ObjectiveAge-related cognitive decline (ARCD) is highly prevalent in aging populations and is characterized by progressive declines in cognitive function—particularly executive function (EF), which merits focused investigation. This study aimed to compare prefrontal cortex (PFC) activation patterns between ARCD patients with executive dysfunction (ED) and those with non-executive dysfunction (non-ED) using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task (VFT). It further explored correlations between alterations in PFC activation, the severity of EF impairment, and global cognitive function.MethodsA total of 36 elderly individuals diagnosed with ARCD were recruited for this study. Participants were stratified into the ED group or the non-ED group based on neuropsychological test performance, with 18 individuals in each group. fNIRS was employed during the VFT to assess cortical activity. Additionally, a comprehensive neuropsychological assessment was conducted to evaluate global cognitive function, as well as specific domains related to memory and EF. Correlations between PFC activation, as reflected by changes in oxyhemoglobin (oxy-Hb) concentration and cognitive outcomes were analyzed.ResultsThe participants of the ED group were older than those in the non-ED group, and had a higher incidence of type 2 diabetes mellitus than those in the non-ED group. The fNIRS-VFT analysis revealed no activation of the PFC in the ED group (p > 0.05), whereas only minimal activation of the left frontal pole was observed in the non-ED group of ARCD (FDR-corrected p < 0.05). Specifically, activation at Channel 13 (located at the left frontal pole) was statistically higher in the non-ED group than in the ED group at the uncorrected level (p < 0.05); however, this difference became non-significant after FDR correction (p > 0.05). Additionally, the Montreal Cognitive Assessment (MoCA) score was significantly correlated with oxy-Hb concentration changes at Channel 21 (located at the left frontal pole, rs = 0.515, FDR-corrected p < 0.05).ConclusionARCD showed attenuated PFC activation during VFT, with no significant difference between the ED and non-ED groups. The decline in PFC activation was correlated with lower MoCA scores, suggesting that fNIRS-derived PFC activation metrics might serve as a potential biomarker for global cognitive decline in ARCD.

Abstract The rising prevalence of Mild Cognitive Impairment (MCI) demands effective early interventions to delay progression to dementia. This randomized controlled trial evaluated the effects of remote cognitive-motor dual-task training on cognitive function and brain functional connectivity in older adults with MCI. Linear mixed-effects models (subjects as random effects; group, time, and their interaction as fixed effects) revealed significant Group × Time interactions for MoCA scores, Mini-Mental State Examination (MMSE) scores, and brain functional connectivity (FC) (all P < 0.001), indicating that intervention effects differed across groups over time. Post-hoc comparisons showed that the Remote Cognitive-Motor Group (RCMG) achieved significant improvements in both MoCA and MMSE scores (both P < 0.001), and these gains significantly exceeded those of the Control Group (CG) ( P < 0.001). The Remote Cognitive Group (RCG) showed a significant improvement in MoCA ( P < 0.001), whereas no significant improvement was observed in MMSE ( P = 0.188). For brain FC, the RCMG showed significantly greater post-intervention enhancement than the CG ( P < 0.001). Although the RCG showed a nominally significant interaction effect ( P = 0.016), this did not remain significant after correction for multiple comparisons, and no significant difference was observed between RCMG and RCG. Region-of-interest (ROI) analyses revealed that the RCMG exhibited significantly enhanced FC between multiple prefrontal and motor-related regions, including the mPFC, DLPFC, and PMC ( P < 0.05). Trial registration Study on rehabilitation training of cognitive-motor dual tasks for aging-related cognitive decline (ChiCTR2200064684) and the registration date was 10/14/2022.

