Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function

Wersching, Heike; Duning, Thomas; Lohmann, Hubertus; Mohammadi, Siawoosh; Stehling, Christoph; Fobker, Manfred; Conty, M.; Minnerup, Jens; Ringelstein, E.B.; Berger, Klaus; Deppe, Michael; Knecht, Stefan

doi:10.1212/wnl.0b013e3181d7b45b

Cited by 199 publications

(190 citation statements)

References 40 publications

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“…Depression was defined by history, intake of antidepressants, or scores higher than 17 on the Beck Depression Inventory. Education was assessed as categorical variable (5 vs 7 vs 9 years of secondary school vs tertiary education according to the German educational system (Wersching et al, 2010).…”

Section: Risk Factor Assessmentmentioning

confidence: 99%

Impact of Common KIBRA Allele on Human Cognitive Functions

Wersching

Guske

Hasenkamp

et al. 2011

Neuropsychopharmacol

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The rs17070145 polymorphism (C-T substitution, intron 9) of the KIBRA gene has recently been associated with episodic memory and cognitive flexibility. These findings were inconsistent across reports though, and largely lacked gene-gene or gene-environment interactions. The aim of the present study was to determine the impact of the rs17070145 polymorphism on clinically relevant cognitive domains and its interaction with the modifiers 'lifestyle' and 'cardiovascular risk factors'. Five-hundred forty-five elderly volunteers (mean age 64 years, ± 7 years, 56% women) accomplished a comprehensive cognitive testing. Principal component analysis was used to reveal the internal structure of the data, rendering four composite scores: verbal memory, word fluency, executive function/psychomotor speed, and working memory. Lifestyle was assessed with a detailed questionnaire, age-associated risk factors by clinical interview and examination. There was no main effect of the rs17070145 genotype on any cognitive composite scores. However, we found worse performance in executive functions for T-allele carriers in the presence of arterial hypertension (b ¼ À0.365, p ¼ 0.0077 and 0.031 after Bonferroni correction). This association was further modified by gender, showing the strongest association in hypertensive females (b ¼ À0.500, p ¼ 0.0072 and 0.029 after Bonferroni correction). The effect of KIBRA on cognitive function seems to be complex and modified by gender and arterial hypertension.

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Section: Risk Factor Assessmentmentioning

confidence: 99%

Impact of Common KIBRA Allele on Human Cognitive Functions

Wersching

Guske

Hasenkamp

et al. 2011

Neuropsychopharmacol

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“…9 WMH are related to slow gait in older adults. 10,11 In regions that are free of WMH, which we refer to here as normal-appearing white matter (NAWM), subtle changes are detected on diffusion tensor imaging (DTI) as a reduction in fractional anisotropy of NAWM (NAWM-FA), denoting loss of myelin and astrogliosis at the microstructural level.…”

mentioning

confidence: 94%

Slow gait, white matter characteristics, and prior 10-year interleukin-6 levels in older adults

