Transcranial direct current stimulation and neuronal functional connectivity in MCI: role of individual factors associated to AD.

Background: Alzheimer's disease (AD) encompasses a spectrum that may progress from mild cognitive impairment (MCI) to full dementia, characterized by amyloid-beta and tau accumulation. Transcranial direct current stimulation (tDCS) is being investigated as a therapeutic option, but its efficacy in relation to individual genetic and biological risk factors remains underexplored. Objective: To evaluate the effects of a two-week anodal tDCS regimen on the left dorsolateral prefrontal cortex, focusing on functional connectivity changes in neural networks in MCI patients resulting from various possible underlying disorders, considering individual factors associated to AD such as amyloid-beta deposition, APOE ϵ4 allele, BDNF Val66Met polymorphism, and sex. Methods: In a single-arm prospective study, 63 patients with MCI, including both amyloid-PET positive and negative cases, received 10 sessions of tDCS. We assessed intra- and inter-network functional connectivity (FC) using fMRI and analyzed interactions between tDCS effects and individual factors associated to AD. Results: tDCS significantly enhanced intra-network FC within the Salience Network (SN) and inter-network FC between the Central Executive Network and SN, predominantly in APOE ϵ4 carriers. We also observed significant sex*tDCS interactions that benefited inter-network FC among females. Furthermore, the effects of multiple modifiers, particularly the interaction of the BDNF Val66Met polymorphism and sex, were evident, as demonstrated by increased intra-network FC of the SN in female Met non-carriers. Lastly, the effects of tDCS on FC did not differ between the group of 26 MCI patients with cerebral amyloid-beta deposition detected by flutemetamol PET and the group of 37 MCI patients without cerebral amyloid-beta deposition. Conclusions: The study highlights the importance of precision medicine in tDCS applications for MCI, suggesting that individual genetic and biological profiles significantly influence therapeutic outcomes. Tailoring interventions based on these profiles may optimize treatment efficacy in early stages of AD.

Impact of multiple infections on risk of incident dementia according to subjective cognitive decline status: a nationwide population-based cohort study.

Background: The interrelation between infections, subjective cognitive decline (SCD), and dementia development is recognized, but not fully understood. This study explored the combined effect of specific infections and SCD on the risk of dementia. Objectives: To assess the influence of Helicobacter pylori, herpes simplex virus, varicella-zoster virus, and human papillomavirus on dementia risk in individuals with varying cognitive statuses, especially focusing on those with and without SCD. Methods: A cohort of 1,100,540 participants aged 66 years from the Korean National Health Insurance Service was divided into cognitively preserved (CP, n = 825,405) and SCD (n = 275,135) groups. This study analyzed the effects of single, dual, and triple infections on the risk of overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD) using incidence rates and hazard ratios. Results: The SCD group consistently showed a doubled risk of dementia, particularly AD, regardless of the number of infections. In the initial data, both the presence and number of infections, especially in the CP group, were associated with an increased dementia incidence and risk; however, this correlation disappeared after adjusting for covariates, hinting at a possible protective effect. Conclusion: Our findings emphasize that, while SCD is a steadfast risk factor for dementia, the role of infections is layered, subject to various influences, and requires more comprehensive exploration to fully understand their impact on dementia development.

Sphingolipid metabolites as potential circulating biomarkers for sarcopenia in men.

