Background: The growing burden of cognitive decline represents a significant public health concern in aging populations, particularly in China. Social participation is a modifiable factor that may protect against cognitive decline, yet its long-term dynamic association with cognitive impairment remains insufficiently characterized. Objectives: This study aimed to delineate long-term trajectories of social participation and determine their association with cognitive impairment in Chinese older adults. Design: : Longitudinal cohort study. Setting: The study utilized data collected in 2013, 2015, and 2018 from the China Health and Retirement Longitudinal Study. Participants: We included 3074 Chinese adults aged ≥60 years who were free of cognitive impairment in 2013, had complete social participation data in 2013/2015/2018, and completed cognitive assessments in 2018 Intervention(s): Not applicable. Measurements: Social participation was derived from CHARLS self-reported activity items and frequency and summed into a composite score (range 0–33). Cognitive performance was assessed using episodic memory (immediate and delayed 10-word recall) and mental status (orientation, serial subtraction, and figure drawing), yielding a global score (range 0–31); cognitive impairment was defined as a score <11. Group-based trajectory modeling identified five social participation trajectories. Multivariable logistic regression estimated odds ratios (ORs) for cognitive impairment adjusting for sociodemographic, health, and behavioral covariates. Results: Five distinct social participation trajectories were identified. In the fully adjusted model, relative to the “stable low” group, those in the “low baseline–increasing” (OR = 0.66, 95% CI: 0.47–0.92), “stable intermediate” (OR = 0.75, 95% CI: 0.58–0.97), and “stable high” (OR = 0.41, 95% CI: 0.22–0.76) groups had markedly reduced chances of cognitive impairment, while no significant link was found for the “moderate decline” group (OR = 0.90, 95% CI: 0.71–1.17). Conclusions: Maintaining or increasing one’s social activities was linked to a notably lower likelihood of cognitive decline. These results highlight the importance of social involvement patterns as a modifiable factor for fostering cognitive strength. Interventions to maintain or enhance participation are therefore a viable strategy for the primary prevention of cognitive decline in older adults.

Exercise is recommended for cancer survivors, yet participation remains low and its modifiable correlates in working-age survivors are poorly characterized. We examined cross-sectional associations between exercise participation and 12 health outcomes and estimated cross-sectional indirect associations between psychological resources and exercise operating through commitment to an active lifestyle. We analyzed 3,028 working-age US cancer survivors. Exercise was assessed with a single binary item (any regular weekly activity). Twelve symptom and functional outcomes were regressed on exercise status, adjusting for ten sociodemographic covariates with false discovery rate correction. Hierarchical logistic regression evaluated four predictor blocks: sociodemographics, employment, motivational factors (commitment, risk awareness), and psychological resources (self-efficacy, hope, core self-evaluations). Bootstrapped analyses tested cross-sectional indirect associations involving psychological resources, commitment, and exercise participation. Commitment was the strongest correlate of exercise (OR = 2.58, 95

BACKGROUND:Working memory impairment has been reported in older adults with sleep disorders and MCI, with the frontoparietal network playing a central role in working memory. The key question is whether integrating Tai Chi with rTMS improves working memory, and whether such improvements result from the modulation of frontoparietal networks plasticity. METHODS:Seventy-one participants with sleep disorders and MCI were assigned to the experimental group (Tai Chi + 1-Hz rTMS, n = 37) or sham group (Tai Chi + sham rTMS, n = 34). They completed 6 weeks of Tai Chi combined with neuronavigated rTMS targeted the right DLPFC and underwent fMRI scans. Outcomes included Numerical N-back task, digit span task，Pittsburgh Sleep Quality Index (PSQI), Montreal Cognitive Assessment (MoCA). Task fMRI measured N-back activation patterns, and seed-based resting-state functional connectivity (rsFC) was assessed. Correlations between the activation/rsFC and N-back task performance were explored. RESULTS:Seventy-one participants (mean age 67.6 ± 4.6 years; 30 male [42%], 41 female [58%]) were included. After 6 weeks, the experimental group showed significant improvements versus shams in PSQI, MoCA, 0-back and 2-back task accuracy, 0-back reaction time, and forward digit span (all p < 0.05). The 2-back accuracy was negatively correlated with right precuneus activation (r = -0.381, p = 0.034) and positively correlated with right precuneus connectivity to the left SMA (r = 0.367, p = 0.042). CONCLUSION:Adjunctive neuronavigated rTMS delivered in addition to Tai Chi training may enhance working memory rehabilitation in older adults with sleep disorders and MCI, with frontoparietal network modulation as a potential neural basis. TRIAL REGISTRATION:Clinical trial registration no. ChiCTR 2200063274.

