SERUM IL-8 IS A POTENTIAL INFLAMMATORY MARKER OF WHITE MATTER HYPERINTENSITIES IN COGNITIVE IMPAIRMENT AND DEMENTIA

Abstract

As neuroinflammation is well-known to be involved in the pathogenesis of dementia1, the present study aimed to measure baseline serum inflammatory markers in a Singaporean cohort of cognitive impairment no dementia (CIND), which is a pre-dementia stage, and Alzheimer's disease (AD). Vascular disease has been suggested to play a role in cognitive impairment and dementia2. In previous inflammatory marker studies, the impact of cerebrovascular disease (CeVD) was generally neglected. So in our study of serum inflammatory markers, the association with CeVD was also investigated. Serum samples from 97 patients with AD, 141 with CIND and 79 non-cognitively impaired participants (NCI) were measured for interleukin 6 (IL-6), IL-8, monocyte chemotactic protein 1 (MCP-1) and Tumor Necrosis Factor α (TNFα) levels. CeVD cases were diagnosed with the assistance of MRI markers regarding to presence of lacunes, cortical infarcts and white matter hyperintensities (WMH). There was no significant change for IL-6 and MCP-1 levels among the three groups. Both IL-8 and TNFα were highest in AD and lowest in NCI, with intermediate levels in CIND. After controlling for covariates, high concentrations of IL-8 remain associated with both disease groups, especially in the cases with CeVD, namely: CIND with CeVD (odds ratios [OR] 4.96; 95% CI 1.70 - 14.53) and AD CeVD (OR 9.17; 95% CI 1.72 - 49.06). Among the different CeVD, only WMH was associated with higher IL-8 levels (OR: 2.58; 95% CI:1.36 – 4.87). Serum IL-8 may be a useful peripheral biomarker for cognitive decline and dementia in subjects with WMH. 1. Heneka MT, Carson MJ, Khoury JE, et al. Neuroinflammation in Alzheimer's disease. The Lancet Neurology. 2015;14(4):388-405. 2. Kling MA, Trojanowski JQ, Wolk DA, Lee VM, Arnold SE. Vascular disease and dementias: paradigm shifts to drive research in new directions. Alzheimer's & dementia: the journal of the Alzheimer's Association. Jan 2013;9(1):76-92.