Serum IL‐8 is a marker of white‐matter hyperintensities in patients with Alzheimer's disease

Zhu, Yanan; Chai, Yuek Ling; Hilal, Saima; Ikram, M. Kamran; Venketasubramanian, Narayanaswamy; Wong, Boon Seng; Chen, Christopher; Lai, Mitchell K.P.

doi:10.1016/j.dadm.2017.01.001

Cited by 49 publications

(35 citation statements)

References 48 publications

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“…A recent study showed that serum IL-8 concentrations were associated with (Fig. 2 WMH on T2-weighted MRI in patients with AD [50]. The present study adds evidence that peripheral IL-8 concentrations in AD might partly indicate neutrophil chemoattractant and activator functions, which predict a decline in executive function.…”

Section: Discussionsupporting

confidence: 70%

A peripheral neutrophil-related inflammatory factor predicts a decline in executive function in mild Alzheimer’s disease

Bawa

Krance

Herrmann

et al. 2020

J Neuroinflammation

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Background: Studies suggest a role of the innate immune system, including the activity of neutrophils, in neurodegeneration related to Alzheimer's disease (AD), but prospective cognitive data remain lacking in humans. We aimed to investigate the predictive relationship between neutrophil-associated inflammatory proteins in peripheral blood and changes in memory and executive function over 1 year in patients with AD. Methods: Participants with AD were identified from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Neutrophil gelatinase-associated lipocalin (NGAL), myeloperoxidase (MPO), interleukin-8 (IL-8), macrophage inflammatory protein-1 beta (MIP-1β), and tumor necrosis factor (TNF) were assayed by luminex immunofluorescence multiplex assay at baseline. Confirmatory factor analysis was used to test an underlying neutrophil associated plasma inflammatory factor. Composite z-scores for memory and executive function were generated from multiple tests at baseline and at 1 year. A multiple linear regression model was used to investigate the association of the baseline inflammatory factor with changes in memory and executive function over 1 year. Results: Among AD patients (n = 109, age = 74.8 ± 8.1, 42% women, Mini Mental State Examination [MMSE] = 23.6 ± 1.9), the neutrophil-related inflammatory proteins NGAL (λ = 0.595, p < .001), MPO (λ = 0.575, p < .001), IL-8 (λ = 0.525, p < .001), MIP-1β (λ = 0.411, p = .008), and TNF (λ = 0.475, p < .001) were found to inform an underlying factor. Over 1 year, this inflammatory factor predicted a decline in executive function (β = − 0.152, p = 0.015) but not memory (β = 0.030, p = 0.577) in models controlling for demographics, brain atrophy, white matter hyperintensities, the ApoE ε4 allele, concomitant medications, and baseline cognitive performance.

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Section: Discussionsupporting

confidence: 70%

A peripheral neutrophil-related inflammatory factor predicts a decline in executive function in mild Alzheimer’s disease

Bawa

Krance

Herrmann

et al. 2020

J Neuroinflammation

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“…46,47 WMH might be a consequence of neuroinflammation. 48 Our neuropathology data showed high agreement between our clinical diagnosis and the definitive pathologic diagnosis. Although our data showed that 100% of homozygous APOE e4 carriers had CAA compared to 64% of heterozygotes, it did not show that WMH burden was associated with worse cognition in people with 2 alleles, and should be interpreted with caution due to the small sample size.…”

Section: Discussionsupporting

confidence: 68%

APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia

et al. 2019

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ObjectiveTo determine if APOE ε4 influences the association between white matter hyperintensities (WMH) and cognitive impairment in Alzheimer disease (AD) and dementia with Lewy bodies (DLB).MethodsA total of 289 patients (AD = 239; DLB = 50) underwent volumetric MRI, neuropsychological testing, and APOE ε4 genotyping. Total WMH volumes were quantified. Neuropsychological test scores were included in a confirmatory factor analysis to identify cognitive domains encompassing attention/executive functions, learning/memory, and language, and factor scores for each domain were calculated per participant. After testing interactions between WMH and APOE ε4 in the full sample, we tested associations of WMH with factor scores using linear regression models in APOE ε4 carriers (n = 167) and noncarriers (n = 122). We hypothesized that greater WMH volume would relate to worse cognition more strongly in APOE ε4 carriers. Findings were replicated in 198 patients with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI-I), and estimates from both samples were meta-analyzed.ResultsA significant interaction was observed between WMH and APOE ε4 for language, but not for memory or executive functions. Separate analyses in APOE ε4 carriers and noncarriers showed that greater WMH volume was associated with worse attention/executive functions, learning/memory, and language in APOE ε4 carriers only. In ADNI-I, greater WMH burden was associated with worse attention/executive functions and language in APOE ε4 carriers only. No significant associations were observed in noncarriers. Meta-analyses showed that greater WMH volume was associated with worse performance on all cognitive domains in APOE ε4 carriers only.ConclusionAPOE ε4 may influence the association between WMH and cognitive performance in AD and DLB.

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“…Transient cognitive impairment was most prevalent in the first week post-stroke (39%) compared with after this week (19%) [21]. It was found that the serum level of IL-8 was significantly elevated in the plasma of the patients in the first 48 h post stroke in comparison to control group in this study which was in concordance with [6,22]. This could be attributed to the fact that astrocytes induce IL-8 expression in the area of brain damage.…”

Section: Discussionsupporting

confidence: 82%

Post-stroke executive dysfunction and verbal fluency negatively correlated to IL8

Shaheen

Daker

Abbass

et al. 2019

Egypt J Neurol Psychiatry Neurosurg

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Background: Patients with acute ischemic stroke are at a higher risk of developing cognitive impairment which could be often attributed to cytokine activation. Objectives: To explore the relationship between the cognitive performance and the inflammatory markers in the ischemic stroke patients at the early stage. Patients and methods: A cross-sectional case-control study was performed on 44 ischemic stroke patients. The patients underwent the following battery of evaluation: (A) assessment of stroke disability by modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS). (B) neuropsychological evaluation using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) scale, trail making test (TMT), and Controlled Oral Word Association Test (COWAT). (C) Assessment of depression was done by using Beck Depression Inventory (BDI). Measurement of the serum levels of ESR, C-reactive protein, and IL-8 was done. This study included 44 ages, sex, and educational level matched controls for comparison of neuropsychological tests and serum level of IL-8. Results: The patients showed worse performance in neuropsychological tests (MMSE, MoCA, COWAT, TMT) than the controls. There was a significant negative correlation between the serum level of IL-8 and (MoCA) (r = − 0.43, p = 0.004), verbal fluency (r = − 0.56, p < 0.001), and positive significant correlation between IL8 and executive functions (r = 0.61, p < 0.001). Conclusion: The cognitive impairment in early acute ischemic stroke is highly correlated to the serum level of IL-8.

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Serum IL‐8 is a marker of white‐matter hyperintensities in patients with Alzheimer's disease

Cited by 49 publications

References 48 publications

A peripheral neutrophil-related inflammatory factor predicts a decline in executive function in mild Alzheimer’s disease

A peripheral neutrophil-related inflammatory factor predicts a decline in executive function in mild Alzheimer’s disease

APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia

Post-stroke executive dysfunction and verbal fluency negatively correlated to IL8

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