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Hospital-treated infections, especially during early and mid-life, may increase the risk for neurodegenerative disease, according to research. ALTO IMAGES/Stocksy
  • Researchers investigated the link between hospital-treated infections and neurodegenerative disease.
  • They found that hospital-treated infections, particularly during early and mid-life, increased the subsequent risk of developing Alzheimer’s disease and Parkinson’s disease later in life.
  • They noted that their study did not examine a causal relationship and that further research is thus required.

Neurodegenerative conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) are characterized by a progressive loss of neurons in the nervous system.

Multiple factors, including genetics and lifestyle, may contribute to a person’s neurodegenerative risk.

Some studies indicate that bacterial and viral infections also increase neurodegenerative risk. Such research, however, has largely produced inconclusive results due to study design limitations.

A better understanding of the link between infectious disease and neurodegeneration could help researchers develop therapeutic strategies for neurodegenerative conditions.

Recently, researchers analyzed Swedish health records to examine the link between hospital-treated infections and the risk of AD, PD, and ALS.

They found that hospital-treated infections, especially in early and mid-life, were linked to an increased risk of AD and PD, but not ALS.

The study was recently published in PLOS Medicine.

For the studies, the researchers examined healthcare records from 12,275,551 individuals from several national registers in Sweden. They followed them between 1970 and 2016 and recorded diagnoses of neurodegenerative diseases, emigration, and death.

Infections were recorded according to type- bacterial, viral, or other, and site- including the central nervous system (CNS), gastrointestinal tract, respiratory, or skin infection. Data also included age of infection and frequency.

The researchers excluded patients who had an infection within 5 years of neurodegenerative diagnosis to avoid surveillance bias and reverse causation.

Altogether, 291,941 people in the analysis developed Alzheimer’s, 103,919 had Parkinson’s, and 10,161 had ALS.

After analyzing the data, the researchers found that a hospital-treated infection 5 or more years prior to diagnosis was linked to a 16% higher risk of AD and a 4% higher risk of PD.

Similar risks were seen for bacterial, viral, and other infections and for different infection sites.

The link was primarily observed in those diagnosed with AD and PD before age 60, as opposed to those diagnosed later.

The biggest risk was observed among those with hospital-treated infections earlier in life; multiple infections before age 40 were linked to an almost double risk of AD and a 40% higher risk for PD.

The researchers noted, however, that there was no link between hospital-treated infection and ALS, and that their findings remained after controlling for factors including sex, family history of neurodegenerative disease, and education level.

While the study did not examine casualty, the researchers wrote that similar results for different infection types and sites might suggest the underlying mechanisms are linked to systematic inflammation instead of a specific pathogen response.

“Infectious events may [also] be a trigger or amplifier of a pre-existing disease process, leading to clinical onset of neurodegenerative disease at a relatively early age among individuals with disease predisposition,” Jiangwei Sun, Ph.D., a postdoctoral researcher in the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet in Sweden, one of the study’s authors, told MNT.

Prof Andrew Doig, Ph.D., of the Division of Neuroscience and Experimental Psychology at the University of Manchester, not involved in the study, told MNT: “[Furthermore], pathogens might produce compounds that promote the aggregation of amyloid-β or α-synuclein, which would lead to Alzheimer’s or Parkinson’s, respectively.”

When asked why a link between hospital-treated infections and neurodegenerative conditions was found in those ages 60 and under, but not older, Dr. Timo E. Strandberg, Ph.D., internal medicine doctor and professor of geriatrics at Helsinki University Hospital, Finland, not involved in the study, told MNT:

“[In a study my team and I conducted in 2003, looking at our geriatric cohort], there indeed was a significant relationship between viral burden and cognitive decline in 75+ people. However, in this age group, cognitive decline and dementia are usually multifactorial- genetic, neurodegenerative, vascular- which may be why the relationship was not observed in older people in the present study.”

– Dr. Timo E. Strandberg, Ph.D.

The researchers concluded that hospital-treated infections are linked to an increased risk of AD and PD diagnosis before age 60, although underlying mechanisms remain unknown.

When asked about the study’s limitations, Dr. Sun noted that they did not have complete information on all risk or protective factors for neurodegenerative conditions, including lifestyle factors, medical factors such as trauma or vascular-related brain damage, and genetic factors.

Charlotte Warren-Gash, Ph.D., an associate professor at the Faculty of Epidemiology and Population Health at the London School of Hygiene and Tropical Medicine, not involved in the study, also told MNT:

“The study covered a long period of time, from 1970 [to] 2016, during which diagnostic criteria and clinical practices have undergone major changes. How applicable results are to patients with infections today remains unclear.”

Dr. Doig added: “The people studied were all Swedish with both parents also born in Sweden, so the results may not generalize outside this group.”

Dr. Strandberg noted that a key message should be that “infections should be carefully treated — as they should anyway — with a low threshold for cognitive testing as needed.”

He added that further studies could examine whether antimicrobial treatments for recurrent infections such as herpes could help treat established cognitive disorders.

Dr. Warren-Gash agreed that more research is called for.

“Further studies using novel designs to account for limitations such as confounding and reverse causation are needed. While preventing and treating infections leads to health benefits in general, further research is needed on whether these interventions could specifically affect neurodegenerative disease risk.”

Charlotte Warren-Gash, Ph.D., associate professor at the London School of Hygiene and Tropical Medicine