ABSTRACT:Alzheimer's disease is characterized by impairment in episodic memory and visuospatial skills, which is related to the deterioration of glutamatergic synapses within the entorhinal cortex-hippocampal circuit. While electroacupuncture shows therapeutic promise for Alzheimer's disease, its underlying mechanisms remain poorly understood. This study investigated whether the effects of electroacupuncture on spatial memory involves improving synaptic plasticity in this circuit using triple-transgenic Alzheimer's disease mice. The intervention consisted of a 4-week daily electroacupuncture treatment at DU20/DU24 acupoints or sham treatment. Our findings revealed that electroacupuncture triggered a cascade of neuroplastic events, leading to significant cognitive improvements. Crucially, these therapeutic effects were completely abrogated by chemogenetic inhibition of the entorhinal cortex-hippocampal CA1 circuit, establishing its causal necessity. Our multi-level analyses revealed that electroacupuncture attenuated tau hyperphosphorylation, restored dendritic spine density, and boosted long-term potentiation. This was accompanied by an increase in crucial synaptic proteins and activation of the NMDAR-CaMKII-CREB signaling cascade. The key findings of this study reveal a multi-level neurorestorative cascade induced by electroacupuncture, by simultaneously reducing tau pathology, rebuilding synaptic architecture, and enhancing synaptic function in the entorhinal-hippocampal circuit, driven by the NMDAR-CaMKII-CREB pathway. Collectively, these results provide evidence that electroacupuncture ameliorates spatial memory deficits in Alzheimer's disease model mice by specifically enhancing synaptic plasticity in the entorhinal cortex-hippocampal circuit.

Cognitive frailty (CF), characterized by concurrent cognitive and motor decline, is a major challenge to healthy aging, yet effective interventions remain limited. Klotho, an anti-aging protein that declines with age, has been implicated in both hippocampal function and skeletal muscle homeostasis. In this study, we investigated whether aerobic exercise combined with multisensory stimulation training (CT) ameliorates age-related CF through systemic Klotho signaling. A 16-month-old mouse model of age-related CF was assigned to aerobic training, multisensory stimulation, or combined training, and behavioral, electrophysiological, histological, and molecular assessments were performed. To examine the mechanistic role of Klotho, dual-route shRNA delivery was used to inhibit systemic Klotho expression. CT significantly improved cognitive and motor performance compared with either intervention alone. CT also increased hippocampal dendritic spine density and long-term potentiation, reduced collagen deposition in gastrocnemius muscle, and upregulated Klotho, FGF19, and FGFR1 expression in both hippocampus and muscle, accompanied by elevated serum Klotho levels. Klotho knockdown attenuated these beneficial effects, reduced PSD95 and GluN2B expression, and increased MuRF3 and TNF-α levels. These findings suggest that CT alleviates cognitive frailty and that systemic Klotho is a key mediator linking hippocampal synaptic function and skeletal muscle homeostasis.

Background and aim The traditional Chinese formula Shanyu Wan (SYW), comprising Panax ginseng, Dioscorea opposita Thunb and Atractylodes Rhizoma, has been empirically employed for metabolic regulation, although its mechanistic basis remains incompletely elucidated. Experimental procedure Senescence-accelerated mouse prone 8 (SAMP8) mice were orally administered SYW by gavage at 2.56 g/kg for 8 weeks, with age-matched senescence-accelerated mouse resistant 1 (SAMR1) mice serving as controls. Muscle phenotype was evaluated by forelimb grip strength, rotarod performance, spontaneous locomotor activity, and magnetic resonance imaging (MRI). Histopathological alterations were evaluated by Masson's trichrome staining. Mitochondrial ultrastructure was examined by transmission electron microscopy (TEM), and mitochondrial functional parameters were subsequently determined. Furthermore, the effects of SYW-containing serum on oxidative injury were examined in t-BHP-treated C2C12 myoblasts, together with pharmacological interference analysis of PGC-1α-related signaling. Results and conclusion Oral administration of SYW significantly improved muscle volume, grip strength, and motor performance in SAMP8 mice. These protective effects were accompanied by partial restoration of mitochondrial ultrastructure, increased mitochondrial respiratory chain complex activity, reduced oxidative stress, and changes in PGC-1α-related signaling. In vitro, SYW-containing serum attenuated t-BHP-induced oxidative and mitochondrial injury in C2C12 myoblasts, while pharmacological interference experiments suggested the involvement of PGC-1α-related signaling. These findings provide preclinical evidence that SYW may alleviate age-related muscle alterations by improving mitochondrial function and redox balance.