BACKGROUND: Sarcopenia is an age-related progressive loss of muscle mass and function. Sarcopenia is a multifactorial disorder, including metabolic disturbance; therefore, metabolites may be used as circulating biomarkers for sarcopenia. We aimed to investigate potential biomarkers of sarcopenia using metabolomics. METHODS: After non-targeted metabolome profiling of plasma from mice of an aging mouse model of sarcopenia, sphingolipid metabolites and muscle cells from the animal model were evaluated using targeted metabolome profiling. The associations between sphingolipid metabolites identified from mouse and cell studies and sarcopenia status were assessed in men in an age-matched discovery (72 cases and 72 controls) and validation (36 cases and 128 controls) cohort; women with sarcopenia (36 cases and 36 controls) were also included as a discovery cohort. RESULTS: Both non-targeted and targeted metabolome profiling in the experimental studies showed an association between sphingolipid metabolites, including ceramides (CERs) and sphingomyelins (SMs), and sarcopenia. Plasma SM (16:0), CER (24:1), and SM (24:1) levels in men with sarcopenia were significantly higher in the discovery cohort than in the controls (all P < 0.05). There were no significant differences in plasma sphingolipid levels for women with or without sarcopenia. In men in the discovery cohort, an area under the receiver-operating characteristic curve (AUROC) of SM (16:0) for low muscle strength and low muscle mass was 0.600 (95% confidence interval [CI]: 0.501-0.699) and 0.647 (95% CI: 0.557-0.737). The AUROC (95% CI) of CER (24:1) and SM (24:1) for low muscle mass in men was 0.669 (95% CI: 0.581-0.757) and 0.670 (95% CI: 0.582-0.759), respectively. Using a regression equation combining CER (24:1) and SM (16:0) levels, a sphingolipid (SphL) score was calculated; an AUROC of the SphL score for sarcopenia was 0.712 (95% CI: 0.626-0.798). The addition of the SphL score to HGS significantly improved the AUC from 0.646 (95% CI: 0.575-0.717; HGS only) to 0.751 (95% CI: 0.671-0.831, P = 0.002; HGS + SphL) in the discovery cohort. The predictive ability of the SphL score for sarcopenia was confirmed in the validation cohort (AUROC = 0.695, 95% CI: 0.591-0.799). CONCLUSIONS: SM (16:0), reflecting low muscle strength, and CER (24:1) and SM (16:0), reflecting low muscle mass, are potential circulating biomarkers for sarcopenia in men. Further research on sphingolipid metabolites is required to confirm these results and provide additional insights into the metabolomic changes relevant to the pathogenesis and diagnosis of sarcopenia.

Obstructive Sleep Apnea and Medical Comorbidities in the Asian Population: Evidence From a Nationwide Healthcare System Data in South Korea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a breathing disorder characterized by recurrent airway obstruction during sleep. Previous western studies have investigated the link between medical disorders and the pathophysiology of OSA. The prevalence and comorbidity rates of OSA; however, vary across different countries and racial groups. This study aimed to delve into medical comorbidities in patients with OSA using a large nationwide healthcare database in Korea. METHODS: This nationwide study used the Korean National Health Insurance claims database (2010-2019). The effect of OSA on the incidence of medical disorders was estimated using the Cox proportional hazard ratio (HR) model. The results were reported as crude and adjusted HRs with 95% confidence intervals (CI). Subgroup analysis was conducted by sex and age. RESULTS: In total, 103,785 patients with OSA and 207,570 patients without OSA were included. OSA group had significantly higher HRs for ischemic heart disease and stroke even after adjusting for hypertension, dyslipidemia, and diabetes. The OSA group also showed an increased risk of metabolic syndrome-related diseases, chronic kidney disease, and gastroesophageal reflux disease. Female patients with OSA exhibited notably higher rates of comorbid liver cirrhosis, chronic obstructive pulmonary disease, and asthma. The cardiovascular burden of patients increased in accordance with the patients' age. CONCLUSION: Korean patients with OSA have a significantly increased risk of cardio-cerebrovascular diseases, which aligns with the previous studies conducted in the western countries. This result holds particular significance as it represents the first nationwide, population-based study conducted in Asia.

Effects of transcranial direct current stimulation on cognition in MCI with Alzheimer's disease risk factors using Bayesian analysis.

Despite the growing interest in precision medicine-based therapies for Alzheimer's disease (AD), little research has been conducted on how individual AD risk factors influence changes in cognitive function following transcranial direct current stimulation (tDCS). This study evaluates the cognitive effects of sequential tDCS on 63 mild cognitive impairment (MCI) patients, considering AD risk factors such as amyloid-beta deposition, APOE ε4, BDNF polymorphism, and sex. Using both frequentist and Bayesian methods, we assessed the interaction of tDCS with these risk factors on cognitive performance. Notably, we found that amyloid-beta deposition significantly interacted with tDCS in improving executive function, specifically Stroop Word-Color scores, with strong Bayesian support for this finding. Memory enhancements were differentially influenced by BDNF Met carrier status. However, sex and APOE ε4 status did not show significant effects. Our results highlight the importance of individual AD risk factors in modulating cognitive outcomes from tDCS, suggesting that precision medicine may offer more effective tDCS treatments tailored to individual risk profiles in early AD stages.