BackgroundWearable lower-limb exoskeletons have the potential to support intention-driven control of lower-limb exoskeletons, but existing control strategies often rely on mechanical or manual triggers that fail to capture user intent.MethodSubjects were recruited from 23/9/2024 to 10/2/2025. A BiLSTM detector was pretrained on a dataset collected from 50 healthy volunteers (45 for training, 5 for independent testing) using bilateral surface EMG recordings from six lower-limb muscles (12 EMG channels), 16-channel EEG, and hip–knee kinematics. Seven naive participants then completed ten 20-m outward-and-return walking trials (10 m outward and 10 m return) under each of three control modes (EMG, EEG, hybrid). Primary outcomes were triggering latency and classification accuracy. Triggering latency was defined as the time interval between the onset of the gait-transition event and the activation of the exoskeleton assistance command. This latency included the observation delay introduced by the sliding window, feature extraction time, BiLSTM inference time, and communication delay between the decoder and the exoskeleton controller. Usability was assessed with donning/doffing times and QUEST 2.0.ResultsThe hybrid BiLSTM detector achieved higher classification accuracy (left: 91.3%; right: 86.6%) and shorter mean per-step triggering latency (left: 0.29 s; right: 0.28 s) than either EMG-only (mean 0.33 s) or EEG-only approaches (mean 0.30 s). Hybrid EEG–EMG fusion therefore improved decoding performance while reducing triggering latency compared with unimodal decoding strategies. The latency reduction relative to EMG-only control corresponded to a large effect size (Cohen’s d ≈ 0.88). Hybrid sessions also yielded shorter total session time (mean 32.1 min). Usability metrics demonstrated acceptable donning/doffing times and favorable QUEST 2.0 scores (mean 32.0/40).ConclusionThese proof-of-concept results demonstrate that BiLSTM-based fusion of EEG and EMG improves responsiveness and classification reliability for exoskeleton assistance. These findings underscore the contribution of EEG-derived sensorimotor features and EMG information for intention-related gait transition detection within a multimodal real-time exoskeleton control framework. We discuss limitations related to sample size, artifact validation, and generalizability and identify next steps for patient studies and ergonomic optimization.

Cognitive–exercise dual-task training has been shown to enhance cognitive function through mechanisms such as suppression of chronic inflammation, reduction of oxidative stress, and enhancement of synaptic plasticity. However, the precise mechanisms underlying the ability of dual-task training to delay aging-related cognitive decline remain incompletely understood. Aged male C57BL/6J mice were subjected to a 12-week intervention program consisting of cognitive training, exercise, or cognitive–exercise dual-task training. Cognitive and physical function were assessed using a battery of behavioral tests, including the open field test, elevated plus maze test, inverted grid test, wire hanging test, rotarod test, novel object recognition test, novel object localization test, eight-arm maze test, and Morris water maze test. Hippocampal aging and associated molecular changes were assessed using multiple techniques, including terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, Nissl staining, immunohistochemistry, immunofluorescence, flow cytometry, quantitative polymerase chain reaction, Western blotting, co-immunoprecipitation, and dual-luciferase reporter assays. In addition, we established in vitro models of cellular senescence using d-galactose, RNA overexpression/silencing models utilizing siRNA, and Ephrin type-B receptor 2 (EphB2) inducer/inhibitor models to explore specific molecular mechanisms. Age-related upregulation in microRNA (miR)-204 and downregulation in long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) were observed to disrupt Ephrin-B1 (EFNB1)/EphB2 interactions, leading to reduced cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway activation. These alterations were implicated in the pathogenesis of aging-related cognitive decline. Timely interventions, especially cognitive–exercise dual-task, were found to attenuate these phenomena, thereby delaying the progression of aging-related cognitive decline. Timely intervention during the aging process can effectively delay the progression of cognitive decline. The effects of cognitive–exercise dual-task training may surpass those of single-task interventions with either cognitive training or exercise alone.

The study investigated the effectiveness of combining aerobic exercise (AE) with varying durations of cognitive training (CT) to improve age-related cognitive impairment. In a randomized controlled trial with 84 participants, they were assigned to one of four groups: 30-min AE + 30-min CT, 30-min AE + 15-min CT, AE-only, or a control group. Over 12 weeks, participants performed moderate-intensity aerobic exercise three times per week, with cognitive training durations of 30, 15, or 0 min. Significant improvements in cognitive function (MoCA scores) were observed in all exercise groups, with the 30-min AE + 30-min CT group showing the most pronounced benefits. This group also showed improvements in physical and mental quality of life (SF-36). No significant changes were noted in the MMSE or activities of daily living (Lawton-IADL scale). The findings suggest that combining aerobic exercise with 30-minute cognitive training improves cognitive function and quality of life in older adults.