ABSTRACT Alzheimer's disease (AD) is characterized by progressive cognitive decline and cerebral glucose hypometabolism. Emerging evidence suggests that modulating brain glucose metabolism represents a promising therapeutic strategy for AD. Here, we demonstrate that electroacupuncture (EA) improves cognitive function in 5×FAD mice by enhancing glucose metabolism in the hippocampus. EA treatment significantly attenuated learning and memory deficits and reduced β‐amyloid (Aβ) deposition in 5×FAD mice. Further analysis revealed that these improvements were associated with enhanced hippocampal glucose metabolism and optimized information processing in the brain metabolic network. In addition, EA specifically activated the IGF1/IGF1R signaling pathway in the hippocampus, which promoted membrane translocation of GLUT3 and consequently enhanced neuronal glucose uptake. The glucose metabolic enhancement boosted tricarboxylic acid cycle activity and improved synaptic plasticity. Our findings establish a novel mechanism by which EA improves the learning and memory through the IGF1/IGF1R pathway, providing both theoretic and experimental support for the clinical application of EA in AD treatment.

Background Working memory deficits, one of the earliest hallmarks of Alzheimer’s disease (AD), are closely linked to abnormal neural activity in the dorsolateral prefrontal cortex (DLPFC). Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation therapy, has been shown to ameliorate early AD working memory deficits by modulating excitatory activity in the DLPFC, yet the underlying mechanisms remain incompletely understood. Methods This investigation was structured around 3 experimental phases. We initially applied tDCS to stimulate the left prefrontal cortex (PFC) of transgenic mice with 5 familial AD (5×FAD) 5 d per week for 4 weeks. Subsequently, we employed optogenetic (Opt) techniques to modulate left PFC glutamatergic neurons. Finally, we inhibited soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) expression in the left PFC to elucidate the essential function of SNARE complex assembly with chaperone molecules in orchestrating synaptic vesicle release. Results tDCS treatment improved working memory deficits in early-stage AD mice. This was accompanied by increased cerebral blood flow, enhanced neuronal excitability, amelioration of neurochemical metabolic disorders, and reduced amyloid β-protein (Aβ) deposition in the left PFC. Opt stimulation of PFC glutamatergic neurons similarly improved working memory, indicating the association between tDCS’s therapeutic effects and synaptic plasticity of excitatory neurons. Crucially, tDCS facilitated synaptic vesicle fusion and release, evidenced by increased vesicle numbers, enhanced release probability, improved synaptic transmission efficacy, and upregulation of the SNARE complex, Snap25, and Syt1. Inhibiting SNARE expression in the left PFC attenuated the tDCS-induced improvements in synaptic vesicle release and working memory. Conclusion These findings collectively demonstrate that left PFC-targeted tDCS modulates interactions between the SNARE complex and chaperone molecules, thereby promoting synaptic vesicle fusion and release. This mechanism underlies the amelioration of early AD-like working memory impairment by tDCS.

