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Meta-Analysis
. 2022 Jun;44(3):1373-1392.
doi: 10.1007/s11357-022-00556-w. Epub 2022 Apr 29.

Role of inflammatory markers in the diagnosis of vascular contributions to cognitive impairment and dementia: a systematic review and meta-analysis

Carlo Custodero  1 , Alessandro Ciavarella  1   2 , Francesco Panza  3 , Davide Gnocchi  1 , Gennaro M Lenato  1 , Juhan Lee  4 , Antonio Mazzocca  1 , Carlo Sabbà  1 , Vincenzo Solfrizzi  5
Affiliations
Meta-Analysis

Role of inflammatory markers in the diagnosis of vascular contributions to cognitive impairment and dementia: a systematic review and meta-analysis

Carlo Custodero et al. Geroscience. 2022 Jun.

Abstract

Vascular contribution to cognitive impairment and dementia (VCID) is a clinical label encompassing a wide range of cognitive disorders progressing from mild to major vascular cognitive impairment (VCI), which is also defined as vascular dementia (VaD). VaD diagnosis is mainly based on clinical and imaging findings. Earlier biomarkers are needed to identify subjects at risk to develop mild VCI and VaD. In the present meta-analysis, we comprehensively evaluated the role of inflammatory biomarkers in differential diagnosis between VaD and Alzheimer's disease (AD), and assessed their prognostic value on predicting VaD incidence. We collected literature until January 31, 2021, assessing three inflammatory markers [interleukin(IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α] from blood or cerebrospinal fluid (CSF) samples. Thirteen cross-sectional and seven prospective studies were included. Blood IL-6 levels were cross-sectionally significantly higher in people with VaD compared to AD patients (SMD: 0.40, 95% CI: 0.18 to 0.62) with low heterogeneity (I2: 41%, p = 0.13). Higher IL-6 levels were also associated to higher risk of incident VaD (relative risk: 1.28, 95% CI: 1.03 to 1.59, I2: 0%). IL-6 in CSF was significantly higher in people with VaD compared to healthy subjects (SMD: 0.77, 95% CI: 0.17 to 1.37, I2: 70%), and not compared to AD patients, but due to limited evidence and high inconsistency across studies, we could not draw definite conclusion. Higher blood IL-6 levels might represent a useful biomarker able to differentiate people with VaD from those with AD and might be correlated with higher risk of future VaD.

Keywords: Alzheimer’s disease; C-reactive protein; Interleukin-6; Tumor necrosis factor-α; Vascular contributions to cognitive impairment and dementia.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flowchart of identification and selection of eligible studies
Fig. 2
Fig. 2
Difference in blood interleukin-6 levels between subjects with vascular dementia and controls (A) or those with Alzheimer’s disease (B); pooled hazard ratios for interleukin-6 and incident vascular dementia (C)
Fig. 3
Fig. 3
Difference in blood C-reactive protein levels between subjects with vascular dementia and controls (A) or those with Alzheimer’s disease (B); pooled hazard ratios for C-reactive protein and incident vascular dementia (C)
Fig. 4
Fig. 4
Difference in blood tumor necrosis factor-α levels between subjects with vascular dementia and controls (A) or those with Alzheimer’s disease (B)
Fig. 5
Fig. 5
Difference in cerebrospinal fluid interleukin-6 levels between subjects with vascular dementia and controls (A) or those with Alzheimer’s disease (B)
See this image and copyright information in PMC

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