Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present preliminary study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33–60 years in the first study) were scanned twice, seven years apart. An age-related decrease in MPF was found in global WM, grey matter (GM), and mixed WM–GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2–5%), genu of the corpus callosum (CC) (4.0%), and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM–GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics.

Background: Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression (PCD) using the recently proposed MRI method, macromolecular proton fraction (MPF) mapping. Methods: The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, and 2 severe) at 13.5 ± 10.0 months post-recovery, with matched controls without prior COVID-19 history (n = 19). A post-COVID depression group (PCD, n = 25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n = 38) included participants with neurological COVID-19 complications, excluding clinical depression. Results: Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination, but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of Hamilton scores, PCD presence, and severity. The number of post-COVID symptoms was a significant predictor of PCD presence, while the number of acute symptoms was a significant predictor of PCD severity. Conclusions: This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.

Background: The fundamental question of normal brain myelination in human is still poorly understood. Methods: Age-dependent global, regional, and interhemispheric sex-related differences in brain myelination of 42 (19 men, 23 women) healthy adults (19–67 years) were explored using the MRI method of fast macromolecular fraction (MPF) mapping. Results: Higher brain myelination in males compared to females was found in global white matter (WM), most WM tracts, juxtacortical WM regions, and putamen. The largest differences between men and women, exceeding 4%, were observed bilaterally in the frontal juxtacortical WM; angular, inferior occipital, and cuneus WM; external capsule; and inferior and superior fronto-orbital fasciculi. The majority of hemispheric differences in MPF were common to men and women. Sex-specific interhemispheric differences were found in juxtacortical WM; men more often had left-sided asymmetry, while women had right-sided asymmetry. Most regions of deep gray matter (GM), juxtacortical WM, and WM tracts (except for projection pathways) showed a later peak age of myelination in women compared to men, with a difference of 3.5 years on average. Body mass index (BMI) was associated with higher MPF and later peak age of myelination independent of age and sex. Conclusions: MPF mapping showed high sensitivity to assess sex-related differences in normal brain myelination, providing the basis for using this method in clinics.

The majority of colorectal cancer patients (CRCPs) develop tumors on the background of “metabolically healthy obesity” or metabolic syndrome. The aim of the work was to study the levels of matrix metalloproteinases (MMPs) and heat shock proteins (HSPs) on the surface of blood plasma CD9-positive and FABP4-positive small extracellular vesicles (sEVs) from CRCPs depending on metabolic status and tumor angiogenesis, as well as to evaluate the sEVs markers as predictors of the effectiveness of thermoradiotherapy. In CRCPs, compared with patients with colorectal polyps (CPPs), the proportion of triple positive EVs and EVs with the MMP9+MMP2-TIMP1+ phenotype increased significantly among FABP4-positive EVs (adipocyte-derived EVs), which in general may indicate the overexpression of MMP9 and TIMP1 by adipocytes or adipose tissue macrophages in CRCPs. The results obtained have prospects for use as markers to clarify cancer risk in CPPs. One can assume that for CRCPs with metabolic syndrome or metabolically healthy obesity, it is the FABP4+MMP9+MMP2-TIMP1- population of circulating sEVs that is the most optimal biomarker reflecting tumor angiogenesis. Determining this population in the blood will be useful in monitoring patients after treatment for the early detection of tumor progression. CD9+MMP9+MMP2-TIMP1- and MMP9+MMP2-TIMP1+ subpopulations of circulating sEVs are the most promising predictors of the efficacy of thermoradiation therapy because their levels at baseline differ significantly in CRCPs with different tumor responses.

Insomnia and depression are severe sequelae of COVID-19 and often occur simultaneously. Our study examined associations of insomnia and/or depression with cognitive impairments, white matter changes, and serum biomarkers. In total, 76 long COVID patients and 22 healthy controls were examined using neuropsychiatric (ISI, HADS, and HDRS) and cognitive (MoCA, Stroop, WMT, and TMT) tests, with their blood biomarkers (anti-SARS-CoV-2, BDNF, anti-S100, anti-MBP, and anti-PLP) investigated, and underwent MRI using macromolecular proton fraction (MPF) mapping to quantify myelination. The Insomnia (n = 14), Depression (n = 12), InsDep (comorbid insomnia–depression, n = 13), and PostCovid (long COVID without depression and insomnia, n = 32) groups were identified based on psychiatric/neurological diagnoses and neuropsychiatric assessment. Cognitive performance was most affected in the Insomnia group in the MoCA and CW Stroop tests. The Depression group underperformed in the TMT and W Stroop task; the InsDep group underperformed in the WMT. The Insomnia group showed the greatest demyelination, affecting commissural (CC and tapetum), projection (CR, IC, CST, cerebral peduncles, CP, and ML), and some association pathways (SLF, SFOF), as well as most juxtacortical regions, the thalamus, and the midbrain; these changes correlated with insomnia severity. The Depression and InsDep groups showed smaller but significant overall demyelination correlated with depression severity. The Depression group exhibited the highest MPF decrease in the globus pallidus, putamen, and external capsule, while the InsDep group demonstrated the highest demyelination of the association pathways IFOF, UF, and cingulum. The anti-PLP levels were the highest in the Insomnia group and correlated with both the persistence of insomnia/depression symptoms and demyelination. Demyelination in long COVID is associated with high levels of myelin-specific autoantibodies, but symptoms of insomnia and/or depression are associated with demyelination of a different set of brain structures.

Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity , stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression using recently proposed MRI method, macromolecular proton fraction (MPF) mapping. The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, 2 severe) at 13.5±10.0 months post-recovery, with matched controls without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n=38) included participants with neurological COVID-19 complications, excluding clinical depression. Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of PCD presence and severity according to Hamilton scores. The number of post-COVID symptoms was a significant predictor of PCD presence while the number acute of symptoms was a significant predictor of PCD severity. This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.