Long-term regular exercise is effective against age-related cognitive decline. However, the mechanisms through which mind-body exercises such as Tai Chi produce these effects, and the involvement of exosome-mediated signaling between the periphery and the brain, are unknown. For this 1:1 matched observational study, cognitively normal participants aged 60 to 75 years, with a male-to-female ratio of 2:3, were recruited into the long-term regular Tai Chi group (n = 50) and long-term irregular exercise group (n = 50). N-back task functional magnetic resonance imaging revealed that the long-term regular Tai Chi group showed a better working memory performance than the long-term irregular exercise group. Moreover, the long-term regular Tai Chi group showed altered activation in the superior frontal gyrus and pre/postcentral gyri. By integrating microRNA sequencing and proteomic profiling of serum exosomes, we identified miR-625-5p as a significant differential factor targeting CALM1 and VDAC2, whose expression levels negatively correlated with 1-back task accuracy. To investigate causality, serum-derived exosomes from both groups were delivered intravenously to SAMP8 mice. Exosomes from the Tai Chi group improved working memory deficits and resulted in an increase in prefrontal dendritic spine density, while down-regulating miR-625-5p and up-regulating the synaptic plasticity-related proteins calmodulin 1 and voltage-dependent anion channel 2 in the prefrontal cortex. Collectively, our findings suggest that long-term Tai Chi exercise may improve cognitive function by remodeling circulating exosome cargo. The key mediator, miR-625-5p, may act via the calmodulin 1/voltage-dependent anion channel 2 pathway to orchestrate prefrontal synaptic remodeling. Exosomes derived from Tai Chi practitioners may be a potential therapy for age-related cognitive decline.

BACKGROUND:Early identification of individuals who progress from normal cognition (NC) to mild cognitive impairment (MCI) may help prevent cognitive decline. We aimed to build predictive models using radiomic features of the bilateral hippocampus in combination with scores from neuropsychological assessments. METHODS:We utilized the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to study 175 NC individuals, identifying 50 who progressed to MCI within seven years. Employing the Least Absolute Shrinkage and Selection Operator (LASSO) on T1-weighted images, we extracted and refined hippocampal features. Classification models, including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), and light gradient boosters (LightGBM), were built based on significant neuropsychological scores. Model validation was conducted using 5-fold cross-validation, and hyperparameters were optimized with Scikit-learn, using an 80:20 data split for training and testing. RESULTS:We found that the LightGBM model achieved an area under the receiver operating characteristic (ROC) curve (AUC) value of 0.89 and an accuracy of 0.79 in the training set, and an AUC value of 0.80 and an accuracy of 0.74 in the test set. CONCLUSION:The study identified that T1-weighted magnetic resonance imaging radiomic of the hippocampus would be used to predict the progression to MCI at the normal cognitive stage, which might provide a new insight into clinical research.

Building upon established short-term benefits, this study aimed to assess Tai Chi’s durability for preserving global and domain-specific cognition in older adults (≥ 60 years) with type 2 diabetes and mild cognitive impairment (T2D-MCI), compared to fitness walking and health education. Participants (n = 328) were randomized 1:1:1 to Tai Chi, fitness walking, or health education groups, completing 24-week interventions. Cognitive outcomes—global cognition (Montreal Cognitive Assessment, MoCA), executive function, attention, visuospatial ability, and language fluency—were evaluated at baseline, 24 weeks(post-intervention), 36 weeks, and 2 years. Linear mixed models analyzed group-by-time interactions, while time-dependent Cox regression quantified minimal clinically important difference (MCID) attainment (MoCA improvement ≥ 4 points). At 2-year follow-up, linear mixed models revealed significant group-by-time interactions for MoCA (p < 0.001). The Tai Chi group showed greater MoCA improvement versus health education (mean difference: 1.8, 95

Physical exercise protects against cognitive impairment caused by chronic cerebral hypoperfusion (CCH). However, the mechanisms through which exercise sends signals from the periphery to the central nervous system remain incompletely understood. This study demonstrated that exercise promotes the secretion of muscle-derived small extracellular vesicles (sEVs), which facilitate interorgan communication between the muscle and the brain. Systematic delivery of muscle-derived sEVs enhances synaptic plasticity and alleviated cognitive impairment in CCH. Notably, miRNA sequencing reveal miR-17/20a-5p as key cargos in sEVs involved in the exercise-induced muscle-brain crosstalk. Muscle-derived sEVs are also identified as the primary source of swimming-induced miR-17/20a-5p in circulating sEVs. Mechanistically, miR-17/20a-5p binds to the DEP-domain containing mTOR-interacting protein (DEPTOR) and activates the mammalian target of rapamycin (mTOR) pathway in the hippocampus. Depletion of miR-17/20a-5p from muscle-derived sEVs impairs the exercise-induced enhancement of synaptic plasticity and cognitive function. Moreover, overexpression of DEPTOR in the hippocampus attenuates the cognitive benefits of exercise. Conversely, hippocampus-specific activation of mTOR reverses these effects, highlighting the crucial role of mTOR in mediating the positive effects of exercise. Collectively, these findings identify miR-17/20a-5p in muscle-derived sEVs as the exercise-induced myokine with potent effects on the brain, emphasizing the therapeutic potential of exercise in managing cognitive impairment.

