Markers of Systemic Inflammation in Assessing the Effectiveness of Neurocognitive Rehabilitation in Aged Patients with Mild Cognitive Impairment

Background: the results of previous studies suggest that the level of activation of inflammatory responses in the periphery correlates with the severity of cognitive impairment in patients with neurodegenerative diseases and can serve as an indicator of the activity of the current pathological process in the brain. Epigenetic factors are suggested to influence the regulation of (neuro)inflammation and cognitive recovery in elderly patients, which opens up a wide spectrum of therapeutic strategies for the treatment of age-associated diseases. 
Objective: to evaluate the possible effects of a comprehensive neurocognitive rehabilitation program on cognitive functioning and blood immunological parameters of elderly patients with mild cognitive impairment (MCI).
Patients and methods: 507 participants of the “Memory Clinic” rehabilitation program with signs of MCI (F06.7, F06.78 according to ICD-10) were examined before the start of neurocognitive training and after its completion (after six weeks). Some patients (11.6%) were observed clinically one year after their inclusion in the program. Cognitive status was assessed using the Modified Hachinski Ischemic Scale, the Mini-Mental State Examination, the Montreal Cognitive Assessment, and the Clock Drawing Test. Enzymatic activity of leukocyte elastase (LE), functional activity of α1-proteinase inhibitor (α1-PI), and levels of antibodies to S-100B and myelin basic protein were determined in patients’ blood. The parameters of healthy donors were used as controls.
Results: immunological examination of patients before the rehabilitation program revealed increased LE and α1-PI activity in the overall group compared to controls (p < 0.001 and p < 0.05). Using a previously developed regression model to identify a high-risk group for Alzheimer’s disease (AD) among patients with MCI, all subjects were divided into two groups (cut-off value p = 0.65). Group 1 (low-risk of AD, n = 330) was characterized by increased LE activity and α1-PI (p < 0.001), Group 2 (highrisk of AD, n = 177) was distinguished by decreased LE activity (p < 0.001) accompanied by high α1-PI activity (p < 0.001). After neurocognitive training, differently directed variants of the dynamics of immunological parameters associated with the severity of patients’ cognitive impairment on psychometric scales were identified in each group. For the most of the examined patients (61.3%) the training program turned out to be effective, which was confirmed by the positive dynamics of the psychometric scores and relative normalization of the blood inflammatory markers (p < 0.05). The highest effect of the rehabilitation program was typical for patients not included in the high-risk group for AD (p < 0.001). Follow-up examination revealed stabilization of cognitive functioning in 93.2% of those examined, most of whom were patients with an initially low risk of developing the disease (p < 0.01).
Conclusion: neurocognitive rehabilitation of patients with MCI carried out in the “Memory Clinic” conditions can be considered as a social epigenetic factor modulating the current pathological process in patients with cognitive disorders, which is confirmed by objective immunological markers.

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