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

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.

Biomarkers of neurodegeneration in post-traumatic stress disorder: an integrative review

“…In the current review, these findings were replicated in the context of possible links with neurodegeneration, with results specifically implicating CRP, IL-6 and soluble TNF-α receptor II. Of these three inflammatory markers, CRP has been associated with progression to dementia even after adjustment for confounding factors [85], while IL-6 has been specifically associated with vascular dementia [86].…”

Risk of dementia or cognitive impairment in COPD patients: A meta-analysis of cohort studies

“…Oxidative stress caused by systemic inflammation and hypoxia was considered to be one of the causes of dementia, which may be a mechanism that links cardiopulmonary pathology with neurocognitive impairment (Cheung et al, 2018). Inflammatory markers such as the levels of interleukin (IL)-6, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) also have been reported to be elevated in patients with COPD (Deveci et al, 2010;Custodero et al, 2022). In addition, a study (Ranzini et al, 2020) showed patients with COPD may show cerebral perfusion alterations as a consequence of hypoxemia, which is an abnormal decrease in oxygen in the blood, and these changes could lead to cognitive impairment.…”

Exploration of acupuncture therapy in the treatment of mild cognitive impairment based on the brain-gut axis theory

“…We acknowledge the importance to the vascular contributions to cognitive function ( Custodero et al, 2022 ; Kiss et al, 2022 ; Montagne et al, 2022 ). Acupuncture was found can alleviate cognitive function in Vascular dementia (VD), but the underlying mechanisms are still unclear ( Cao et al, 2013 ).…”