Deterioration of cognitive function with aging is a significant public health issue, particularly in individuals with diabetes mellitus (DM). Exercise has been shown to enhance cognitive function. However, the threshold effect of physical activity on cognitive function in older adult people with DM remains unclear. This study analyzed data from 925 older participants (aged 60 and above) derived from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2014, representing a total weighted respondent count of 13,824,651. Cognitive function was evaluated with the Animal Fluency test (AFT) and Digit Symbol Substitution test (DSST). To assess the relationship between physical activity and cognitive function, we applied weighted linear regression models coupled with restricted cubic spline analysis. Furthermore, a two-piecewise linear regression model was utilized to detect any potential threshold effect of exercise on cognitive function. The results indicated a positive correlation between physical activity and cognitive function scores on the AFT and DSST after adjusting for potential confounders. Threshold analyses showed a consistent positive relationship for AFT scores at less than 490 MET-min/week of physical activity [β (95

Ischemic stroke caused motor dysfunction results poses substantial health burdens and socioeconomic challenges. Electro-acupuncture (EA) at the acupoints of Quchi (LI11) and Zusanli (ST36) has shown positive efficacy in motor dysfunction after stroke. Considering the reported functions of the GABAergic system in locomotion, the present study aims to investigate the detailed mechanism of EA effects on motor regulation, focusing on the neural histological and chemical changes in the GABAergic system. Results demonstrated that EA at LI11 and ST36 improved the modified neurological severity score (mNNS) score and motor function of MCAO/R rats. EA at LI11 and ST36 also prompted γ-aminobutyric acid-ergic (GABAergic) system by the expression of GABA related receptors and GABA interneurons. Here, We have identified long-range projecting GABAergic interneurons, which can be classified into different subtypes based on the molecular markers they express: Parvalbumin (PV+), Somatostatin (SST+), and Vasoactive Intestinal Peptide (VIP+). Additionally, optogenetic stimulation of this projecting neurons can improve the motor dysfunction of MCAO/R rats. Notably, cortex M1-striatum (CS)-SST neural circuit which showed an indescribable role in locomotion improvement under EA intervention. The downregulation of the type II dopamine receptor in medium-sized spiny neurons (DR2-MSNs) and the upregulation of Synaptophysin (SYN) and Postsynaptic Density-95 (PSD95) suggest that MSNs and synaptic plasticity might be the downstream mechanisms of EA treatment at LI11 and ST36. To conclude, EA at LI11 and ST36 can promote synaptic plasticity and improve motor function by targeting and regulate downregulated DR2-MSNs neurons through the CS-SST neural circuit.

BACKGROUND:Successful aging involves maintaining physical vitality, emotional health, and meaningful social connections throughout late life. Body Roundness Index (BRI), a numerical indicator of body shape, is drawing growing interest as a potential marker for evaluating successful aging. Drawing on data from the China Health and Retirement Longitudinal Study (CHARLS), this research examined how BRI trajectory patterns were associated with successful aging in the older Chinese population. METHODS:The analysis included 2517 individuals aged 60 and above, drawn from the CHARLS cohort. BRI was measured in 2011, 2013, and 2015, and its longitudinal patterns were determined through group-based trajectory modeling (GBTM). Successful aging was assessed at the 2018 follow-up. To investigate the link between BRI trajectories and successful aging, we employed binary logistic regression, supplemented by subgroup and interaction analyses to test for effect modification. FINDINGS:Three distinct BRI trajectories were identified: low-stable (46.9 %), intermediate-stable (43.0 %), and high-rising (10.1 %). The intermediate-stable group had the greatest odds of successful aging compared to the high-rising group, followed by the low-stable group with a moderately lower likelihood. Upon controlling for a range of covariates, individuals in the intermediate-stable group and the low-stable group had significantly greater odds of successful aging, with ORs of 2.63 (95 % CI: 1.45-5.12, P = 0.002) and 2.52 (95 % CI: 1.26-5.31, P = 0.012), respectively. Across sensitivity analyses, the intermediate-stable trajectory showed the strongest and most consistent association with successful aging. CONCLUSION:This study highlights the need to monitor body changes in older adults and develop targeted health strategies to support successful aging.

