BIOMARKER-ORIENTED REHABILITATION IN CHRONIC CEREBRAL ISCHEMIA

Chronic cerebral ischemia (CCI) is a clinically significant form of chronic cerebrovascular disease associated with cognitive decline, impaired daily functioning, and reduced quality of life. In routine clinical practice, the effectiveness of rehabilitation in CCI is often assessed mainly by subjective clinical dynamics, whereas biomarkers and MRI with DTI/SWI may serve as objective indicators of the biological response to restorative treatment.

A prospective controlled comparative study was conducted in 115 patients aged 40-65 years with stage I-II CCI. Allocation to the main group (MG, n=55) and comparison group (CG, n=60) was performed after baseline stratification by disease stage, sex, and age; randomization and complete blinding of outcome assessment were not performed, which was considered a methodological limitation. The MG received a personalized biomarker-oriented program, whereas the CG received standardized therapy. A control group without CCI (n=65) was used only for baseline biomarker comparison. MoCA, MMSE, ADL, IADL, SF-36, IL-6, TNF-alpha, CRP, BDNF, NSE, and D-dimer were assessed at baseline, 3 months, and 6 months; DTI/SWI MRI was performed at baseline and at 6 months.

Compared with stage I CCI, stage II CCI was associated with increased IL-6 (from 5.29 to 6.81 pg/mL), TNF-alpha (from 4.68 to 5.90 pg/mL), CRP (from 3.49 to 5.02 mg/L), NSE (from 18.3 to 23.1 ng/mL), and D-dimer (from 0.308 to 0.423 μg/mL), as well as decreased BDNF (from 11.4 to 9.7 ng/mL; p<0.001). At 6 months, the MG showed more pronounced favorable dynamics than the CG in MoCA (+22.4% vs +7.1%; p<0.001), MMSE (+12.1% vs +4.3%; p<0.001), IL-6 (-34.4% vs -11.1%; p<0.001), BDNF (+23.3% vs +5.8%; p<0.001), NSE (-22.1% vs -5.8%; p<0.001), D-dimer (-27.0% vs -10.8%; p=0.004), FA (+20.5% vs +5.0%; p=0.003), ADL (+39.6% vs +14.3%; p<0.001), IADL (+41.2% vs +16.0%; p<0.001), and SF-36 physical functioning (+51.3% vs +20.2%; p<0.001).

Integrating IL-6, BDNF, NSE, and D-dimer with MoCA/MMSE, ADL/IADL, SF-36, and DTI/SWI MRI makes it possible to objectify CCI severity and monitor rehabilitation effectiveness. The personalized program was associated with more pronounced favorable clinical, laboratory, functional, and neuroimaging dynamics; however, the results should be interpreted cautiously because of the non-randomized design, the absence of complete blinding, and the 6-month follow-up period.