Impact of Helicobacter pylori eradication on age-specific risk of incident dementia in patients with peptic ulcer disease: a nationwide population-based cohort study.

The impact of peptic ulcer disease (PUD) and Helicobacter pylori (H. pylori) eradication therapy on dementia risk in high H. pylori prevalence populations remains uncertain. This study investigates the relationship between PUD, H. pylori eradication, and dementia risk, including Alzheimer's disease (AD), in an elderly South Korean cohort, considering age and eradication timing. Data from the Korean National Health Insurance Service (2002-2015) for individuals aged 55-79 were analyzed. Participants were divided based on PUD and H. pylori therapy status. Propensity score matching was used to evaluate dementia incidence and hazard ratios over 5 and 10 years, alongside the timing of eradication therapy. PUD is linked to higher dementia risk at 5 and 10 years, more for overall dementia than AD, with eradication status not significantly altering the risk. Age-specific analysis showed increased AD risk in the 60s and 70s age groups. Late eradication therapy is correlated with a higher dementia risk. PUD is a risk factor for dementia in elderly South Koreans, particularly with delayed H. pylori therapy. The findings emphasize timely H. pylori management and its potential role in neurodegenerative disease prevention.

Effects of high tibial osteotomy on the coronal, sagittal, and axial alignments of the ankle joint.

BACKGROUND: No comprehensive study has been conducted on the effects of high tibial osteotomy (HTO) on the coronal, sagittal, and axial alignments of the ankle joint. Therefore, this study aimed to investigate the multiplane changes in the ankle joint following HTO using the EOS biplanar X-ray imaging system. METHODS: The medical records of 43 patients who underwent HTO for the treatment of medial knee osteoarthritis were retrospectively reviewed. Preoperative and postoperative EOS images and lower-extremity scanograms were evaluated; the correlations between the outcomes were evaluated. RESULTS: After HTO, the ankle joint axis point on the weight-bearing line showed significant lateralization (p < .001). The knee lateral ankle surface angle increased significantly in the sagittal alignment (p < .001). The distal tibia showed a significant internal rotation in the axial plane (p = .022). Tibial rotation showed no significant relationship with the other parameters. CONCLUSIONS: HTO induced lateralization of the ankle joint axis (coronal), increased the posterior tibial slope (sagittal), and caused the internal rotation of the distal tibia (axial). Axial changes in the distal tibia showed no significant relationship with other coronal and sagittal parameters of the ankle joint. We suggest that surgeons should consider, during HTO, that the ankle joint axis shifts laterally and distal tibia has tendency to rotate internally after HTO.

A Comparative Analysis of Two Automated Quantification Methods for Regional Cerebral Amyloid Retention: PET-Only and PET-and-MRI-Based Methods.

Accurate quantification of amyloid positron emission tomography (PET) is essential for early detection of and intervention in Alzheimer's disease (AD) but there is still a lack of studies comparing the performance of various automated methods. This study compared the PET-only method and PET-and-MRI-based method with a pre-trained deep learning segmentation model. A large sample of 1180 participants in the Catholic Aging Brain Imaging (CABI) database was analyzed to calculate the regional standardized uptake value ratio (SUVR) using both methods. The logistic regression models were employed to assess the discriminability of amyloid-positive and negative groups through 10-fold cross-validation and area under the receiver operating characteristics (AUROC) metrics. The two methods showed a high correlation in calculating SUVRs but the PET-MRI method, incorporating MRI data for anatomical accuracy, demonstrated superior performance in predicting amyloid-positivity. The parietal, frontal, and cingulate importantly contributed to the prediction. The PET-MRI method with a pre-trained deep learning model approach provides an efficient and precise method for earlier diagnosis and intervention in the AD continuum.

Introduction to the Forensic Research via Omics Markers in Environmental Health Vulnerable Areas (FROM) study.

This research group (FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas­including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter­along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.

Differences in Electroencephalography Power and Asymmetry at Frontal Region in Young Adults with Attention-deficit/hyperactivity Disorder: A Quantitative Electroencephalography Study.

