Systemic Inflammatory Markers in Age-Associated Cognitive Impairment and Alzheimer’s Disease

Abstract

Objectives. A set of immune markers reflecting different branches of multicomponent inflammatory reactions were assessed in mild cognitive impairment syndrome of the amnestic type (aMCI) in comparison with patients with Alzheimer’s disease (AD). A total of 67 patients aged 72 [63; 77] years with aMCI and 91 patients aged 74 [68; 79] years with AD were investigated. aMCI was diagnosed in accordance with the Petersen et al. (1999) criteria and the Dubois et al. (2014) criteria. Diagnoses of AD were made on the basis of ICD-10 and NINCDS-ADRDA criteria. The severity of dementia was determined on the basis of clinical signs using the CDR (Clinical Dementia Rating) scales and total Mini Mental State Examination (MMSE) scores. The control group consisted of 38 subjects with age and gender comparable to those of the study groups. Immunobiochemical investigations were performed using plasma. Leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activities were estimated spectrophotometrically and interleukin-6 (IL-6) and C-reactive protein (CRP) levels were measured using an immunoenzyme method. Results. A significant decrease in LE activity was seen in the AD group (p < 0.0001), along with increases in the activity/ levels of acute-phase proteins (α1-PI and CRP) and IL-6 (p < 0.0001, p < 0.05, and p < 0.01, respectively). Clinical-biochemical correlations were found between CDR, MMSE, and LE activity (r = –0.38, r = 0.31, p < 0.05), i.e., the more severe the cognitive decline in the state of dementia, as reflected in the MMSE and clinical symptoms, the lower the level of LE activity. Among patients with aMCI, there were significant increases in the activity/levels of α1-PI and IL-6 (p < 0.0001, p < 0.01), while only 30% of patients showed the spectrum of inflammatory markers typical of patients with AD. Conclusions. The results of this comparative analysis of the spectrum of inflammatory markers in patients with aMCI and AD suggest that about a third of aMCI patients constitute a group at extremely high risk of developing AD and require follow-up with regular assessment of the state of cognitive functions and, perhaps, of preventive therapy.