Dataset Information

Repeated systemic inflammation was associated with cognitive deficits in older Britons.

ABSTRACT:

Introduction

The relationship of C-reactive protein (CRP) to cognition in the older old group (?75 years) has recently been found positive on both sides of the Atlantic. We hypothesized that higher levels of CRP and fibrinogen are related to worse episodic memory throughout later life (?50 years).

Methods

Data are drawn from older Britons free of dementias in the English Longitudinal Study of Aging 2004-2013. We applied growth trajectory models to repeated observations of episodic memory, CRP, and fibrinogen levels (and sociodemographic confounders). We accounted for practice effects in repeated tests of cognition.

Results

Higher levels of both inflammatory markers were associated with worse episodic memory, where a fibrinogen effect is evident throughout later life (coefficient -0.154; 95% confidence interval [CI] -0.254 to -0.054). Most importantly, the CRP effect is strongly negative among the older old group (coefficient -0.179; CI -0.320 to -0.038).

Discussion

Higher levels of fibrinogen are detrimental to older people's cognition, and among the older old, raised CRP levels are comparably deleterious. Repeated measures of inflammation can be considered in clinical practice as part of a response to the challenge of dementias.

SUBMITTER: Tampubolon G

PROVIDER: S-EPMC4879642 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Repeated systemic inflammation was associated with cognitive deficits in older Britons.

Tampubolon Gindo G

Alzheimer's & dementia (Amsterdam, Netherlands) 20151228

<h4>Introduction</h4>The relationship of C-reactive protein (CRP) to cognition in the older old group (≥75 years) has recently been found positive on both sides of the Atlantic. We hypothesized that higher levels of CRP and fibrinogen are related to worse episodic memory throughout later life (≥50 years).<h4>Methods</h4>Data are drawn from older Britons free of dementias in the English Longitudinal Study of Aging 2004-2013. We applied growth trajectory models to repeated observations of episodic ...[more]

PMID: 27239544

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Project description:Objectives/Background: Systemic inflammation can affect cognitive performance over time. The current study examined associations between systemic inflammation and cognitive performance among African Americans and Whites urban adults, stratifying by sex, and age group and by race. Patients/Methods: Among 1,555-1,719 White and African-American urban adults [Agebase: 30-64y, 2004-2013, mean±SD follow-up time(y): 4.64 ± 0.93y], conducted linear mixed-effects regression models were conducted to test associations of inflammatory markers [C-reactive protein, Erythrocyte Sedimentation Rate (ESR), albumin, iron, and an inflammation composite score (ICS)] with longitudinal cognitive performance. Results: Among key findings, CRP was linked to poorer baseline mental status among younger women (≤50y, γ01 = -0.03 ± 0.01, p = 0.002) and poorer attention in older women (>50y, γ01 = -0.024 ± 0.007, p < 0.004) and African-Americans (γ01 = -0.029 ± 0.008, p < 0.001). ESR was related to faster decline on verbal memory among older men (>50y, γ11 = -0.008 ± 0.003, P = 0.009); with poorer performance on attention tests overall (γ01 = -0.010 ± 0.003, P = 0.003) and among African-Americans (γ01 = -0.013 ± 0.004, P = 0.002); on verbal fluency among older women (>50y,γ01 = -0.037 ± 0.013, P = 0.004) and on executive function: overall (γ01 = +0.62 ± 0.21, P = 0.004), older men (>50y, γ01 = +1.69 ± 0.53, P = 0.001) and African-Americans (γ01 = +0.84 ± 0.28, P = 0.002). Albumin was linked to slower attention decline among older men (>50y, γ11 = +0.329 ± 0.103, P = 0.009), over-time improvement in executive function overall (γ11 = -6.00 ± 2.26, P = 0.008), and better baseline psychomotor speed among African-Americans (γ01 = +0.56 ± 0.19, P = 0.003). Finally, ICS predicted faster decline on visual memory/visuo-constructive abilities among older men (>50y, γ11 = +0.17 ± 0.06, p = 0.003). Conclusion: In sum, strong associations between systemic inflammation and longitudinal cognitive performance were detected, largely among older individuals (>50y) and African-Americans. Randomized trials targeting inflammation are warranted.

Project description:Background & aimsCognitive dysfunction is an increasingly recognised manifestation of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanistic link remains unclear. The aim of this study was to investigate the hypothesis that experimental MASLD leads to cognitive dysfunction via systemic inflammation and neuroinflammation.MethodsTwenty male Sprague Dawley rats were randomised to a high-fat high-cholesterol (HFHC) diet to induce MASLD, or a standard diet (n = 10/group), for 16 weeks. Assessments included: MASLD severity (histology), neurobehaviour, inflammation (liver, plasma and cerebrospinal fluid), brain microglia and astrocyte activation, and synaptic density.ResultsThe HFHC diet induced MASLD with extensive steatosis and lobular inflammation without fibrosis. Several plasma cytokines were elevated (CXCL1, IL-6, IL-17, MIP-1α, MCP-1, IL-10; all p <0.05) and correlated with increases in hepatic chemokine gene expression. Cerebrospinal fluid concentrations of CXCL1 were elevated (p = 0.04). In the prefrontal brain cortex, we observed a 19% increase in microglial activation confirmed by Iba1 immunohistochemistry (p = 0.03) and 3H-PK11195 autoradiography (p <0.01). In parallel, synaptic density was reduced to 92%, assessed by 3H-UCB-J autoradiography (p <0.01). MASLD animals exhibited impaired memory to previously encountered objects in the novel object recognition test (p = 0.047) and showed depression-like behaviour evidenced by increased immobility time (p <0.01) and reduced swimming time (p = 0.03) in the forced swim test.ConclusionsExperimental non-fibrotic MASLD, as a model to reflect the early stage of human disease, results in cognitive impairment and depression-like behaviour. This is associated with an inflammatory phenotype not only in the liver but also in the plasma and brain, which together with diminished synaptic density, provides a pathophysiological link between liver disease and cognitive dysfunction in MASLD.Impact and implicationsCognitive dysfunction is an increasingly recognised comorbidity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), yet the underlying mechanisms remain unclear. This study provides evidence of impaired memory and depression-like symptoms in early experimental MASLD and indicates that hepatic inflammation may drive a systemic inflammatory response, resulting in neuroinflammation and reduced brain synaptic density. The evidence of impaired memory in MASLD and establishing its underlying pathophysiological link provides insights that could guide the development of potential new treatments for this increasingly common condition in people of working age. The study also emphasises the need to develop better tools for clinical cognitive testing, which will enable physicians to assess and manage brain dysfunction early in MASLD.

Dataset Information

Repeated systemic inflammation was associated with cognitive deficits in older Britons.

Introduction

Methods

Results

Discussion

Publications

Repeated systemic inflammation was associated with cognitive deficits in older Britons.

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