Objective: : Diagnosing attention-deficit/hyperactivity disorder (ADHD) in adults is often hard. This study aimed to determine differences in absolute EEG power and frontal asymmetry between individuals with ADHD and non-ADHD in young adults aged 18-30 years. Methods: : Young adult (age: 18-30 years) outpatients (n = 103) including ADHD patients (n = 51) and non-ADHD patients (n = 52) were enrolled. QEEG was performed for both groups for each region of the brain. The absolute power of each frequency measured in three frontal regions (Lt., Mid., Rt.) of the scalp area was compared between the two groups. Differences between the two groups including theta/beta ratio were compared. Frontal asymmetries were also evaluated for prefrontal (Fp2-Fp1), middle frontal (F4-F3), lateral frontal (F8-F7) pairs at all frequencies. Correlation analysis was performed for absolute powers, frontal asymmetry, and Stroop tests. Results: : Demographic data, neuropsychological tests, and psychiatric symptoms were not significantly different between the two groups. Delta band was significantly increased while beta band was decreased in the middle frontal area of the ADHD group as compared with those of the non-ADHD group. For frontal asymmetries, all frequencies in the middle frontal area were more rightward in ADHD patients than in non-ADHD patients. Absolute powers in delta, beta band, and frontal asymmetry in all frequencies had correlations with Stroop tests. Conclusion: : This study revealed that ADHD patients had significant differences in absolute powers in delta, beta bands, and frontal asymmetries in all frequencies. Our findings suggest that QEEG can be a helpful tool for diagnosing ADHD in psychiatric patients.

Improvement in Testosterone Production by Acorus gramineus for the Alleviation of Andropause Symptoms.

Acorus gramineus has a number of beneficial effects, including protective effects against age-related disorders. In this study, the effects of A. gramineus on testosterone production and andropause symptoms were evaluated. We first treated TM3 mouse Leydig cells, responsible for testosterone production, with A. gramineus aqueous extract at different concentrations. In TM3 cells, the testosterone concentration increased in a concentration-dependent manner compared with those in the control. In addition, at 400 µg/mL extract, the mRNA expression level of the steroidogenic enzyme CYP11A1 was increased. Subsequently, 23-week-old Sprague-Dawley (SD) rats exhibiting an age-related reduction in serum testosterone (approximately 80% lower than that in 7-week-old SD rats) were administered A. gramineus aqueous extract for 8 weeks. Serum total testosterone and free testosterone levels were higher and serum estradiol, prostate-specific antigen levels, and total cholesterol levels were lower in the AG50 group (A. gramineus aqueous extract 50 mg/kg of body weight/day) than in the OLD (control group). The AG50 group also showed significant elevations in sperm count, grip strength, and mRNA expression of StAR, CYP11A1, 17ß-HSD, and CYP17A1 compared with those in the OLD group. In conclusion, A. gramineus aqueous extract facilitated steroidogenesis in Leydig cells, elevated testosterone levels, lowered serum estradiol and total cholesterol levels, and increased muscle strength and sperm count, thus alleviating the symptoms of andropause. These findings suggest that A. gramineus aqueous extract is a potentially effective therapeutic agent against various symptoms associated with andropause.

Development of a prediction model for cognitive impairment of sarcopenia using multimodal neuroimaging in non-demented older adults.

INTRODUCTION: Despite prior research on the association between sarcopenia and cognitive impairment in the elderly, a comprehensive model that integrates various brain pathologies is still lacking. METHODS: We used data from 528 non-demented older adults with or without sarcopenia in the Catholic Aging Brain Imaging (CABI) database, containing magnetic resonance imaging scans, positron emission tomography scans, and clinical data. We also measured three key components of sarcopenia: skeletal muscle index (SMI), hand grip strength (HGS), and the five times sit-to-stand test (5STS). RESULTS: All components of sarcopenia were significantly correlated with global cognitive function, but cortical thickness and amyloid-beta (Aß) retention had distinctive relationships with each measure. In the path model, brain atrophy resulting in cognitive impairment was mediated by Aß retention for SMI and periventricular white matter hyperintensity for HGS, but directly affected by the 5STS. DISCUSSION: Treatments targeting each sub-domain of sarcopenia should be considered to prevent cognitive decline. HIGHLIGHTS: We identified distinct impacts of three sarcopenia measures on brain structure and Aß. Muscle mass is mainly associated with Aß and has an influence on the brain atrophy. Muscle strength linked with periventricular WMH and brain atrophy. Muscle function associated with cortical thinning in specific brain regions. Interventions on sarcopenia may be important to ease cognitive decline in the elderly.

