Virus exposure and neurodegenerative disease risk across national biobanks

Levine, Kristin; Leonard, Hampton; Blauwendraat, Cornelis; Iwaki, Hirotaka; Johnson, Nicholas; Bandrés‐Ciga, Sara; Ferrucci, Luigi; Faghri, Faraz; Singleton, Andrew B.; Nalls, Mike A.

doi:10.1016/j.neuron.2022.12.029

Cited by 170 publications

(126 citation statements)

References 34 publications

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“…The brain is protected from most viral pathogens by the bloodbrain barrier, but neurotropic viruses can subvert these protective measures to infect cells of the nervous system. Interestingly, the majority of associations identified in the study by Levine et al 4 involved viruses that are considered to be neurotropic, including HSV, varicella zoster virus (VZV), some strains of influenza virus, and viruses that cause encephalitis or meningitis. The most common causes of viral encephalitis are HSV, VZV and West Nile virus, and although neurotropic viruses have long been recognized to cause post-infectious cognitive dysfunction, it is less clear whether these viruses cause classic neurodegenerative diseases.…”

Section: Competing Interestsmentioning

confidence: 99%

“…The table lists the viral infections that were found to be associated with an increased risk of neurodegenerative disease in the study by Levine et al 4 .…”

Section: Competing Interestsmentioning

confidence: 99%

“…In a recent study, Kristin Levine and colleagues mined medical record data and found that viral infections were associated with an increased risk of several neurodegenerative diseases 4 (Table 1). This study is the most expansive of its nature, evaluating various viral agents and several neurodegenerative diseases from two different datasets: a nationwide Finnish biobank including over 300,000 individuals and a second biobank from the UK with data from nearly 500,000 individuals.…”

mentioning

confidence: 99%

“…Influenza and pneumonia together showed significant associations with all the diseases examined except for MS. A previously reported association between Epstein-Barr virus (EBV) infection and MS 5 was replicated using the Finnish but not the UK dataset. This discrepancy might be attributable to differences between countries in how illnesses are reported in medical records 4 .…”

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confidence: 99%

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Viral pathogens increase risk of neurodegenerative disease

Blackhurst

Funk

2023

Nat Rev Neurol

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Section: Competing Interestsmentioning

confidence: 99%

“…The table lists the viral infections that were found to be associated with an increased risk of neurodegenerative disease in the study by Levine et al 4 .…”

Section: Competing Interestsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Viral pathogens increase risk of neurodegenerative disease

Blackhurst

Funk

2023

Nat Rev Neurol

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“…Whether such SARS‐CoV‐2‐induced brain anomalies could predispose to neurodegenerative diseases in the future remains an open question. This possibility has been suggested for other viruses [10].…”

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confidence: 73%

Long COVID: Does SARS‐CoV‐2 induce lingering brain lesions?

Hugon

2023

Euro J of Neurology

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Hundreds of millions of COVID cases have been reported so far and long‐term lingering clinical symptoms are frequent and are called long COVID. Neurological signs including cognitive complaints are often described in long Covid. In COVID patients, the Sars‐Cov‐2 virus can reach the brain and could be responsible for cerebral anomalies observed in long COVID. Long‐term careful clinical follow‐up of these patients is necessary to detect early signs of neurodegeneration.

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Hospital-Diagnosed Infections, Autoimmune Diseases, and Subsequent Dementia Incidence

Janbek,

Laursen,

Frimodt-Møller

et al. 2023

JAMA Netw Open

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ImportanceSystemic inflammation has been suggested to explain reported associations between infections and dementia. Associations between autoimmune diseases and dementia also suggest a role for peripheral systemic inflammation.ObjectiveTo investigate the associations of infections and autoimmune diseases with subsequent dementia incidence and to explore potential shared signals presented by the immune system in the 2 conditions.Design, Setting, and ParticipantsThis nationwide, population-based, registry-based cohort study was conducted between 1978 and 2018 (40-year study period). All Danish residents born 1928 to 1953, alive and in Denmark on January 1, 1978, and at age 65 years were included. Persons with prior registered dementia and those with HIV infections were excluded. Data were analyzed between May 2022 and January 2023.ExposuresHospital-diagnosed infections and autoimmune diseases.Main Outcomes and MeasuresAll-cause dementia, defined as the date of a first registered dementia diagnosis after age 65 years in the registries. Poisson regression with person-years at risk as an offset variable was used to analyze time to first dementia diagnosis.ResultsA total of 1 493 896 individuals (763 987 women [51%]) were followed for 14 093 303 person-years (677 147 [45%] with infections, 127 721 [9%] with autoimmune diseases, and 75 543 [5%] with dementia). Among individuals with infections, 343 504 (51%) were men, whereas among those with autoimmune diseases, 77 466 (61%) were women. The dementia incidence rate ratio (IRR) following any infection was 1.49 (95% CI, 1.47-1.52) and increased along with increasing numbers of infections in a dose-dependent manner. Dementia rates were increased for all infection sites in the short term, but not always in the long term. The dementia IRR following any autoimmune disease was 1.04 (95% CI, 1.01-1.06), but no dose-dependent increase was observed, and only a few autoimmune conditions showed increased IRRs for dementia.Conclusions and RelevanceThese findings may point toward a role for infection-specific processes in the development of dementia, rather than general systemic inflammation, as previously hypothesized. Assessing these 2 conditions in a single setting may allow for additional insights into their roles in dementia and for hypotheses on possible underlying mechanisms.

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Virus exposure and neurodegenerative disease risk across national biobanks

Cited by 170 publications

References 34 publications

Viral pathogens increase risk of neurodegenerative disease

Viral pathogens increase risk of neurodegenerative disease

Long COVID: Does SARS‐CoV‐2 induce lingering brain lesions?

Hospital-Diagnosed Infections, Autoimmune Diseases, and Subsequent Dementia Incidence

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