Objective To observe the effect of electroacupuncture(EA)on learning and memory in rats with middle cerebral artery occlusion/reperfusion(MCAO/R)by regulating ferritinophagy through the cyclic GMP-adenosine synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.Methods SD rats were randomly divided into a normal group,a model group,and an EA group.Except for the normal group,all rats underwent MCAO/R by suture occlusion.The EA group received treatment at"Shenting"(GV24)and"Baihui"(GV20)for 30 min once daily for 14 d.The Zea-Longa score was used to assess neurological deficits in rats.The Morris water maze test and the new object recognition test were used to evaluate the learning and memory abilities of rats.The elevated plus maze test was used to evaluate the anxiety state of rats.The TTC staining was used to measure the infarct volume of rats.The HE staining method was used to observe pathological changes in rat's brain tissue.Iron deposition in the hippocampus was assessed with Prussian blue staining.Mitochondrial morphology in the hippocampus of rats was observed using transmission electron microscopy.Western blot was used to detect the protein expression levels of cGAS,STING,nuclear receptor coactivator 4(NCOA4),ferritin heavy chain 1(FTH1),P62,Beclin1,and the ratio of micro tubule-associated protein 1 light chain 3(LC3)Ⅱ/LC3Ⅰ in the hippocampus of rats.Real-time fluorescence quantitative PCR was used to detect the mRNA expression levels of interferon regulatory factor 3(IRF3),TANK-binding kinase 1(TBK1),Interleukin-10(IL-10),Interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in the hippocampus of rats.Results Compared with the normal group,the neurological deficit scores,infarct volume,escape latency,time to explore old objects,and the expression levels of cGAS,STING,NCOA4,Beclin1,and the ratio of LC3Ⅱ/LC3Ⅰproteins,as well as IRF3,TBK1,IL-1β,and TNF-α mRNAs were increased(P<0.01)in the model group;the number of times crossing the original platform,the time spent exploring new objects,cognitive index,the percentage of time spent in the open arms,the percentage of times spent in the open arms,and the expression levels of FTH1,P62 proteins,and IL-10 mRNA were decreased(P<0.01).The model group displayed sparse hippocampal CA1 neurons,fewer cells,disorganized structure,and evident brownish iron deposition.Mitochondria appeared swollen with disrupted cristae.Compared with the model group,the EA group showed reduced neurological deficit scores,infarct volume,escape latency,time to explore old objects,and the expression levels of cGAS,STING,NCOA4,Beclin1,and the ratio of LC3Ⅱ/LC3Ⅰ,IRF3,TBK1,IL-1β,and TNF-α mRNAs(P<0.05,P<0.01).Meanwhile,the number of times crossing the original platform,the time spent exploring new objects,cognitive index,the percentage of time spent in the open arms,the percentage of times spent in the open arms,and the expression levels of FTH1,P62 proteins,and IL-10 mRNA increased in the EA group(P<0.01,P<0.05).The EA group showed improved neuronal arrangement in the hippocampal CA1,with uniform cell spacing and more regular cell morphology.Iron deposition was reduced.Mitochondria demonstrated improved morphology,with less cristae dissolution but no obvious rupture,appearing more normal and structurally intact.Conclusion EA can improve the learning and memory abilities of MCAO/R rats,and its mechanism may be related to the inhibition of ferritinophagy mediated by the cGAS-STING signaling pathway.

