Associations between Education Years and Resting-state Functional Connectivity Modulated by APOE ε4 Carrier Status in Cognitively Normal Older Adults

Objective@#Cognitive reserve has emerged as a concept to explain the variable expression of clinical symptoms in the pathology of Alzheimer’s disease (AD). The association between years of education, a proxy of cognitive reserve, and resting-state functional connectivity (rFC), a representative intermediate phenotype, has not been explored in the preclinical phase, considering risk factors for AD. We aimed to evaluate whether the relationship between years of education and rFC in cognitively preserved older adults differs depending on amyloid-beta deposition and APOE ε4 carrier status as effect modifiers. @*Methods@#A total of 121 participants underwent functional magnetic resonance imaging, [ 18F] flutemetamol positron emission tomography-computed tomography, APOE genotyping, and a neuropsychological battery. Potential interactions between years of education and AD risk factors for rFC of AD-vulnerable neural networks were assessed with wholebrain voxel-wise analysis. @*Results@#We found a significant education years-by-APOE ε4 carrier status interaction for the rFC from the seed region of the central executive (CEN) and dorsal attention networks. Moreover, there was a significant interaction of rFC between right superior occipital gyrus and the CEN seed region by APOE ε4 carrier status for memory performances and overall cognitive function. @*Conclusion@#In preclinical APOE ε4 carriers, higher years of education were associated with higher rFC of the AD vulnerable network, but this contributed to lower cognitive function. These results contribute to a deeper understanding of the impact of cognitive reserve on sensitive functional intermediate phenotypic markers in the preclinical phase of AD.

Current Understanding on Psilocybin for Major Depressive Disorder: A Review Focusing on Clinical Trials

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a “breakthrough therapy” for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin’s potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials, DB-RCTs) trials exploring psilocybin’s impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over 6 months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.

Sensory Stimulation-dependent Npas4 Expression in the Olfactory Bulb during Early Postnatal Development

The development of the olfactory system is influenced by sensory inputs, and it maintains neuronal generation and plasticity throughout the lifespan. The olfactory bulb contains a higher proportion of interneurons than other brain regions, particularly during the early postnatal period of neurogenesis. Although the relationship between sensory stimulation and olfactory bulb development during the postnatal period has been well studied, the molecular mechanisms have yet to be identified. In this study, we used western blotting and immunohistochemistry to analyze the expression of the transcription factor Npas4, a neuron-specific immediate-early gene that acts as a developmental regulator in many brain regions.We found that Npas4 is highly expressed in olfactory bulb interneurons during the early postnatal stages and gradually decreases toward the late postnatal stages. Npas4 expression was observed in all olfactory bulb layers, including the rostral migratory stream, where newborn neurons are generated and migrate to the olfactory bulb. Under sensory deprivation, the olfactory bulb size and the number of olfactory bulb interneurons were reduced. Furthermore, Npas4 expression and the expression of putative Npas4 downstream molecules were decreased. Collectively, these findings indicate that Npas4 expression induced by sensory input plays a role in the formation of neural circuits with excitatory mitral/tufted cells by regulating the survival of olfactory bulb interneurons during the early stages of postnatal development.

Development of Efficient Brain Age Estimation Method Based on Regional Brain Volume From Structural Magnetic Resonance Imaging

