Increase in the Inflammatory Marker GlycA over 13 Years in Young Adults Is Associated with Poorer Cognitive Function in Midlife

Abstract

BackgroundInflammatory markers are elevated in patients with dementia. Evidence for an association between inflammation and cognitive function in dementia-free individuals is sparse, inconsistent, and predominantly restricted to the elderly. Assessment of inflammatory markers in young adults as predictors of cognitive function in midlife, well before the onset of overt dementia, is lacking. Furthermore, rarely has the relation with longitudinal change in inflammatory markers been examined.ObjectiveTo examine the association of the inflammatory markers C-reactive protein (CRP), fibrinogen, white blood cell count (WBC) and GlycA, a novel NMR-determined biomarker of systemic inflammation, measured in young adulthood and of GlycA change over 13 years follow-up with cognitive function in midlife.Methods507 participants of the Jerusalem Lipid Research Clinic (LRC) study were assessed at 3 time points over 18–22 years. First, the inflammatory variables GlycA, CRP, fibrinogen, and WBC were measured in blood samples drawn at ages 28–32. Then, in blood samples drawn a mean 13 years later (range, 12–16 years) at ages 41–46, GlycA was again measured (in 484 individuals). Subsequently at ages 48–52, on average 7 years later, global cognitive function and its five specific component domains were assessed with a NeuroTrax computerized test battery. Multiple regression and multivariable logistic models were applied.ResultsInverse unadjusted associations were shown for baseline levels and longitudinal change in inflammatory markers and measures of cognition. Multiple regression models were adjusted for age at cognitive assessment, sex, socio-demographic characteristics, baseline measures of leisure-time vigorous activity, smoking status and body mass index (BMI) at ages 28–32, change in smoking status and BMI between ages 28–32 and 41–46, and depression assessed at the time of cognitive testing. The highest quintile of GlycA change, but not the baseline inflammation measures, was inversely related to global cognition (standardized β = -.109, p = .011) as well as to the information processing speed and memory domains (standardized β = -.124, p = .008 and-.117, p = .014, respectively). The multivariable-adjusted odds ratio for low ranked global cognitive function (lowest fifth) comparing the extreme quintiles of GlycA change was 4.8 (95%CI, 1.7–13.5, p = .003; p for trend = .031).ConclusionsIn this longitudinal study of a novel systemic inflammatory marker in a population-based cohort of young adults, GlycA increase over 13 years, but not baseline measures of inflammation, was associated with poorer cognitive function in midlife.

The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study

“…For example, it has been shown that systemic inflammation increases with age in a subset of individuals (Jenny et al, 2012). Such a transition to a state of elevated systemic inflammation may occur during midlife in some individuals, or later in life in others (Cohen-Manheim et al, 2015; Metti et al, 2014). Conversely, there is evidence for aging/inflammation phenotypes characterized by reduced inflammation with increasing age (Bettcher et al, 2015; Jenny et al, 2012).…”

Title: Human Serum/Plasma Glycoprotein Analysis by 1H-NMR, an Emerging Method of Inflammatory Assessment

“…However, a higher level of N-acetyl-glycoproteins in patients with psychological suboptimal health has been reported [192]. Another study showed an inverse relationship between GlycA and global cognition and also between information processing speed and memory domains [127].…”

“…GlycA is inversely related to global cognition, information processing speed and memory domains. [127] AD Elevated circulating glycoproteins were associated with the risk for AD and MCI.…”

“…Psychological suboptimal health is a prevalent state with a pathophysiological mechanism that is extremely complicated and poorly understood but inflammation is known to be related. CRP and IL-6 have been associated with cognition, but few studies have measured inflammatory markers as predictors of cognitive function in middle age or of the onset of cognitive complications such as dementia [127]. However, a higher level of N-acetyl-glycoproteins in patients with psychological suboptimal health has been reported [192].…”

The relationship between salivary C-reactive protein and cognitive function in children aged 11–14 years: Does psychopathology have a moderating effect?

“…A study of adults aged 18–82 years reported that CRP was not associated with executive function abilities ( Schuur et al, 2010 ), whilst another large study of 28–91 year olds observed negative correlations between CRP and slower processing speed (but not executive function or memory performance) among African American (but not European American) participants ( Windham et al, 2014 ). Only two studies, both longitudinal, have focused on young individuals from the general population; CRP did not predict memory or executive function in a two-year follow-up of adolescents ( Jonker et al, 2014 ) or global cognition in a 13-year follow-up of young adults ( Cohen-Manheim et al, 2015 ).…”