.29-1.53, 3 44 P <0.001). No association was observed for ALS, regardless of age at diagnosis. "These findings suggest that infectious events may be a trigger or amplifier of a pre-existing disease process, resulting in the clinical onset of neurodegenerative disease at a relatively early age," the authors say, noting that "a Because of the observational nature of the study, these results do not formally demonstrate a causal link." Sun adds: "Infections treated in hospital, particularly in early and middle life, were associated with an increased risk of Alzheimer's disease (AD) and Parkinson's disease (PD), mainly among AD cases and PD diagnosed before the age of 60". Funding: This study was supported by the Swedish Research Council (grants no: 2019-01088 (FF), 340-2013-5867 (FF) and 2017-02175 (KW)), the Joint Program on Neurodegenerative Diseases (JPND, grant number: 2021-00696 (FF)) and the Chinese Scholarship Council (JS). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

About this neurodegeneration research news

Author: Claire Turner
Source: RAIN
Contact: Claire Turner – PLOS
Image: Image is credited to Jiangwei Sun

Original Research: Open access
“Hospital-treated infections in early and midlife and risk of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis: a nationwide case-control study in Sweden” by Jiangwei Sun et al. PLOS Medicine


Summary

Hospital-treated infections in early and midlife and risk of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis: a randomized case-control study in Sweden

See also

This shows neurons from human and non-human primates

background

Experimental observations have suggested a role for infection in the etiology of neurodegenerative diseases. In human studies, however, it is difficult to disentangle whether infection is a risk factor or rather a comorbidity or secondary event of neurodegenerative disease. To this end, we examined the risk of the 3 most common neurodegenerative diseases in relation to previous episodes of hospital or outpatient infections.

Methods and findings

We conducted a randomized case-control study based on several national registries in Sweden. Cases were individuals newly diagnosed with Alzheimer’s disease (AD), Parkinson’s disease (PD), or amyotrophic lateral sclerosis (ALS) between 1970 and 2016 in Sweden, identified in the national patient registry. For each case, 5 controls individually matched to the case on sex and year of birth were randomly selected from the general population.

Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) with adjustment for potential confounders, including sex, year of birth, area of ​​residence, level of studies, family history of neurodegenerative disease and the Charlson comorbidity index. . Infections experienced in the 5 years before neurodegenerative disease diagnosis were excluded to reduce the influence of surveillance bias and reverse causation.

The analysis included 291,941 cases of AD (mean age at diagnosis: 76.2 years; men: 46.6%), 103,919 cases of PD (74.3; 55.1%) and 10,161 cases of ALS (69 .3; 56.8%). An infection treated in hospital 5 years or more previously was associated with an increased risk of AD (OR = 1.16, 95% CI 1.15 to 1.18, p <0.001) and PD (OR = 1.04, 95% CI 1.02 to 1.06, p <0.001). Similar results were observed for bacterial, viral and other infections and between different sites of infection, including gastrointestinal and genitourinary infections. Multiple infections before age 40 years conferred the highest risk of AD (OR = 2.62, 95% CI 2.52 to 2.72, p <0.001) and PD (OR = 1.41, 95% CI: 1.29 to 1.53, p <0.001). Associations were mainly due to AD and PD diagnosed before age 60 (OR = 1.93, 95% CI 1.89 to 1.98 for AD, p < 0.001; OR = 1.29, 95% CI 1.22 to 1.36 for PD, p < 0.001), while no association was found for those diagnosed aged 60 years or older (OR = 1.00, 95% CI 0.98 to 1.01 for AD, p = 0.508; OR = 1.01, 95% CI 0.99 to 1.03 for PD, p = 0.382). No association was observed for ALS (OR = 0.97, 95% CI 0.92 to 1.03, p = 0.384), regardless of age at diagnosis.

Exclusion of infections experienced in the 10 years prior to diagnosis of the neurodegenerative disease confirmed these findings. Study limitations include potential misclassification of hospital-treated infections and neurodegenerative diseases due to incomplete national patient registry coverage, as well as residual confounding by risk or protective factors not measured by to neurodegenerative diseases.

Conclusions

Infections treated in hospital, especially in early and middle life, were associated with an increased risk of AD and PD, mainly among cases of AD and PD diagnosed before age 60 years. 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 diseases at a relatively early age. However, due to the observational nature of the study, these results do not formally demonstrate a causal link.

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