Objective@#We aimed to create an efficient and valid predicting model which can estimate individuals’ brain age by quantifying their regional brain volumes. @*Methods@#A total of 2,560 structural brain magnetic resonance imaging (MRI) scans, along with demographic and clinical data, were obtained. Pretrained deep-learning models were employed to automatically segment the MRI data, which enabled fast calculation of regional brain volumes. Brain age gaps for each subject were estimated using volumetric values from predefined 12 regions of interest (ROIs): bilateral frontal, parietal, occipital, and temporal lobes, as well as bilateral hippocampus and lateral ventricles. A larger weight was given to the ROIs having a larger mean volumetric difference between the cognitively unimpaired (CU) and cognitively impaired group including mild cognitive impairment (MCI), and dementia groups. The brain age was predicted by adding or subtracting the brain age gap to the chronological age according to the presence or absence of the atrophy region. @*Results@#The study showed significant differences in brain age gaps among CU, MCI, and dementia groups. Furthermore, the brain age gaps exhibited significant correlations with education level and measures of cognitive function, including the clinical dementia rating sum-of-boxes and the Korean version of the Mini-Mental State Examination. @*Conclusion@#The brain age that we developed enabled fast and efficient brain age calculations, and it also reflected individual’s cognitive function and cognitive reserve. Thus, our study suggested that the brain age might be an important marker of brain health that can be used effectively in real clinical settings.

Effects of Serious Games in Older Adults With Mild Cognitive Impairment

Objective@#The rising prevalence of mild cognitive impairment (MCI) has spurred interest in innovative cognitive rehabilitation approaches, including serious games. This review summarizes randomized clinical trials (RCTs) exploring the impact of serious games on MCI patients. @*Methods@#We conducted a comprehensive data search using key terms such as “gamification,” “digital therapy,” “cognition,” “mild cognitive impairment,” and “Alzheimer’s disease.” We exclusively considered published RCTs, excluding animal studies and basic research. @*Results@#We identified eight RCTs. Four RCTs examined the effects of serious games using cognitive training for MCI patients. Notably, one study found that non-specific training (Nintendo Wii) significantly enhanced cognitive function and quality of life compared to cognition-specific computer training (CoTras). Among the remaining three RCTs, one specifically demonstrated that personalized serious game-based cognitive training yielded superior cognitive outcomes and reduced depressive symptoms. One RCT focused on serious games incorporating physical exercise, highlighting the effectiveness of kinetic-based exergaming in enhancing overall cognition. Three RCT focused on combined cognitive training and physical exercise. A double-blind RCT revealed that progressive resistance training or standalone physical exercise outperformed the combined approach in improving executive function and global cognition. Two additional RCTs reported positive outcomes, including improvements in cognitive function and electroencephalogram patterns associated with game-based interventions. @*Conclusion@#Serious games, whether focusing on cognitive training, physical exercise, or a combination of both, have potential to improve cognitive and functional outcomes in individuals with MCI. Further research and standardization of protocols are needed to better understand the full potential of serious games in MCI.

Functional Connectivity Change Associated With Apolipoprotein E Allotypes Precedes Structural Connectivity and Neurodegeneration in Cognitive Normal Older Adults Without Cerebral Aβ Deposition

Objective@#Apolipoprotein E (APOE) gene is known to influence cerebral functional connectivity (FC) in Alzheimer’s disease continuum. We investigated association between APOE allotypes and FC, structural connectivity, and cortical thickness in amyloid-PET negative cognitive normal older adults (CN). @*Methods@#A total of 188 CN (37 had ε2/ε2 or ε2/ε3 [ε2 group], 113 had ε3/ε3 [ε3 group], and 38 had ε3/ε4 or ε4/ε4 [ε4 group]) were recruited. Voxel-based morphometry and cortical thickness analysis were used to investigate differences in cortical thickness between three APOE allotypes. To investigate integrity of structural connectivity, we analyzed diffusion weighted imaging using fractional anisotropy and mean diffusivity. In terms of FC, differences of FC in default mode network (DMN) among APOE allotypes were measured using functional magnetic resonance imaging. @*Results@#There were no significant differences in age, sex, education, cerebral beta-amyloid (Aβ) deposition severity, or neuropsychological profiles. No significant differences were found in cortical thickness and structural connectivity among the APOE allotypes. However, FC within the DMN was significantly lower in ε4 and ε2 carriers compared to ε3 homozygotes. @*Conclusion@#This study suggests that both ε4 and ε2 exhibit APOE-associated DMN FC changes before Aβ deposition, structural changes, and neurodegeneration.

