We implemented a multimodal approach to examine associations between structural and neurochemical changes that could signify neurodegenerative processes related to mild cognitive impairment (MCI). Fifty-nine older adults (60–85 years; 22 MCI) underwent whole-brain structural 3T MRI (T1W, T2W, DTI) and proton magnetic resonance spectroscopy (¹H-MRS). The regions of interest (ROIs) for ¹H-MRS measurements were the dorsal posterior cingulate cortex, left hippocampal cortex, left medial temporal cortex, left primary sensorimotor cortex, and right dorsolateral prefrontal cortex. The findings revealed that subjects in the MCI group showed moderate to strong positive associations between the total N-acetylaspartate to total creatine and the total N-acetylaspartate to myo-inositol ratios in the hippocampus and dorsal posterior cingulate cortex and fractional anisotropy (FA) of WM tracts crossing these regions—specifically, the left temporal tapetum, right corona radiata, and right posterior cingulate gyri. In addition, negative associations between the myo-inositol to total creatine ratio and FA of the left temporal tapetum and right posterior cingulate gyri were observed. These observations suggest that the biochemical integrity of the hippocampus and cingulate cortex is associated with a microstructural organization of ipsilateral WM tracts originating in the hippocampus. Specifically, elevated myo-inositol might be an underlying mechanism for decreased connectivity between the hippocampus and the prefrontal/cingulate cortex in MCI.

Background: Diffusion-prepared pseudo-continuous arterial spin labelling (DP-pCASL) can quantify the cerebral blood flow (CBF) and the water exchange rate (kw) across the blood–brain barrier (BBB). Little is known about the BBB water exchange in major depressive disorder (MDD). Objective: We aimed to explore the associations between kw, CBF, peripheral inflammation, and MDD. Methods: Using DP-pCASL, we measured the global and selected regional kw and CBF together with blood plasma levels of lipopolysaccharide (LPS) and inflammatory cytokines in 85 patients with MDD and 51 controls. Results: The global CBF was significantly lower in MDD patients compared with controls (means of 51 and 57 mL/100 g/min, respectively; p = 0.006), with similar reductions found in the dorsolateral and ventromedial prefrontal, anterior, and posterior cingulate regions, while no differences were found in the amygdala and the isthmic cingulate. There were no differences in the kw between groups globally (means of 128 min⁻¹; p = 0.958) and in the studied regions. Among MDD patients, the kw was weakly correlated with the MADRS scores (r = 0.231, p = 0.034). There were no associations between kw, CBF, and inflammatory markers (LPS, IL-6, IL-10, TNF-α, IFN-γ). Logistic regression showed that a combination of the regional CBF < 59.22 mL/100 g/min together with LPS > 143.58 pg/mL and/or IL-10 > 0 pg/mL distinguished MDD patients from controls with a moderate accuracy of 83.1% (sensitivity = 94.1%, specificity = 64.7%, AUC = 0.876). Conclusions: DP-pCASL imaging confirmed previous findings of reduced CBF in MDD, which together with LPS and IL-10 concentrations were independent significant predictors of MDD. However, no changes in the BBB water exchange were found, suggesting that it may not be as significant as CBF in MDD pathophysiology.

Background: Inflammatory mechanisms contribute to major depressive disorder (MDD) in a subset of patients. Lipopolysaccharide (LPS), a potent inflammatory endotoxin, can induce depressive-like symptoms, but its relationship with specific depressive symptom profiles remains unclear. Methods: In total, 95 adults with MDD (mean age was 44 ± 14 years) were recruited from psychiatric inpatient and outpatient services. Depressive symptom severity was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS). Serum concentrations of LPS, IL-10, TNF-α, IL-6, and IFN-γ were measured by ELISA. Associations between inflammatory markers and depressive symptoms were examined using group comparisons, correlation analyses, multivariable linear regression, quantile regression, and mediation analyses adjusted for demographic and clinical covariates. Results: Patients with severe depression exhibited significantly lower circulating LPS levels than those with mild-to-moderate depression (95.6 vs. 165.2 pg/mL, p = 0.007), despite no significant differences in cytokine concentrations. LPS levels were inversely associated with depression severity, anhedonia factor score, and MADRS item 8 (“inability to feel”). Lower LPS concentrations were independently predicted by higher inability to feel, reduced appetite and combined pharmacotherapy use. Quantile regression demonstrated heterogeneity across the LPS distribution, with symptom–LPS associations evident among patients with higher LPS concentrations. Higher LPS levels were associated with greater apparent sadness, concentration difficulties, and reduced sleep, but lower levels of anhedonia, less reduced appetite, less lassitude, lower inner tension, and lower suicidality. Mediation analyses indicated that anhedonia mediated the association between LPS levels and depression severity. Conclusions: Higher circulating LPS may characterize a biologically distinct subgroup of MDD patients with lower symptom severity and less anhedonia, supporting biological heterogeneity within MDD.

Objectives: While longitudinal studies have linked parietal lobe structure and muscle mass, no resistance exercise studies have evaluated whether interventions can have a positive impact on parietal lobe structure. Therefore, we investigated the effects of high-intensity resistance training (HIRT) and blood-flow restriction training (BFRT) on cortical thickness and white matter integrity in the parietal region, as well as in other regions, in an exploratory manner. Methods: A total of 63 older men were assigned to BFRT, HIRT or control groups for 12 weeks of intervention. A total of 48 participants completed brain and thigh magnetic resonance imaging before and after intervention. Cortical thickness was assessed using FreeSurfer, fractional anisotropy (FA) values were calculated using ExploreDTI, thigh muscle anatomical cross-sectional area was measured from MRI. Results: A significant difference in cortical thickness was observed only in HIRT group in the left parietal cortex—inferior parietal, supramarginal and posterior cingulate. Exploratory analyses revealed cortical thickness changes in other left-hemisphere regions, including the temporal (bankssts, inferior temporal), frontal (medial orbitofrontal, precentral, rostral middle frontal), and occipital (lateral occipital) cortices. In contrast, the BFRT group showed significant FA value change in parietal region – in left inferior parietal, left precuneus and right superior parietal. Exploratory analyses showed FA value change in additional regions in the BFRT group, including the left frontal (caudal middle frontal and superior frontal), left temporal (fusiform), right occipital (lateral occipital), and in the HIRT group, in the left frontal region (pars opercularis). Conclusions: HIRT and BFRT were associated with beneficial brain structural changes, although through distinct neurobiological mechanisms, with HIRT primarily influencing cortical thickness and BFRT predominantly affecting white matter microstructure.