The metabolites produced by the gut microbiota play a role in age-related cognitive decline through the gut-brain axis. Within this axis, trimethylamine N-oxide (TMAO) permeates the intestinal epithelial barrier and enters systemic circulation, triggering inflammation in the central nervous system and ultimately leading to cognitive decline. However, it remains unclear whether exercise training’s specific mechanism for delaying age-related cognitive decline is associated with TMAO regulation and inhibition of neuroinflammation. The aging rat model was established by intraperitoneal injection of D-galactose in SD rats, while simultaneous exercise training and TMAO interventions were conducted. The effects of exercise on cognitive function were evaluated using the new object recognition (NOR) test, the Morris water maze (MWM) test, and the radial arm maze (RAM) test. Additionally, the expression levels of TMAO and NLRP3 inflammasome-related proteins in aging rats were measured using enzyme-linked immunosorbent assays (ELISA) and Western blotting (WB), respectively. A D-galactose-induced senescence model was established in HT22 cells. Following TMAO/DMB intervention, SPiDER-β-galactosidase (SPiDER-β-gal)-positive cells and NLRP3 inflammasome-related proteins were analyzed. To validate the regulatory role of TXNIP in TMAO-induced senescence-inflammation phenotypes, knockdown/overexpression experiments were conducted. Trx1-C32S mutant cells were utilized to verify that TMAO enhances the disulfide bond binding affinity between TXNIP and Trx1. Exercise training effectively delayed the cognitive dysfunction induced by D-galactose in aging rats, as evidenced by a 22.6% increase in the discrimination index in the NOR test, an 11.2% prolongation of time in the target quadrant and a 50% enhancement in the number of platform crossings in the MWM test, and a 41.8% improvement in working memory in the RAM test. This neuroprotective effect is potentially mediated through the inhibition of the intestinal metabolite TMAO (with plasma TMAO levels reduced by 40.3%) and subsequent modulation of the TXNIP-NLRP3-Caspase-1-GSDMD inflammatory pathway. The cellular experiments revealed that TMAO/DMB intervention modulates cellular senescence-inflammation phenotypes, with TXNIP acting as a positive regulator of the NLRP3 pathway. TMAO enhances TXNIP-mediated inhibition of the redox system by promoting disulfide bond formation at Trx1-C32, providing cellular-level evidence for the underlying mechanism.

With the acceleration of population aging, cognitive dysfunction-related diseases have emerged as significant public health questions to the health of China's elderly population. There is an urgent clinical need to expedite the development of an evidence-based and accessible non-pharmacological intervention system for cognitive dysfunction. The consensus encompasses neuromodulation techniques [transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS)], exercise interventions (aerobic exercise, resistance training, combined aerobic-resistance training, and integrated task-based interventions), cognitive training (conventional paper-and-pencil training, computer-assisted cognitive training, and tailored training), dietary interventions (Mediterranean diet, ketogenic diet, and dietary approaches to stop hypertension), psychosocial therapies (psychotherapy, music and movement therapy, calligraphy training, music therapy, animal-assisted therapy, doll therapy, and reminiscence therapy), and traditional Chinese medicine therapies (acupuncture, tuina massage, and Qigong) as non-pharmacological interventions for cognitive dysfunction. It aims to enhance the recognition and attention to non-pharmacological treatment of cognitive dysfunction in medical and management institutions at all levels, providing patients with more diverse and effective therapeutic options as well as standardized management.

We aim to investigate the changes in brain functional connectivity induced by cognitive fatigue from a whole-brain perspective and multiple angles to uncover the underlying mechanisms in healthy individuals, thereby enhancing high-quality cognitive activities and the effectiveness of cognitive rehabilitation training. This study involved 48 healthy adults aged 20-35 and was conducted in two phases: cognitive fatigue validation and whole-brain connectivity feature analysis. We used fMRI to compare Amplitude of Low-Frequency Fluctuations (ALFF), Regional Homogeneity (ReHo), Functional Connectivity (FC), and graph theory metrics before and after cognitive fatigue. The results indicated that changes in activity within the bilateral thalamus and Front-Parietal network were significantly correlated with subjective fatigue levels. Additionally, the left precuneus, cerebellum, and certain frontal regions may contribute to the neural regulation of cognitive fatigue through various mechanisms. These findings provide a reliable theoretical basis for developing new strategies to mitigate cognitive fatigue and offer valuable insights for optimizing rehabilitation plans for patients with cognitive impairments.

