Association of cytomegalovirus and Epstein-Barr virus with cognitive functioning and risk of dementia in the general population: 11-year follow-up study

Holm, Minna; Suvisaari, Jaana; Lindgren, Maija; Härkänen, Tommi; Dickerson, Faith; Yolken, Robert H.

doi:10.1016/j.bbi.2018.01.006

Cited by 37 publications

(26 citation statements)

References 27 publications

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“…Although the prevalence of CMV in Finland has decreased significantly during recent decades [54], the rate was as high as 84% in the population at our baseline in year 2000 [3]. The increased odds of multiple suicide attempts in persons belonging to the CMV seronegative minority is a new finding.…”

Section: Discussionmentioning

confidence: 71%

“…Toxoplasma gondii is an intracellular parasite, most commonly spread by food or water that is contaminated with oocysts shed by cats, or by eating meat-containing tissue cysts, whereas the herpes viruses spread mostly through bodily fluids, and are among the most common viruses in humans. In recent studies of the general population in Finland, the seropositivity prevalence in adults was 20% for T. gondii [1], 72% for HSV-1 [2], 84% for CMV, and 98% for EBV [3]. Associations between these infections and mental health have been repeatedly found.…”

Section: Introductionmentioning

confidence: 99%

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Exposure to common infections and risk of suicide and self-harm: a longitudinal general population study

Lindgren

Holm

Markkula

et al. 2020

Eur Arch Psychiatry Clin Neurosci

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Common infectious agents, such as Toxoplasma gondii (T. gondii) and several human herpes viruses, have been linked to increased risk of self-harm. The aim of this study was to investigate the associations between self-harm and seropositivity to T. gondii, Epstein-Barr virus (EBV), Herpes Simplex virus Type 1 (HSV-1), and Cytomegalovirus (CMV). IgM and IgG antibodies to these infections were measured in the Health 2000 project nationally representative of the whole Finnish adult population, and 6250 participants, age 30 and over, were followed for 15 years via registers. In addition, lifetime suicidal ideation and suicide attempts based on medical records and interview were assessed within a subsample of 694 participants screened to a substudy for possible psychotic symptoms or as controls. Among the 6250 participants, 14 individuals died of suicide and an additional 4 individuals had a diagnosis of intentional self-harm during follow-up. Serological evidence of lifetime or acute infections was not found to be associated with these suicidal outcomes. However, in the subsample, those seropositive for CMV had fewer suicide attempts compared to those seronegative, adjusting for gender, age, educational level, childhood family size, regional residence, CRP, and screen status (OR for multiple attempts = 0.40, 95% confidence interval 0.20-0.83, p = 0.014). To conclude, common infections were not associated with risk of death by suicide or with self-harm diagnoses at a 15-year follow-up in the general population sample. Our finding of an increased number of suicide attempts among persons seronegative for CMV calls for further research.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Exposure to common infections and risk of suicide and self-harm: a longitudinal general population study

Lindgren

Holm

Markkula

et al. 2020

Eur Arch Psychiatry Clin Neurosci

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“…Are T. gondii seropositive patients with schizophrenia a distinct subgroup of patients (even requiring a different treatment regime)? In addition, some studies provide an association between T. gondii seropositivity and human behavior or neurocognitive impairment (163–165) while other studies do not find such association (166–168).…”

Section: Reactivated Toxoplasmosis In the Cnsmentioning

confidence: 99%

Advances and Challenges in Understanding Cerebral Toxoplasmosis

2019

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Toxoplasma gondii is a widespread parasitic pathogen that infects over one third of the global human population. The parasite invades and chronically persists in the central nervous system (CNS) of the infected host. Parasite spread and persistence is intimately linked to an ensuing immune response, which does not only limit parasite-induced damage but also may facilitate dissemination and induce parasite-associated immunopathology. Here, we discuss various aspects of toxoplasmosis where knowledge is scarce or controversial and, the recent advances in the understanding of the delicate interplay of T. gondii with the immune system in experimental and clinical settings. This includes mechanisms for parasite passage from the circulation into the brain parenchyma across the blood-brain barrier during primary acute infection. Later, as chronic latent infection sets in with control of the parasite in the brain parenchyma, the roles of the inflammatory response and of immune cell responses in this phase of the disease are discussed. Additionally, the function of brain resident cell populations is delineated, i.e., how neurons, astrocytes and microglia serve both as target cells for the parasite but also actively contribute to the immune response. As the infection can reactivate in the CNS of immune-compromised individuals, we bring up the immunopathogenesis of reactivated toxoplasmosis, including the special case of congenital CNS manifestations. The relevance, advantages and limitations of rodent infection models for the understanding of human cerebral toxoplasmosis are discussed. Finally, this review pinpoints questions that may represent challenges to experimental and clinical science with respect to improved diagnostics, pharmacological treatments and immunotherapies.

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“…However, most studies on CMV and dementia are based on seroprevalence or the serostatus of latent CMV and were assessed using serum CMV immunoglobulin G (IgG). Although serum CMV IgG was suggested to play a role in neurodegeneration with cognitive impairment [7,9,10], a significant association between CMV serostatus indicating past infection without virus replication and dementia was not observed in a recent long-term follow-up study and meta-analysis [11,12].…”

Section: Introductionmentioning

confidence: 95%

Association between cytomegalovirus end-organ diseases and moderate-to-severe dementia: a population-based cohort study

et al. 2020

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Background: The association between cytomegalovirus (CMV) and dementia remains controversial. Previous studies have suggested that CMV serostatus, as assessed by serum immunoglobulin G, plays a role in neurodegeneration with cognitive impairment. We aimed to evaluate the association between CMV tissue-invasive end-organ diseases and moderate-to-severe dementia. Methods: The ICD 10th revision codes from the National Health Insurance Database covering the entire population of the Republic of Korea were used to classify patients into exposed (n = 687, age ≥ 40 years, with CMV disease) and unexposed (n = 3435, without CMV disease) groups, matched by age and sex at a 1:5 ratio of exposed: unexposed. All non-HIV-1-infected subjects selected during 2010-2014 with a washout period of the previous 4 years were followed up until December 2016 to identify newly diagnosed cases of moderate-to-severe dementia. Results: Multivariate regression model (M3) adjusted for age, sex, low income, body mass index, transplantation status, malignant neoplasms, end-stage renal disease on dialysis, type 2 diabetes mellitus, hypertension, and dyslipidaemia showed a significantly higher incidence of dementia (odds ratio: 1.9; 95% confidence interval: 1.2-2.8) in the exposed group than that in the unexposed group. The risk of vascular dementia (2.9, 1.1-7.5) was higher than that of Alzheimer's disease (1.6, 1.0-2.6) in the exposed group in M3. In M3, patients aged 40-59 years with CMV diseases had a significantly higher risk of all kinds of dementia than those aged 60-79 and ≥ 80 years (11.7, 2.5-49.4 vs. 1.8, 1.1-3.2 vs. 1.3, 0.5-2.8; P = 0.025). Conclusions: CMV diseases may be associated with the risk of moderate-to-severe dementia.

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Association of cytomegalovirus and Epstein-Barr virus with cognitive functioning and risk of dementia in the general population: 11-year follow-up study

Abstract: The results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level.

Cited by 37 publications

References 27 publications

Exposure to common infections and risk of suicide and self-harm: a longitudinal general population study

Exposure to common infections and risk of suicide and self-harm: a longitudinal general population study

Advances and Challenges in Understanding Cerebral Toxoplasmosis

Association between cytomegalovirus end-organ diseases and moderate-to-severe dementia: a population-based cohort study

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