Prediction of gait recovery using machine learning algorithms in patients with spinal cord injury.

With advances in artificial intelligence, machine learning (ML) has been widely applied to predict functional outcomes in clinical medicine. However, there has been no attempt to predict walking ability after spinal cord injury (SCI) based on ML. In this situation, the main purpose of this study was to predict gait recovery after SCI at discharge from an acute rehabilitation facility using various ML algorithms. In addition, we explored important variables that were related to the prognosis. Finally, we attempted to suggest an ML-based decision support system (DSS) for predicting gait recovery after SCI. Data were collected retrospectively from patients with SCI admitted to an acute rehabilitation facility between June 2008 to December 2021. Linear regression analysis and ML algorithms (random forest [RF], decision tree [DT], and support vector machine) were used to predict the functional ambulation category at the time of discharge (FAC_DC) in patients with traumatic or non-traumatic SCI (n = 353). The independent variables were age, sex, duration of acute care and rehabilitation, comorbidities, neurological information entered into the International Standards for Neurological Classification of SCI worksheet, and somatosensory-evoked potentials at the time of admission to the acute rehabilitation facility. In addition, the importance of variables and DT-based DSS for FAC_DC was analyzed. As a result, RF and DT accurately predicted the FAC_DC measured by the root mean squared error. The root mean squared error of RF and the DT were 1.09 and 1.24 for all participants, 1.20 and 1.06 for those with trauma, and 1.12 and 1.03 for those with non-trauma, respectively. In the analysis of important variables, the initial FAC was found to be the most influential factor in all groups. In addition, we could provide a simple DSS based on strong predictors such as the initial FAC, American Spinal Injury Association Impairment Scale grades, and neurological level of injury. In conclusion, we provide that ML can accurately predict gait recovery after SCI for the first time. By focusing on important variables and DSS, we can guide early prognosis and establish personalized rehabilitation strategies in acute rehabilitation hospitals.

The complete mitochondrial genome of Membranipora villosa Hincks, 1880 (Bryozoa: Gymnolaemata: Cheilostomatida): phylogenetic relationship of two kelp-encrusting bryozoans within the suborder Membraniporina.

The two commonest kelp-encrusting bryozoans, Membranipora villosa and M. membranacea, are difficult to distinguish morphologically. Molecular studies of M. villosa should thus be helpful for the identification of both species because the mitogenome of M. membranacea was already sequenced. The complete mitogenome of M. villosa collected from Sinjido was determined in this study through Illumina NovaSeq sequencing. Maximum-likelihood (ML) analysis was based on concatenated 13 protein-coding genes dataset from nine bryozoan species. The mitogenome length was 15,407 bp, and its gene arrangement was similar to those of the mitogenome of other membraniporids, having 13 PCGs, two ribosomal RNAs, and 22 tRNAs. It had an overall A + T content of 63.7% (29.7% A, 16.7% C, 19.6% G, and 34.0% T). M. villosa and M. membranacea showed sequence differences of 20% for the total length of mitogenome and 16.1.% for 13 PCGs. Molecular data definitely consider them to be separate species. Phylogenetic analyses based on the amino acids of 13 PCGs indicated that M. villosa has the closest relationship with another kelp-encrusting bryozoan, M. membranacea of membraniporids. The phylogenetic position of genera and families within the suborder Membraniporina coincides with the Bayesian phylogenetic analysis of the mixed concatenated alignment consisting of three partitions.

Clinical Relevance of Posterior Osteophyte Formation in Ultra-congruent Total Knee Arthroplasty: Midterm Radiographic Rollback and Impingement Analysis.

