Cognitive ability in early adulthood is associated with systemic inflammation in middle age: The Vietnam experience study

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Abstract

We examined the prospective association between cognitive ability in early adulthood and erythrocyte sedimentation rate, a marker of inflammation, in middle age. Participants were 4256 male Vietnam era US veterans. Data on cognitive ability, assessed by the Army General Technical Test, ethnicity, and place of service were extracted from enlistment files. Smoking behaviour, alcohol consumption, basic socio-demographics, and whether participants suffered from a physician diagnosed chronic disease were determined by telephone interview in middle-age in 1985. Erythrocyte sedimentation rate, cholesterol, blood pressure, height, and weight were measured at a 3-day medical examination in 1986. In linear regression models that adjusted for age and then additionally for circumstantial, socio-demographic, lifestyle, and health factors, poor cognitive ability in early adulthood was associated with greater erythrocyte sedimentation rate in middle age, β = −.09. Thus, it would appear that not only does systemic inflammation influence cognition, but also that poor cognitive ability earlier in life is associated with inflammation in middle-age.

Research highlights

► Cognition in early adulthood is negatively related to later erthyrocyte sedimentation rate. ► This relationship withstood adjustment for lifestyle confounders. ► Poor cognitive ability earlier in life may increase the risk of inflammation.

Introduction

Systemic inflammation has been implicated in cognitive impairment and dementia. Much of the research has focused on the association between cognition and C-reactive protein (CRP), an acute-phase protein synthesised in the liver. CRP has a variety of functions but is now widely used as a marker of chronic inflammation. A review of six mainly small scale studies of CRP and cognitive disorders revealed that high concentrations of CRP were associated with cognitive decline and dementia (Kuo et al., 2005). Since then, two large scale studies have shown cross-sectional (Schram et al., 2007) and prospective (Laurin et al., 2009) associations between elevated CRP and poorer cognitive function. However, whether a causal pathway from CRP to cognitive function is the only possible explanation for these associations remains undetermined. Recently, in a substantial cross-sectional analyses, CRP was, as hypothesised, negatively related to cognitive performance at age 70; however, the association was largely accounted for by childhood cognitive ability (Luciano et al., 2009). In addition, childhood cognitive performance was a strong predictor of later life inflammation (Luciano et al., 2009). This clearly raises the possibility of reverse causation.

Erythrocyte sedimentation rate (ESR), another marker of inflammation, has largely been ignored in the context of inflammation and cognition. ESR is a measure of the aggregation of erythrocytes and their rate of sedimentation in a test tube, which is determined by the increase in proteins, such as fibrinogen and globulins. As a consequence, ESR is subject to less rapid change than other inflammatory markers, such as CRP, and, accordingly, is likely to be a more stable indicator of systemic inflammation (van Leeuwen and van Rijswijk, 1994). Only one study that we know of has examined the association between ESR and cognitive ability (Karlsson et al., 2010). In a very large sample of Swedish army draftees, a negative cross-sectional association was observed, such that those with higher ESR values, indicative of greater systemic inflammation, showed lower cognitive abilities. Unfortunately, there were no earlier or later measures of cognitive ability or ESR in this study, and so it offers few clues regarding the direction of causality. However, there was an association between childhood socioeconomic position and ESR in young adulthood. Childhood socioeconomic position is associated with cognitive ability (Kaplan et al., 2001) and its inclusion as a covariate in the Swedish study attenuated the association between ESR and cognitive ability (Karlsson et al., 2010). This would imply that an association between cognition and later ESR is a possibility.

The present study examined the relationship between cognition and later ESR in a substantial cohort of US male Vietnam era veterans. Cognitive ability data from early adulthood, i.e., on army enlistment, were available and ESR was measured at a subsequent medical examination 18 years later when the men were middle aged. Due to the richness of the data set we were able to adjust for a range of circumstantial, socio-demographic, behavioural, and health related covariates.

Section snippets

Sample

Participants were Vietnam era male military veterans. The effective sample size was 4256. Ethical approval for the study was given by various bodies, including the US Centers for Disease Control and participants gave informed consent. Details of sampling at each stage of data collection are described more fully elsewhere (Batty et al., 2008, Phillips et al., 2009). Inclusion criteria were: entered military service between January 1, 1965 and December 31, 1971; served only one term of enlistment

Results

The characteristics of the sample are presented in Table 1. For the purposes of the table, the raw ESR summary data are presented. In the linear regression model adjusting only for age, IQ score in young adulthood was associated with ESR in midlife, β = −.20, t = 13.07, p < .001, ΔR2 = .039. Thus, the poorer the cognitive ability, the greater the ESR. The association is illustrated in Fig. 1 which presents the raw ESR data for quartiles of IQ and shows a clear negative dose–response relationship. In

Discussion

The present analyses revealed that cognitive ability in early adulthood was related to ESR in middle age among male Vietnam era veterans: the lower the cognitive ability, the greater the subsequent ESR. To our knowledge, only one previous study has examined the association between cognitive ability and ESR (Karlsson et al., 2010). In a large sample of young Swedish army draftees, cognitive ability and ESR were again found to be negatively related. However, these analyses were cross-sectional.

It

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