Abstract 169: Circulating Il-6 And Il-18 Levels Are Associated With The Risk Of Incident Dementia In Patients With Vascular Risk Factors
Background and Purpose: Association between circulating inflammatory marker and future dementia has not been fully investigated. To what extent inflammatory markers impact future dementia beyond small vessel disease (SVD) and brain atrophy on MRI is unknown. We sought to determine the predictive value of circulating inflammation marker (high-sensitivity C-reactive protein [hsCRP], interleukin [IL]-6, and IL-18), when controlling for MRI measures of SVD (lacunar, white matter hyperintensity [WMH]) and brain atrophy on the risk of dementia.
Methods: We enrolled 480 outpatients (median 68 years, male 58%, 12.8±2.4 years of schooling ) who had vascular risk factors but without dementia. At baseline, demographic information, brain MRI, and cognitive function testing were performed. We also measured hsCRP, IL-6, and IL-18. Baseline MRI was used to determine SVD (lacunar and WMH) and atrophy (cortical and subcortical). Cox proportional hazards analysis was performed as predictors of dementia with adjusting for age, gender, APOE4 allele, educational level, history of clinical stroke, conventional vascular risk factors, baseline Mini-Mental State Examination score and MRI-findings.
Results: At end of follow-up (median 7.5 years duration), 40 patients had dementia (Alzheimer disease:21 patients, vascular dementia:16 patients, other type dementia:3 patients) In the age, gender, education level, and APOE4 allele-adjusted models, WMH severity, number of lacunar, atrophy, previous stroke, smoking and baseline MMSE-score were associated with incident dementia. Among inflammatory markers, both IL-6 and IL-18, but not hsCRP, were associated with dementia (IL-6; HR:2.10, 95% CI [1.21-3.58], IL-18; HR:3.32, 95% CI [1.52 -7.28], hsCRP; HR:1.08, 95% CI [0.80-1.46]) (per 1-SD increase in log-transformed inflammatory markers). These associations of both IL-6 and IL-18 with dementia remained significant even after additional adjusting for MRI-findings and confounding variables
Conclusion: Our longitudinal study showed that both IL-6 and IL-18 levels are independently related to the risk of dementia in patients with vascular risk factors. Our results support the hypothesis that inflammation exerts deleterious effects on dementia incidence.
- © 2012 by American Heart Association, Inc.