Photobiomodulation can alleviate the severity or delay the development of cognitive impairment through early prevention and intervention. This systematic review summarizes the effectiveness of photobiomodulation in improving cognitive function across various populations. Clinical randomized controlled trials from the establishment of the database to October 2024 were searched in PubMed, Web of Science, EMBASE, and the Cochrane Library according to PRISMA guidelines. Trials comparing the effects of PBM treatment with placebo or sham stimulation on cognitive function in healthy adults or subjects with cognitive impairment were included. Two independent researchers conducted literature screening, data extraction, and quality assessment of the included studies. Meta-analyses were performed using random effects models with Review Manager V.5.4 software. The methodological quality of the studies was evaluated using the Cochrane Risk of Bias tool. Sensitivity analyses were performed using Stata V.15.1 software. A total of 24 randomized trials involving 820 participants met the inclusion criteria. Compared with the control group, PBM treatment showed significant benefits for subjects in terms of global cognitive function (SMD = 0.66, 95

OBJECTIVE:This investigation was designed to analyze alterations in functional connectivity across brain networks associated with cognitive fatigue through electroencephalogram (EEG) data analysis. Through the application of both global and local graph-theoretical metrics to characterize the topology of brain networks, this study establishes a conceptual framework supporting enhanced detection of cognitive fatigue manifestations while facilitating examination of its neurophysiological substrates. METHODS:The study cohort comprised neurologically intact individuals aged 20-35 years, recruited from Beijing Rehabilitation Hospital, Capital Medical University between February 6 and September 30, 2024 for participation in a cognitive fatigue induction task. Following acquisition of written informed consent, data before and after the task were obtained, including both subjective fatigue assessments using the Visual analog scale for fatigue (VAS-F) scores and EEG data. The preprocessed EEG signals were segmented into three frequency bands: θ (4-8 Hz),α (8-13 Hz), and β (13-30 Hz). To determine the frequency band exhibiting maximal sensitivity to cognitive fatigue, cross-band comparative power spectral density (PSD) was implemented. The selected frequency band subsequently served as the basis for weighted Phase Lag Index (wPLI) computation, yielding a functional connectivity matrix derived from wPLI measurements. Network topology was evaluated through application of five global graph theory metrics (global efficiency [Eg], local efficiency [Eloc], clustering coefficient [Cp], shortest path length [Lp], and small-world property [Sigma]) complemented by two local graph theory metrics (nodal efficiency [NE] and degree centrality [DC]). This analytical framework enabled systematic comparison of connectivity patterns and topological characteristics between before and after cognitive fatigue states. RESULTS:Statistical analysis revealed significant post-fatigue elevations in global average PSD across all examined frequency bands: α (p < 0.001), θ (p < 0.001), and β (p = 0.004). The α band demonstrated the most pronounced effect size (Cohen's d = 4.23, r = 0.90). Topological analysis of α-band wPLI networks showed enhanced Eg (p = 0.005), Eloc (p < 0.001), and Cp (p < 0.001), whereas Lp displayed significant reduction (p = 0.005). Regional analysis revealed preferential enhancement of NE, particularly in central and anterior cortical regions. CONCLUSION:The experimental data indicated that α-band activity exhibited the highest sensitivity to cognitive fatigue induced by the sustained Stroop task, establishing a framework for accurate identification of fatigue states. Cognitive fatigue compensatory mechanisms manifested as concurrent improvements in both local and global neural information processing efficiency. Although such adaptive reorganization may compromise overall network efficiency, these findings implied an inherent balance between adaptive network reconfiguration and system efficiency. These results elucidated novel neurophysiological mechanisms underlying cognitive fatigue, substantially advancing our understanding of brain network dynamics during prolonged cognitive demand.