et al. 2016

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Objective: To examine the relationship between gait speed and prior 10 years interleukin-6 (IL-6) burden in older adults. We then assessed whether white matter characteristics influence this relationship.Methods: In 179 community-dwelling older adults, gait speed was assessed on an automated walkway and serum IL-6 was assayed on ELISA. Concurrently, white matter characteristics were assessed on MRI by quantifying volume of white matter hyperintensities (WMH), a marker of small vessel disease, and normal-appearing white matter on fractional anisotropy (NAWM-FA), a marker of axonal integrity. IL-6 was assayed at regular intervals at gait assessment and over the prior 10 years and estimates of sustained 10-year IL-6 exposure and the rate of change in IL-6 over 10 years were obtained. Multivariate linear regressions were used to examine the relationships among sustained IL-6 exposure, rate of change in IL-6, gait speed, and white matter characteristics.Results: In this sample (age 83 years, 58% female, 41% black, gait speed 0.9 m/s), higher sustained IL-6 levels, but not the rate of change in IL-6 or IL-6 at gait assessment, was significantly related to slower gait (b 5 20.27, p , 0.001) and to higher WMH (b 5 0.23, p 5 0.002), but not NAWM-FA, withstanding covariate adjustments. WMH accounted for 30% attenuation in the relationship between higher sustained IL-6 levels and slower gait speed (p 5 0.043) in the mediation analyses.Conclusions: Sustained exposure to high IL-6 over 10 years rather than the rate of change in or an isolated high IL-6 level may adversely affect gait speed by influencing cerebral WMH. Increased levels of inflammatory cytokines such as interleukin-6 (IL-6) are cross-sectionally and longitudinally associated with poor physical function in older adults.1-5 IL-6 assayed at regular intervals over a long-term period may better capture sustained IL-6 exposure and rate of change rather than random assays spread apart over time. It is not known whether the sustained longterm exposure to IL-6 or rate of change in IL-6 contributes to the relationship between IL-6 and gait speed beyond a single concurrent indicator of inflammation.Higher IL-6 is linked to greater volume of white matter hyperintensities (WMH) on MRI in most studies [6][7][8] but not in all. 9 WMH are related to slow gait in older adults. 10,11 In regions that are free of WMH, which we refer to here as normal-appearing white matter (NAWM), subtle changes are detected on diffusion tensor imaging (DTI) as a reduction in fractional anisotropy of NAWM (NAWM-FA), denoting loss of myelin and astrogliosis at the microstructural level.

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“…The increased excitotoxicity and neuroinflammatory markers in the frontal cortex of postmortem bipolar patients suggest that their upregulation might lead to cell death and could account for brain atrophy and cognitive decline [15]. Furthermore, increasing CRP is associated with cerebral microstructural disintegration that mainly affects frontal pathways and corresponding executive function [16], which cross-cultural comparisons of Wisconsin Card Sorting Test (WCST) performance have indicated is inherent to bipolar disorder [17]. However, the relationship between circulating high-sensitivity CRP (hs-CRP) and volumetric changes in the brain in bipolar disorder remains unclear.…”

Section: Introductionmentioning

confidence: 99%

The Link between High-Sensitivity C-Reactive Protein and Orbitofrontal Cortex in Euthymic Bipolar Disorder

Chung

Huang

et al. 2013

Neuropsychobiology

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Objective: C-reactive protein (CRP), a marker of underlying low-grade inflammation, has been associated with the pathophysiology of bipolar disorder. Additionally, bipolar disorder may be accompanied by functional or structural cerebral alterations. We attempted to discover whether serum high-sensitivity CRP (hs-CRP) levels are linked to the structural volume change of a specific brain region along with cognitive performance. Methods: We recruited 17 physically healthy patients with bipolar I disorder (DSM-IV), aged 18-45 years and euthymic, to undergo the Wisconsin Card Sorting Test (WCST) and volumetric magnetic resonance imaging at 1.5 T. The analytic method was based on the hidden Markov random field model with an expectation-maximization algorithm, and the volume of each brain region was presented as a percentage of the total intracranial volume. Results: Among the various regions, only the orbitofrontal cortex had a significantly negative correlation with serum hs-CRP levels after adjustment for age and gender (left and right orbitofrontal cortex: r = -0.62, p < 0.01, and r = -0.67, p < 0.005, respectively). Regarding cognitive function, poor WCST performance was also associated with certain subregions of the orbitofrontal cortex. Conclusion: Elevation of serum hs-CRP levels, an indicator of inflammation, may be associated with reduced volume of the orbitofrontal cortex. Persistent inflammation in the euthymic phase of bipolar disorder may involve the pathogenesis or pathophysiology of alteration of the frontal pathway.

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Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function

Abstract: These data suggest that low-grade inflammation as assessed by high-sensitivity C-reactive protein is associated with cerebral microstructural disintegration that predominantly affects frontal pathways and corresponding executive function.

Cited by 199 publications

References 40 publications

Impact of Common KIBRA Allele on Human Cognitive Functions

Impact of Common KIBRA Allele on Human Cognitive Functions

Slow gait, white matter characteristics, and prior 10-year interleukin-6 levels in older adults

The Link between High-Sensitivity C-Reactive Protein and Orbitofrontal Cortex in Euthymic Bipolar Disorder

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