Inflammatory Proteins in Plasma and the Risk of Dementia

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Abstract
Neuritic plaques and neurofibrillary tangles are the classic neuropathological features in the brains of patients with Alzheimer disease (AD). Furthermore, inflammation has been demonstrated in AD-affected brains as is indicated by the presence of activated microglia and inflammatory proteins.1 In addition to inflammation within the brain, the peripheral immune system of patients with dementia may be activated as well. This is suggested by cross-sectional studies that reported elevated blood levels of the inflammatory proteins α1-antichymotrypsin (ACT),2-4 C-reactive protein (CRP),5 (IL) 66 in patients with AD compared with control subjects. Prospectively, increased CRP levels have been associated with an increased risk of dementia 25 years later.7 Whether the levels of ACT and IL-6 are increased before the onset of dementia is yet unknown, although the recent finding of an association between the level of IL-6 and cognitive decline suggests elevated IL-6 levels before dementia.8,9 To our knowledge, no studies examined the association between the levels of ACT and IL-6 and dementia in a population-based setting, nor has the association been studied between the levels of other inflammatory proteins, such as cell adhesion molecules (CAMs), and dementia. We investigated the relation between plasma ACT, CRP, IL-6, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and the risk of dementia in a large population-based prospective study.