ImportanceSleep disorders and mild cognitive impairment (MCI) commonly coexist in older adults, increasing their risk of developing dementia. Long-term tai chi chuan has been proven to improve sleep quality in older adults. However, their adherence to extended training regimens can be challenging. Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulation technique that may enhance the benefits of exercise.ObjectiveTo investigate whether 1-Hz rTMS of the right dorsolateral prefrontal cortex could enhance the clinical benefits of tai chi chuan in improving sleep quality and cognitive function among older adults with sleep disorders and MCI.Design, Setting, and ParticipantsThis 2-arm, sham-controlled, assessor-masked randomized clinical trial was conducted at a university hospital in China between October 2022 and February 2024. Adults aged 60 to 75 years with sleep disorders and MCI were eligible. Data analysis was performed from February to May 2024.InterventionParticipants were randomized in a 1:1 ratio to an experimental group (tai chi chuan and 1-Hz rTMS) or a sham group (tai chi chuan and sham rTMS). Each participant received 30 sessions of personalized rTMS targeting the right dorsolateral prefrontal cortex, and the sham group underwent the same procedure. The 2 groups received 30 sessions of 60 minutes of the 24-form simplified tai chi chuan, 5 times per week for 6 weeks.Main Outcomes and MeasuresThe primary outcomes were subjective sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI), in which scores range from 0 to 21, with lower scores indicating a healthier sleep quality, and global cognitive function assessed by the Montreal Cognitive Assessment (MoCA), in which scores range from 0 to 30, with higher scores indicating less cognitive impairment. The secondary outcomes included measures of objective sleep actigraphy, anxiety and depression scales, and other cognitive subdomains. Assessments were performed at baseline, 6 weeks after the intervention, and at the 12-week follow-up.ResultsA total of 110 participants (mean [SD] age, 67.9 [4.6] years; 68 female [61.8%]) were randomized to the experimental group (n = 55) and the sham group (n = 55) and included in the intention-to-treat analysis. At 6 weeks after the intervention, compared with the sham group, the experimental group showed a lower PSQI score (between-group mean difference, −3.1 [95% CI, −4.2 to −2.1]; P < .001) and a higher MoCA score (between-group mean difference, 1.4 [95% CI, 0.7-2.1]; P < .001). The per-protocol dataset analyses and 12-week follow-up showed similar results. The generalized estimated equation model revealed an interaction effect between the PSQI score (mean difference, −2.1 [95% CI, −3.1 to −0.1]; P < .001) and the MoCA total score (mean difference, 0.9 [95% CI, 0.1-1.6]; P = .01). There were 7 nonserious, unrelated adverse events (experimental group: 2; sham group: 5) with no significant difference between the 2 groups.Conclusions and RelevanceIn this randomized clinical trial, the findings suggest that 1-Hz rTMS enhanced the clinical benefits of tai chi chuan in improving sleep quality and cognitive function among older adults with sleep disorders and MCI, which may be related to alterations in neural plasticity. These findings provide novel data on nonpharmacologic strategies for the rehabilitation of sleep disorders and may delay or even prevent MCI.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2200063274

Background:Tai Chi Chuan (TCC), often described as "moving meditation," is a traditional Chinese mind-body exercise suitable for individuals of all ages. Mounting evidence demonstrates that TCC can improve physical functions, promote physical activity, and positively impact health and longevity. However, systematic learning is hindered by insufficient teaching resources, difficulties in imparting expertise, and learning environment constraints. TCC auxiliary training systems, an innovative means of human-computer interaction, provide a potential solution. Objective:This scoping review evaluates the research trends and clinical outcomes of TCC auxiliary training systems. Specifically, we compare the development tools, system design, and evaluation or validation processes used by different systems to guide future development in this research area. Methods:Following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines, electronic databases (PubMed, Embase, Scopus, IEEE Xplore, and ACM Digital Library) were systematically searched for studies in English from 2014 to 2024. Two reviewers independently extracted the data and used an adapted version of the Santos evaluation criteria to evaluate the quality of the included studies. The included studies were qualitatively summarized with respect to system design and evaluation verification. Results:Among the 2202 identified studies, 34 studies met the inclusion criteria, of which 24 were rated as medium to high quality. Desktop-based applications dominate the TCC auxiliary training system environment, comprising 38% (13/34) of the selected studies. The hardware and software components of TCC auxiliary training systems vary depending on the development objectives. Regarding system design, 76% (26/34) addressed all groups, with only a minority focusing on specific populations. Interaction design in TCC auxiliary training commonly incorporates human-computer interaction technologies, such as tactile, action, visual, speech, and multimodal interaction. Clinical validation is necessary to implement this system in clinical practice. Most reviewed studies were validated, 6 underwent acceptability validation, 21 underwent feasibility validation, and only 2 virtual reality-based systems underwent clinical efficacy validation, demonstrating their effectiveness in improving cognitive abilities and motor functions in older adults. Conclusions:The TCC auxiliary training system is an innovative health intervention in a rapidly advancing field. This scoping review, the first undertaken on this topic, systematically synthesizes current evidence regarding its design, applications, research trends, and clinical outcomes, thereby establishing a comprehensive foundation to guide and inform future research. However, the current evidence still faces issues such as methodological inconsistencies, insufficient sample diversity, and a lack of long-term effectiveness validation, which limit its generalizability and effectiveness in widespread applications. Future research should place greater emphasis on standardized reporting, applicability to diverse populations, and foster ethical considerations and interdisciplinary collaboration. This will facilitate the widespread deployment of the TCC auxiliary training system and ensure its sustainable integration into the field of health intervention.

