Serum Inflammatory Markers in Dementia Disorders

Background: Systemic and local inflammatory responses have been proposed as mechanisms in the initiation and progression of dementia. Several studies described increased levels of proinflammatory cytokines in Alzheimer's disease patients. Acute phase reactants such as CRP have been detected within the neuritic plaques and neurofibrillary tangles in the brains of patients with Alzheimer's disease and their elevated levels may predict vascular disease and dementia. Recently, inflammatory markers; α 1-antichymotrypsin, interleukin 6 and to a lesser extent CRP were associated with an increased risk of dementia. Even though several lines of evidence in the literature have shown that inflammation is involved in the pathogenesis of dementia, the results from the evaluation of inflammatory markers in Alzheimer’s disease and vascular dementia patients have been controversial. More over, many of these studies were conducted on CSF. As plasma and CSF levels of many inflammatory markers are significantly interrelated; assessment of such markers in the easily accessible periphery may be as effective as in the CSF and may provide a simple way for the prediction, diagnosis and follow-up of dementia. Aim: The aim of this work was to study inflammatory markers in peripheral blood of patients with dementia in a trial to clarify their role in disease pathogenesis and progression as well as their potential value as diagnostic biological markers and targets of anti-inflammatory therapy for dementia. Subjects and Methods: The study included 20 patients with probable Alzheimer’s disease, 20 patients with probable vascular dementia and 20 healthy normal age and sex matched subjects as a control group. Inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6) and α 1antichymotrypsin (ACT) were measured in the serum of both patient groups and control group. Results: CRP was significantly higher in both Alzheimer disease patients (44.2 ±6.1) and vascular dementia patients (52.3±5.8) compared to controls (10.6 ±0.32) (p<0.01). IL-6 was significantly higher in both Alzheimer disease patients (26.4±4.5) and vascular dementia patients (32.4 ±5.3) compared to controls (9.2±0.5). There was no significant difference between the two patient groups as regards CRP and IL-6 (p>0.05). Serum ACT was significantly higher in Alzheimer’s disease patients (780 ± 19.3) compared to controls (490± 16) and vascular dementia patients (512 ± 16.7) (p<0.01). There was no significant difference between vascular dementia patients and control group as regards ACT ( p>0.01). There was negative correlation between MMSE score and levels of IL-6 and ACT in both patient groups ( r– 0.58, p<0.01). Conclusion: In this study, alterations of the inflammatory markers were detected in peripheral blood of dementia patients denoting that assay of plasma inflammatory markers might provide an insight in the pathogenesis of dementia and might provide an easier and accessible way in the diagnosis and follow up of dementia compared to their assay in CSF. Serum CRP, IL-6 levels were significantly higher in both patients groups compared to the control group. The fact that these changes were found in both Alzheimer’s disease patients and vascular dementia patients emphasize the common pathophysiological mechanisms in the two dementia subtypes. Serum α 1-antichymotrypsin was significantly higher in Alzheimer’s disease patients than in vascular dementia patients denoting its possible value in the differential diagnosis between the two types. The negative correlation between MMSE score and levels of IL-6 and ACT in both patient groups suggest that IL-6 and α 1-ACT may play a role in defining the aggressiveness of dementia and might be used in the follow-up of disease course and effect of therapy. However, continued further research involving larger study population is needed to further establish the significance of these inflammatory markers in the pathogenesis, diagnosis, follow-up and possible therapeutic options for dementia.