Sedentary behavior and cognitive impairment have a direct impact on patients’ outcomes. An energy metabolic disorder may be involved in the overlap of these comorbid conditions (motoric cognitive risk (MCR)) in patients with chronic obstructive pulmonary disease (COPD). We aimed to explore the linkage between a proapoptotic protein, growth differentiation factor (GDF)-15, and MCR. Physical activity (PA), cognitive function (Japanese version of the Montreal Cognitive Assessment: MOCA-J), and the serum GDF-15 levels were assessed in healthy subjects (n = 14), asthmatics (n = 22), and COPD patients (n = 28). In the entire cohort, serum GDF-15 had negative correlations with exercise (Ex) (ρ = −0.43, p < 0.001) and MoCA-J (ρ = −0.44, p < 0.001), and Ex and MOCA-J showed a positive correlation (ρ = 0.52, p < 0.0001). Compared to healthy subjects and asthmatics, COPD patients showed the highest serum GDF-15 levels and had a significantly higher proportion of subjects with MCR (both sedentary lifestyle (EX < 1.5) and cognitive risk (MoCA-J ≤ 25)). Also, we found that serum GDF-15 has a screening potential (100% sensitivity) greater than aging (67% sensitivity) for detecting MCR in COPD patients. In conclusion, higher serum GDF-15 had interrelationships with a sedentary lifestyle and cognitive risk. This protein was not disease-specific but could be a screening biomarker to detect MCR related to poor health outcomes of COPD patients.

Introduction: The hippocampus is relevant to cognitive function in schizophrenia (SCZ) and mood disorder patients. Although not anatomically uniform, it is clearly divided into subfields. This study aimed to elucidate the relationship between hippocampal subfield volume and cognitive function in patients with SCZ, bipolar disorder (BP), and major depressive disorder (MDD). Methods: The study included 21 patients with SCZ, 22 with BP, and 21 with MDD and 25 healthy controls (HCs). Neurocognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. We obtained hippocampal subfield volumes using FreeSurfer 6.0. We compared the volumes of the hippocampal subfield between the 4 groups and ascertained correlation between the cognitive composite score and hippocampal subfield volume in each group. Results: The SCZ group had significantly lower cognitive composite score than the BP, MDD, and HC groups. In the SCZ group, the left and right hippocampus-amygdala transition area and right subiculum and right presubiculum volumes were significantly reduced compared to those in the HC group. The left presubiculum volumes in the SCZ group were significantly reduced compared to those in the MDD group. Subfield volumes did not significantly differ between the BP, MDD, and HC groups. Interestingly, in the SCZ group, volumes of the right CA1, right molecular layer of the hippocampus, and right granule cell and molecular layer of the dentate gyrus were significantly correlated with the cognitive composite score. Conclusion: Patients with SCZ had poorer cognitive function, which is related to their hippocampal pathology, than those with mood disorders.

Brain frailty may be related to the pathophysiology of poor clinical outcomes in chronic obstructive pulmonary disease (COPD). This study examines the relationship between hippocampal subfield volumes and frailty and depressive symptoms, and their combined association with quality of life (QOL) in patients with COPD. The study involved 40 patients with COPD. Frailty, depressive symptoms and QOL were assessed using Kihon Checklist (KCL), Hospital Anxiety and Depression Scale (HADS), and World Health Organization Quality of Life Assessment (WHO/QOL-26). Anatomical MRI data were acquired, and volumes of the hippocampal subfields were obtained using FreeSurfer (version 6.0). Statistically, HADS score had significant association with WHO/QOL-26 and KCL scores. KCL scores were significantly associated with volumes of left and right whole hippocampi, presubiculum and subiculum, but HADS score had no significant association with whole hippocampi or hippocampal subfield volumes. Meanwhile, WHO/QOL-26 score was significantly associated with volume of the left CA1. There was a significant association between frailty, depression, and QOL. Hippocampal pathology was related to frailty and, to some extent, with QOL in patients with COPD. Our results suggest the impact of frailty on hippocampal volume and their combined associations with poor QOL in COPD.

Repetitive transcranial magnetic stimulation (rTMS) of the left dorsal prefrontal cortex (DLPFC) has been utilized to manage treatment-resistant major depressive disorder (MDD). Understanding the biological basis of rTMS treatment in MDD is crucial for enhancing its clinical efficacy. Numerous brain regions functionally connected to the left DLPFC have been identified as a critical role in the pathophysiology of MDD, highlighting the significance of alterations in these neural circuits. We employed a dynamic causal modeling to estimate the causal relationships among depression-related regions functionally linked to the left DLPFC using a large-sample, multi-site resting-state functional magnetic resonance imaging dataset, comprising 270 healthy controls and 175 patients with MDD. We revealed aberrant causal connections from the left DLPFC, amygdala (AMY), nucleus accumbens (NAC), and thalamus (Thal) to the visual cortex (VIS) in MDD. We also found negative associations between depression severities and NAC-to-VIS connections, indicating that VIS plays an essential role in MDD. Furthermore, we identified aberrant causal connections between the ventromedial prefrontal cortex (VMPFC) and subcortical regions including, AMY, NAC, and subgenual anterior cingulate cortex (sgACC), and positive correlation between the depression severities and AMY-to-sgACC connection, suggesting the disruption in corticostriatal circuit is related to the aberrant emotional regulation in MDD. These aberrant connections may support the neural mechanisms of MDD and indicate rTMS may modulate these areas, potentially improving the disrupted function in MDD. Our study provides deeper insights into the pathophysiological mechanisms of MDD and the potential mechanisms of rTMS treatment.