Infectious disease burden and cognitive function in young to middle-aged adults

Highlights

• Cognition in young and middle-aged adults may be affected by infectious disease.

• Past infectious diseases may interact with one another to affect cognition.

• Age, ethnicity, education, SES may moderate impact of infectious disease on cognition.

Abstract

Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20–59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults.

Introduction

Exposure to infectious disease has been associated with cognitive function in humans. In one study of older adults, cognitive decline was associated with cytomegalovirus (CMV) but not herpes simplex virus type 1 (HSV-1) (Aiello et al., 2006), and in another study, Tarter et al. (2014) found that both HSV-1 and CMV were associated with cognition in children, younger adults, and older adults (Tarter et al., 2014). Adults over age 60 with previous hepatitis A virus (HAV) infection but intact liver function and no other hepatitis viruses had slower psychomotor speed than controls (Hsieh et al., 2009). Similarly, some patients with chronic hepatitis C virus (HCV) have cognitive deficits even in the absence of severe hepatic fibrosis (Perry et al., 2008). In addition to associations between viral infection and cognitive function, parasitic infections have also been related to cognitive impairment. Toxoplasma gondii (T. gondii) has been associated with cognitive impairment in adults (Flegr et al., 2003, Gajewski et al., 2014, Gale et al., 2015a, Mendy et al., 2015, Pearce et al., 2014), and Toxocara species have been associated with cognitive impairment in children (Walsh and Haseeb, 2012) and in adults (Erickson et al., 2015).

Many of the infectious diseases associated with cognition in humans have widespread distributions. The seroprevalence of CMV in the United States is approximately 59%, although the seroprevalence varies significantly with age and sociodemographic variables (Cannon et al., 2010, Staras et al., 2006). For example, the seroprevalence of CMV in children ages 6–11 years is approximately 36.3% increasing to 41.7% for ages 12–19 years (Staras et al., 2006). The overall seroprevalence of HSV-1 and HSV-2 have been reported as approximately 53.9% and 15.7%, respectively (Bradley et al., 2014). The prevalences of HSV-1 and HSV-2 are typically lower in children compared to adults with the prevalence of HSV-1 in adolescents 12–19 years of age being approximately 44% (Schillinger et al., 2004). The worldwide immunoglobulin G antibody (IgG) seroprevalence of T. gondii is approximately 30%, and its overall seroprevalence in the United States is estimated at 22% (Jones et al., 2001), with a prevalence of approximately 9% in adolescents and 8% in children (Jones et al., 2003). Similarly, the overall seroprevalence of Toxocara species in the United States is approximately 14% (Lee et al., 2014a), and the prevalence in children is slightly lower at approximately 12% (Nelson et al., 1996, Walsh and Haseeb, 2012). The seroprevalence of HAV in the United States prior to availability of the vaccine has been reported to have been approximately 30% overall and 8% in children (Klevens et al., 2011). The prevalence of HCV is approximately 1% in the United States (Denniston et al., 2014) and approximately 0.3% in children (Alter et al., 1999). Finally, the prevalence of hepatitis B (HCB) is approximately 5% overall and 1.2% in children (Wasley et al., 2010). As can be seen, these infectious diseases vary by age with a higher prevalence associated with increasing age. With these individual widespread distributions, some people may possess antibodies for multiple infectious diseases, any one of which could influence cognition, but not necessarily to the same degree. Further, prior studies have shown that many of these infectious diseases may not only affect cognition but multiple infections may interact to affect cognitive function (Gale et al., 2015b).

To more fully investigate the cumulative effect of more than one infectious disease, Katan et al. (2013) evaluated the association between several viral and bacterial infections and cognition in a sample of older adults (mean age = 69). They calculated the effect of these infections on cognition by weighting the ability of each infection to predict cognitive function and then summing these weights into an overall index of infectious disease burden. They included CMV, HSV-1, HSV-2, Helicobacter pylori (H. pylori), and Chlamydia pneumoniae (C. pneumoniae) and found that a greater infectious-disease index was associated with poorer cognitive function.

Based on the associations between viral, bacterial, and parasitic diseases and cognitive function in humans and the relationship between an index of total infectious-disease burden and human cognitive function, we hypothesized that the association between an infectious-disease burden taking into account total exposure to the viruses herpes types 1 and 2, hepatitis A, B, and C, and CMV, the protozoan T. gondii, and the nematodes Toxocara cati and Toxocara canis would be associated with neurocognitive function in a sample of young- and middle-aged adults. We chose these particular pathogens because they either had been previously associated with human cognitive impairment or were related to infectious diseases previously associated with cognitive impairment. We chose covariates a priori to reflect factors that we have found in prior work to affect the association between cognition and certain pathogens (Erickson et al., 2015, Gale et al., 2015a, Gale et al., 2015b). Specifically, we controlled for socioeconomic status, educational attainment, and ethnicity and investigated interactions between these covariates and the pathogens.