Common Bacterial Infections and Risk of Dementia or Cognitive Decline: A Systematic Review

Abstract

Background: Bacterial infections may be associated with dementia, but the temporality of any relationship remains unclear. Objectives: To summarize existing literature on the association between common bacterial infections and the risk of dementia and cognitive decline in longitudinal studies. Methods: We performed a comprehensive search of 10 databases of published and grey literature from inception to 18 March 2019 using search terms for common bacterial infections, dementia, cognitive decline, and longitudinal study designs. Two reviewers independently performed the study selection, data extraction, risk of bias and overall quality assessment. Data were summarized through a narrative synthesis as high heterogeneity precluded a meta-analysis. Results: We identified 3,488 studies. 9 met the eligibility criteria; 6 were conducted in the United States and 3 in Taiwan. 7 studies reported on dementia and 2 investigated cognitive decline. Multiple infections were assessed in two studies. All studies found sepsis (n = 6), pneumonia (n = 3), urinary tract infection (n = 1), and cellulitis (n = 1) increased dementia risk (HR 1.10; 95% CI 1.02-1.19) to (OR 2.60; 95% CI 1.84-3.66). The range of effect estimates was similar when limited to three studies with no domains at high risk of bias. However, the overall quality of evidence was rated very low. Studies on cognitive decline found no association with infection but had low power. Conclusion: Our review suggests common bacterial infections may be associated with an increased risk of subsequent dementia, after adjustment for multiple confounders, but further high-quality, large-scale longitudinal studies, across different healthcare settings, are recommended to further explore this association.

Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort

“…We used Wald tests to compute p values for differences between the dementia risk related to different infections. The proportional hazards assumption was examined using scaled Schoenfeld residuals (appendix pp 11,[13][14][15].…”

“…[2][3][4] Genes that predispose individuals to dementia are involved in inflammatory pathways; 2 systemic inflammation has been associated with acce lerated cognitive decline and dementia in prospective studies; [5][6][7] and associations between infection and dementia have been found in several independent cohorts. [8][9][10][11][12][13] Alternative explanations of these findings exist. The germ hypothesis, supported by animal models of herpes simplex virus type 1, 14,15 proposes that specific microbes can cause Alzheimer's disease; 3,4,16 however, there is little, inconsistent evidence for herpes viruses in the human brain.…”

“… 2 , 3 , 4 Genes that predispose individuals to dementia are involved in inflammatory pathways; 2 systemic inflammation has been associated with accelerated cognitive decline and dementia in prospective studies; 5 , 6 , 7 and associations between infection and dementia have been found in several independent cohorts. 8 , 9 , 10 , 11 , 12 , 13 …”

Assessment of common infections and incident dementia using UK primary and secondary care data: a historical cohort study

“…Common infections are an established risk factor for acute cognitive impairment in older adults (≥65 years) and increasing evidence from longitudinal studies suggests that common infections are associated with an increased risk of dementia. 3 However, previous studies have mainly focused on sepsis or pneumonia hospitalisations rather than on a wide range of infections in different clinical settings, 4 , 5 , 6 , 7 , 8 and have had short follow-up periods (3–5 years), 4 , 7 relatively small sample sizes (between 3069 and 5955 participants or cases), 5 , 6 , 7 or inadequate adjustment for confounding. 6 , 7 , 8 Large-scale longitudinal studies published since 2016 have overcome some of these limitations; however, these studies have only been done in veterans, 9 stroke survivors, 10 or patients in intensive care unit, 11 restricting the generalisability of their findings.…”

Insights and Perspectives Regarding Nanostructured Fluorescent Materials toward Tackling COVID-19 and Future Pandemics

“…Bacterial infection has been the most common reason of many fatal diseases, such as pneumonia, dermatosis, sepsis, etc. 17 Similarly, viral infections cause severe diseases such as smallpox, acquired immunodeficiency syndrome (AIDS), chickenpox, influenza, and Ebola. Numerous techniques have been developed for pathogen detection, identification, and treatment such as plating, culturing, enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), microarrays analysis, biosensors, etc.…”