Alzheimer's disease (AD) yields a dramatic burden on patients and their families, with no complete cure yet. Our group has previously found that AD-related cognitive impairment (ARCI) could be alleviated after luteolin and exercise combination treatment (Lut + Exe), but the potential mechanisms require further exploration. This work used untargeted metabolomics to uncover the mechanisms Lut + Exe protects against ARCI. Utilizing an Aβ1-42-oligomers-induced AD model, the Morris water maze (MWM) test was performed. Metabolomics of plasma was performed to identify differential metabolites. KEGG and MetaboAnalyst were used to enrich the metabolic pathways. Then, the autophagy inhibitor chloroquine (CQ) was utilized to verify the potential role of autophagy in the Lut+ Exe efficacy against ARCI. The results showed that Lut + Exe alleviated the ARCI in mice. The in-depth analysis showed that Lut + Exe could significantly affect purine metabolism, retinol metabolism, thiamine metabolism, histidine metabolism, and cysteine and methionine metabolism, indicating that the energy metabolism disorder was alleviated. Based on the close relationship between autophagy and energy metabolism, further study found that Lut + Exe could reverse the significant reduction of key autophagy proteins of AD model mice, while the effects of it on the MWM performance and neurogenesis of AD model mice could be blocked by CQ. This study reveals the crucial role of autophagy in the mechanisms of Lut + Exe against ARCI using untargeted metabolomics. Our work provides a novel paradigm to promote the use of combination treatment in curing AD.

Cognitive impairment has emerged as a major public health challenge of the elderly in China. Addressing this urgency, advancing evidence-backed, accessible and scalable non-pharmacological intervention frameworks is no longer optional but a pressing priority for clinical practice. This consensus focuses on the common non-drug intervention means of cognitive impairment in clinical practice, such as neuroregulation technology, exercise intervention, cognitive training, diet intervention, social psychotherapy, and traditional Chinese medicine therapy, and systematically combs the evidence-based medical evidence in related fields in the past ten years, aiming to provide more diversified and effective treatment means for patients with cognitive impairment and provide scientific guidance for clinical practice of cognitive impairment.

Background:Age-related cognitive problems are becoming increasingly prevalent in older adults; thus, maintaining normal cognitive abilities and delaying cognitive decline are essential for promoting healthy aging.Methods:This systematic review and network meta-analysis examined the effects of combining cognitive and physical training by including various exercise components to improve memory and executive function in older adults. The Cochrane Risk Assessment Tool was used to assess the risk of bias in the included literature. Pairwise meta-analysis was conducted using RevMan 5.3, while network meta-analysis was performed with Stata 15.1, and interventions were ranked based on the results.Results:A total of 8180 articles were screened, and 16 randomized controlled trials were included. Pairwise meta-analysis showed that cognitive-physical interventions with 2 (SMD = 0.26, 95% CI: 0.07-0.44, P = .007) and 3 or more exercise components (SMD = 0.43, 95% CI: 0.13-0.73, P = .004) significantly improved memory compared to controls. For executive function, both interventions with 2 (SMD = 0.40, 95% CI: 0.15-0.65, P = .002) and 3 or more exercise components (SMD = 0.55, 95% CI: 0.16-0.93, P = .005) outperformed the control group. Network meta-analysis confirmed that interventions with 2 (SMD = 0.24, 95% CI: 0.06-0.42) and 3 or more components (SMD = 0.43, 95% CI: 0.13-0.73) improved memory, while a single exercise component was most effective for executive function (SMD = 1.27, 95% CI: 0.05-2.49). Overall, we demonstrated that combined cognitive-physical intervention training with multiple exercise components significantly improved memory and executive function compared to controls. The effects of combined training with 3 or more exercise components were likely the most effective in improving memory.Conclusion:Cognitive-physical combined interventions are increasingly applied in clinical research on age-related cognitive decline. Our meta-analysis indicates that interventions incorporating multiple exercise components are more effective than those with a single exercise component. These findings provide a basis for future cognitive and physical interventions for older adults and can inform the design of effective intervention programs.