BACKGROUND:Amnestic mild cognitive impairment (aMCI) is characterized by marked episodic memory decline. The hippocampus is essential for episodic memory, and integration of information within its subregions is central to this process. This study examined how alterations in hippocampal subregional network relate to episodic memory impairment in aMCI. METHODS:Participants with aMCI (n = 32) were recruited between March 2021 and May 2022, with cognitively normal controls (n = 32) matched for age, sex, and years of education. Episodic memory was evaluated using the Logical Memory subtest of the Wechsler Memory Scale-Revised. Resting-state functional MRI data were acquired. Hippocampal subregional networks were constructed to characterize functional connectivity and topological alterations in aMCI. Pearson correlation analyses were used to assess the relationships between network metrics and episodic memory function. RESULTS:We found impaired integration of the hippocampal subregion network in aMCI, as reflected by increased path length and decreased global efficiency (p < 0.05). Longer path length correlated with lower Logical Memory scores. Functional connectivity decreased between the bilateral parasubiculum and the left granule and molecular layer of the dentate gyrus and between the right parasubiculum and left CA1 (connection-level threshold p < 0.001, network-level threshold pFDR < 0.05). Nodal analyses revealed reduced degree centrality and nodal efficiency in the bilateral parasubiculum and presubiculum (pFDR < 0.05), both positively associated with episodic memory in aMCI (pFDR < 0.05). CONCLUSIONS:These findings suggest that episodic memory impairment in aMCI is linked to altered hippocampal subregional integration, with the parasubiculum and presubiculum as potential key regions.

Age-associated cognitive decline, characterized by progressive memory and executive function impairment without dementia, poses challenges to elderly health. While aerobic exercise and environmental enrichment training may improve cognitive function, the underlying neural mechanisms remain unclear. In this study, we developed a novel intervention combines aerobic exercise (AE) with multisensory stimulation environment training (MSET). This combined training (CT) was more effective in mitigating cognitive decline in aged mice than either individual component or controls, aligning with increased neuronal activity and synaptic plasticity in the hippocampus (HPC) and prefrontal cortex (PFC). Using neural circuit tracing and chemogenetics, we explored the importance of the HPC-PFC circuit. Inhibiting the HPC-PFC circuit reduced the improvement effect of combined training (CT) on cognitive function, whereas activating this circuit enhanced cognitive function. We found candidate molecules responsive to CT in the HPC and PFC using single-cell sequencing. We identified that AE component modulated the expression levels of proprotein convertase subtilisin/kexin type 1 inhibitor (PCSK1N) and lymphocyte antigen 6 family member H (LY6H) in neurons in the HPC and PFC. At the same time, MSET component influenced the expression levels of dipeptidyl peptidase like 6 (DPP6) and glutamate ionotropic receptor NMDA type subunit associated protein 1 (GRINA) in neurons of the HPC and PFC. CT was linked to the upregulation of these molecular targets, which correlated with its beneficial effects. These findings provide insight into the mechanism underlying cognitive improvement associated with CT, suggesting a potential basis for exploring strategies aimed at mitigating cognitive decline through interventions like CT.