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Associations of Soluble Inflammatory and Endothelial Activation Biomarkers with Cognitive Function Over Three Years
Naomi K Giesers1, Viktoria Schaeff2,3, Karen Gertz3,4,5
1Department of Neurology, Evangelical Hospital Oldenburg, Carl Von Ossietzky-University, Steinweg 13-17, 26122, Oldenburg, Germany.
Insights
Higher levels of interleukin-6 (IL-6) and vascular cell adhesion molecule (VCAM-1) are linked to worse cognitive function after ischemic stroke. These inflammation markers predict long-term cognitive decline in stroke survivors.
Area of Science:
- Neurology
- Immunology
- Biomarkers
Background:
- Vascular inflammation plays a key role in the development of cognitive impairment following stroke.
- Identifying blood-based biomarkers can help predict cognitive decline in stroke patients.
Purpose of the Study:
- To investigate the association between baseline levels of inflammatory biomarkers (IL-6, VCAM-1, TNF-α) and cognitive function over time in patients with first-ever ischemic stroke.
- To assess the predictive value of these biomarkers for long-term cognitive impairment.
Main Methods:
- Prospective cohort study (Prospective Cohort with Incident Stroke Berlin, NCT01363856) of 570 mild-to-moderate ischemic stroke patients.
- Cognitive function assessed using the Telephone Interview for Cognitive Status-modified (TICS-m) at 1, 2, and 3 years post-stroke.
- Linear mixed-effects models were used to analyze associations, adjusting for demographics, vascular risk factors, stroke severity, and white matter hyperintensity.
Main Results:
- Higher baseline levels of IL-6 and VCAM-1 were significantly associated with lower TICS-m scores over the 3-year follow-up period.
- The association remained significant after adjusting for potential confounders, including white matter hyperintensity burden.
- No significant association was found for TNF-α with cognitive function over time.
Conclusions:
- Elevated baseline levels of IL-6 and VCAM-1 are predictive of poorer cognitive function in the years following a first-ever ischemic stroke.
- These inflammatory biomarkers may serve as potential targets for interventions aimed at preventing or mitigating post-stroke cognitive impairment.
Abstract:
Vascular inflammation is involved in the pathophysiology of post-stroke cognitive impairment. We aimed to assess whether blood-based biomarkers of inflammation and endothelial dysfunction, such as interleukin 6 (IL-6), vascular cell adhesion molecule (VCAM-1), and tumor necrosis factor-alpha (TNF-α), are associated with cognitive function over time in a prospective cohort of first-ever ischemic stroke patients. Data were obtained from the Prospective Cohort with Incident Stroke Berlin (NCT01363856). Cognitive function was assessed with the Telephone Interview for Cognitive Status-modified (TICS-m) at 1 to 3 years of follow-up. Associations of baseline levels of IL-6, VCAM-1, and TNF-α with cognitive function over time were estimated using a linear mixed model adjusted for demographics, education, vascular risk factors, stroke severity, ischemic stroke subtype, and severity of white matter hyperintensity. We included 570 patients with mild-to-moderate ischemic stroke and baseline data on biomarker levels. The mean age was 67 (± 12 SD), 38.6% were female, and the median National Institutes of Health Stroke Scale (NIHSS) was 2 (IQR 1-4). Frequency of cognitive impairment defined as TICS-m score ≤ 31 was 21.9% at year one, 15.4% at year two, and 11.6% at year three. Higher log-transformed levels of IL-6 and VCAM-1 were associated with lower TICS-m scores over time in the adjusted linear mixed model including white matter hyperintensity burden (IL-6: β = -2.0, 95% CI -3.3 to -0.7, p = 0.003; VCAM-1: β = -4.1, 95% CI -7.3 to -1.0, p = 0.01). In patients with mild-to-moderate first-ever ischemic stroke, higher baseline levels of IL-6 and VCAM-1 were associated with lower Telephone Interview for Cognitive Status-modified during 3 years of follow-up.ClinicalTrials.gov Identifier: NCT01363856.