Recent advances in flexible exoskeleton technology have broadened its application in stroke rehabilitation, particularly for improving motor functions in the affected lower limb. This review examines the impact of flexible exoskeleton-assisted training (FEAT) compared to conventional therapy on balance, motor functions, and gait parameters in post-stroke patients. We conducted a meta-analysis using data from randomized controlled trials (RCTs) identified through database searches and manual screening, focusing on outcomes such as balance (Berg Balance Scale, BBS), lower limb motor functions (Ten-Meter Walk Test, 10MWT; Six-Minute Walk Test, 6MWT; Functional Ambulation Category, FAC), and gait parameters (walking speed, step length, cadence, and symmetry). This meta-analysis included 6 studies with 213 patients. FEAT significantly enhanced BBS scores, and performances on the 10MWT and 6MWT, along with other gait parameters; however, FAC scores did not improve significantly. Subgroup analyses revealed that FEAT with hip assistance significantly improved step length, cadence, and gait symmetry ratio, while ankle assistance improved performance on the 10MWT and 6MWT. FEAT was especially effective in improving step length, cadence, and gait symmetry ratio in patients with a post-stroke duration exceeding three months. Compared to the conventional therapy, FEAT markedly improves the balance, walking ability, and gait parameters in stroke rehabilitation. These findings support the value of FEAT in lower extremity rehabilitation post-stroke, suggesting its integration into clinical programs could enhance the therapy effectiveness or efficiency. In addition, the appropriate type of FEAT needs to be selected in the rehabilitation program based on the patient’s specific impairment. For example, FEAT with hip assistance may be recommended for stroke patients with severe gait asymmetry, aiding the development of personalized interventions.

The outcome of robotic-assisted training can be enhanced by controlling the robot using the user's own motion. Electromyography (EMG) signals have been used to detect motions based on muscle activities. However, spasticity-induced involuntary muscle activities can be a main factor compromising the accuracy of motion detection for post-stroke patients. This study therefore aimed to quantify the effect of Botulinum toxin type A (BoNT-A) treatment on the accuracy of EMG-based motion detection for post-stroke patients with spasticity. Four stroke patients who received BoNT-A treatment on their flexor digitorum superficialis muscle due to moderate or severe spasticity were recruited in this study. High-density surface EMG signals of hand closing were recorded before BoNT-A treatment and two weeks afterwards. Threshold-based method was used to detect motions, and motion detection accuracy was calculated for each subject before and after BoNT-A treatment. Increased accuracy of motion detection was observed after treatment. The findings of this study provide evidence that muscle spasticity reduction by BoNT-A treatment may improve motion detection, and can improve the interaction experience of robot-assisted stroke rehabilitation by reducing the chance of unintended triggering.

The risk of developing chronic illnesses and disabilities is increasing with age. To predict and prevent aging, biomarkers relevant to the aging process must be identified. This paper reviews the known molecular, cellular, and physiological biomarkers of aging. Moreover, we discuss the currently available technologies for identifying these biomarkers, and their applications and potential in aging research. We hope that this review will stimulate further research and innovation in this emerging and fast-growing field.

Background Occupational hazards occur in all walks of life. China’s horticulture industry is undergoing rapid development. However, the mental health of garden workers has not received much attention. This study investigates the mental health status and influencing factors of Chinese garden workers and provides a basis for promoting their mental health and ensuring the healthy development of Chinese horticulture. Methods A cross-sectional survey of garden workers in Beijing was conducted from 10 July 2021 to 10 October 2021. A total of 3349 valid questionnaires were recovered, with an effective response rate of 95.69%. Descriptive statistical analysis was carried out on the demographic characteristics, job satisfaction, stress, anxiety, and depression of garden workers, and the influencing factors affecting the mental health of Chinese garden workers were found through a t-test, variance analysis, and ordinal multi-class logistic regression analysis. Results Survey respondents were mostly male (54.4%) and under the age of 40 (64.1%). The anxiety and depression symptoms of the garden workers were moderate. Among staff members, 40.2% were in a normal state of stress. Gender, three meals on time, monthly income, and job satisfaction were the factors influencing stress, anxiety, and depression symptoms among garden workers. Conclusion Compared to medical staff and other groups, the stress, anxiety, and depression symptoms of Chinese garden workers are severe. Gender, monthly income, and job satisfaction are important factors affecting their mental health. Managers should continuously improve the working environment of garden workers, provide salaries that match their positions, and improve their job recognition and satisfaction to reduce the impact of negative emotions on personal health.