Background: Posterior femoral condylar osteophytes were frequently observed in patients with the ultra-congruent (UC) deep-dish design prosthesis. Therefore, the purpose of the present study was to verify the clinical relevance of osteophyte formation in the UC design. Methods: From March 2014 to February 2018, a comparative study was conducted on 96 knees using the UC design. They were divided into 2 groups (group 1: osteophyte +, group 2: osteophyte -). Intraoperative findings, indirect femoral rollback assessment using 30° flexion and active full flexion lateral radiographs, serial change of the osteophyte, and outcomes were compared. Results: The mean follow-up period was 49.35 ± 3.47 months in group 1 and 47.52 ± 3.37 months in group 2. Posterior component coverage was significantly different between the groups: group 1 exhibited more underhang and group 2 exhibited more overhang (p = 0.022). On the indirect assessment of the femoral rollback, there was a statistically significant difference in deep flexion and change in distance (p < 0.001 and p < 0.001, respectively). There was no statistical difference between the 2 groups in the American Knee Society knee and function score, and group 2 showed significant improvement in pain compared to group 1 in Western Ontario and McMaster University Arthritis Index pain score (p = 0.029). Conclusions: Posterior condylar osteophyte formation was related to posterior impingement. It was more frequently observed in the underhang of the femoral component and insufficient femoral rollback. In addition, it changed with time and caused negative effects, including a gradual decrease in flexion and more pain.

Metabolomic pathways in food allergy.

Food allergy (FA) is a widespread issue, affecting as many as 10% of the population. Over the past two to three decades, the prevalence of FA has been on the rise, particularly in industrialized and westernized countries. FA is a complex, multifactorial disease mediated by type 2 immune responses and involving environmental and genetic factors. However, the precise mechanisms remain inadequately understood. Metabolomics has the potential to identify disease endotypes, which could beneficially promote personalized prevention and treatment. A metabolome approach would facilitate the identification of surrogate metabolite markers reflecting the disease activity and prognosis. Here, we present a literature overview of recent metabolomic studies conducted on children with FA.

Association Between Hypnotics and Dementia: A Mini Narrative Review.

OBJECTIVE: This narrative review aims to provide a comprehensive assessment of the existing literature on the relationship between hypnotics and dementia, considering both potential link and inconclusive or lack of association. METHODS: Data from studies that investigate the association between hypnotic medications and dementia were reviewed. Studies included both cohort studies and systematic reviews, participants with various type of dementia and hypnotics including benzodiazepines (BZDs) and Z-drugs (ZDs). RESULTS: The existing literatures presents conflicting evidence regarding the association between hypnotics, including BZDs and ZDs, and the risk of dementia. Some studies suggest a potential link between prolonged use of hypnotics and an increased risk of dementia. However, other studies indicate inconclusive or lacking evidence regarding this association. Factors such as study design, sample characteristics, and control of confounding variables contribute to the variability in findings. CONCLUSION: The relationship between hypnotics and dementia remains complex and controversial. While some studies suggest a potential association, others find inconclusive or conflicting evidence. Future research should focus on addressing methodological limitations, considering classifying dementia subtypes, and try to adjust medication lag time.

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.

Associations between plasma metabolites and heavy metal exposure in residents of environmentally polluted areas.

Heavy metals are commonly released into the environment through industrial processes such as mining and refining. The rapid industrialization that occurred in South Korea during the 1960s and 1970s contributed significantly to the economy of the country; however, the associated mining and refining led to considerable environmental pollution, and although mining is now in decline in South Korea, the detrimental effects on residents inhabiting the surrounding areas remain. The bioaccumulation of toxic heavy metals leads to metabolic alterations in human homeostasis, with disruptions in this balance leading to various health issues. This study used metabolomics to explore metabolomic alterations in the plasma samples of residents living in mining and refining areas. The results showed significant increases in metabolites involved in glycolysis and the surrounding metabolic pathways, such as glucose-6-phosphate, phosphoenolpyruvate, lactate, and inosine monophosphate, in those inhabiting polluted areas. An investigation of the associations between metabolites and blood clinical parameters through meet-in-the-middle analysis indicated that female residents were more affected by heavy metal exposure, resulting in more metabolomic alterations. For women, inhabiting the abandoned mine area, metabolites in the glycolysis and pentose phosphate pathways, such as ribose-5-phosphate and 3-phosphoglycerate, have shown a negative correlation with albumin and calcium. Finally, Mendelian randomization(MR) was used to determine the causal effects of these heavy metal exposure-related metabolites on heavy metal exposure-related clinical parameters. Metabolite biomarkers could provide insights into altered metabolic pathways related to exposure to toxic heavy metals and improve our understanding of the molecular mechanisms underlying the health effects of toxic heavy metal exposure.