Suicide attempts presenting to the emergency department before and during the COVID-19 pandemic: a comparative study

Objective@#To compare and analyze the differences in the sociodemographic and clinical characteristics of suicide attempters who visited an emergency department (ED) before and during the coronavirus disease (COVID-19) pandemic. @*Methods@#This single center, retrospective study was conducted by reviewing the medical records of patients in the “self-injury/suicide” category of the National Emergency Department Information System who visited an ED between January 2019 and December 2020. We obtained information on baseline characteristics, suicide attempt, and disposition. Data were analyzed using the chi-squared test. @*Results@#A total of 456 patients were included. The number of patients visiting the ED for suicide attempts increased by 18.2% (from 209 to 247 cases) during the COVID-19 pandemic, and the ratio of suicide attempters to the total number of ED visits increased by 48.8% (from 0.43% to 0.64%, P<0.001). There were significant differences in methods of suicide attempt, endotracheal intubation, ED disposition, and the presence of mental illness. Drug overdose (42.1% vs. 53.4%) and gas inhalation (5.7% vs. 8.5%) increased, and hanging decreased (6.0% vs. 2.0%) during the pandemic. Endotracheal intubation (13.9% vs. 5.7%) and intensive care unit admission (29.7% vs. 14.6%) decreased. More patients with the history of mental illness visited during the pandemic (54.0% vs. 70.1%). @*Conclusion@#Since the COVID-19 pandemic began, suicide attempts have increased in this single ED although the lethality of those attempts is low.

Tardive Dystonia Related with Aripiprazole

Tardive dystonia is characterized by sustained, generally slow involuntary twisting movements. It is estimated to occur at a frequency of 1% to 4% among patients who are taking an antipsychotic agent. Unlike the first generation antipsychotics, the second generation antipsychotics are less likely to cause neuroleptic-induced movement disorder. For aripiprazole, only a few cases have been reported for tardive dystonia. We present a young male, who developed a severe tardive dystonia after taking aripiprazole for 5 years. The patient was admitted to for the treatment of both hisdystonic and psychotic symptoms. Olanzapine was administered instead of aripiprazole and while his psychotic symptoms improved, the dystonic symptoms were continued. Therefore, olanzapine was switched to clozapine while augmenting with benzodiazepine, anti-cholinergic, and ginko biloba to control his tardive dystonia. After 2 weeks of treatment, the dystonic movement decreased remarkably.

Effect of Previous Gastrectomy on the Performance of Postoperative Colonoscopy

PURPOSE: The purpose of this study was to determine the effect of a prior gastrectomy on the difficulty of subsequent colonoscopy, and to identify the surgical factors related to difficult colonoscopies. MATERIALS AND METHODS: Patients with a prior gastrectomy who had undergone a colonoscopy between 2011 and 2014 (n=482) were matched (1:6) to patients with no history of gastrectomy (n=2,892). Cecal insertion time, intubation failure, and bowel clearance score were compared between the gastrectomy and control groups, as was a newly generated comprehensive parameter for a difficult/incomplete colonoscopy (cecal intubation failure, cecal insertion time >12.9 minutes, or very poor bowel preparation scale). Surgical factors including surgical approach, extent of gastrectomy, extent of lymph node dissection, and reconstruction type, were analyzed to identify risk factors for colonoscopy performance. RESULTS: A history of gastrectomy was associated with prolonged cecal insertion time (8.7±6.4 vs. 9.7±6.5 minutes; P=0.002), an increased intubation failure rate (0.1% vs. 1.9%; P<0.001), and a poor bowel preparation rate (24.7 vs. 29.0; P=0.047). Age and total gastrectomy (vs. partial gastrectomy) were found to be independent risk factors for increased insertion time, which slowly increased throughout the postoperative duration (0.35 min/yr). Total gastrectomy was the only independent risk factor for the comprehensive parameter of difficult/incomplete colonoscopy. CONCLUSIONS: History of gastrectomy is related to difficult/incomplete colonoscopy performance, especially in cases of total gastrectomy. In any case, it may be that a pre-operative colonoscopy is desirable in selected patients scheduled for gastrectomy; however, it should be performed by an expert endoscopist each time.

The Effect of Glenohumeral Internal Rotation Deficit on the Isokinetic Strength, Pain, and Quality of Life in Male High School Baseball Players

OBJECTIVE: To investigate the effects of glenohumeral internal rotation deficit (GIRD) on the isokinetic strength, body pain, and the quality of life in male high school baseball players of Korea. METHODS: Fifty-six male high school baseball players were divided into either group A (GIRD> or =20degrees, n=12) or group B (GIRD or =20degrees) was 21.43% in the present study. In the isokinetic strength test, a significantly weaker muscular state at an angular velocity of 180degrees/s was observed in group A, compared to group B. For the comparison of the pain, the frequency of shoulder pain was higher (33.93%) than other body pain, among the study subjects. CONCLUSION: GIRD is one of the main risk factors of glenohumeral joint damage, and it is correlated with reduced isokinetic strength and quality of life. High school baseball players will need appropriate shoulder rehabilitation programs for the improvement in their quality of life and performance.

Combined Genome-Wide Linkage and Association Analyses of Fasting Glucose Level in Healthy Twins and Families of Korea

This study was undertaken to identify genetic polymorphisms that are associated with the risk of an elevated fasting glucose (FG) level using genome-wide analyses. We explored a quantitative trait locus (QTL) for FG level in a genome-wide study from a Korean twin-family cohort (the Healthy Twin Study) using a combined linkage and family-based association analysis approach. We investigated 1,754 individuals, which included 432 families and 219 pairs of monozygotic twins. Regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2, were found to show evidence of linkage with FG level, and several markers in these regions were found to be significantly associated with FG level using family-based or general association tests. In particular, a single-nucleotide polymorphism (rs6138953) on the PTPRA gene in the 20p13 region (combined P = 1.8 x 10(-6)) was found to be associated with FG level, and the PRKCB1 gene (in 16p12.1) to be possibly associated with FG level. In conclusion, multiple regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2 are associated with FG level in our Korean twin-family cohort. The combined approach of genome-wide linkage and family-based association analysis is useful to identify novel or known genetic regions concerning FG level in a family cohort study.

Vancomycin-resistant Enterococcus and Methicillin-resistant Staphylococcus aureus Colonization in Liver Transplant Recipients : A Matched Control Study / 대한구급학회지

BACKGROUND: Despite improvements in surgical technique and immunosuppression, infection following liver transplantation (LT) remains a significant problem. Vancomycin-resistant Enterococcuscus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) have become important nosocomial pathogens. This study was undertaken in attempt to evaluate clinical impact of VRE and MRSA in LT recipients. METHODS: LT recipients with VRE or MRSA colonization from 2001 to 2004 were identified and matched (age, gender, United Network for Organ Sharing status, liver disease, and transplant date) to control groups without MRSA or VRE colonization. Demographics, clinical factors, length of stay, duration of the use of the mechanical ventilator, complications and survival rates were compared with matched controls. RESULTS: Eleven patients were colonized by VRE (4.7%) and thirty patients by MRSA (13%). The common sites of VRE culture included the tip of the urinary catheter and urine. The VRE colonized group experienced more biliary complications, relaparotomies, longer length of stay at ICU and ward, and longer use of the mechanical ventilator. One year survival rate was lower in the VRE group. MRSA was commonly cultured from sputum, tip of the central venous catheter or intraarterial catheter, and blood. The MRSA group experienced more relaparotomies, pneumonia, longer stay at ICU and ward, and longer use of mechanical ventilator compared to the control. One year survival rate was lower in the MRSA group. Rejection was not associated with VRE or MRSA infection. CONCLUSIONS: VRE or MRSA colonization is associated with higher incidence of posttransplant complications and lower survival rate than LT recipients without VRE or MRSA colonization. The patients with VRE or MRSA colonization also utilized more hospital resources.