Non-pharmacological interventions (NPIs) have been widely applied to address age-related cognitive decline. However, practical challenges of implementing NPIs in older adults have limited the availability of open datasets that concurrently capture multiple, heterogeneous intervention modalities within a single resource. Existing studies are thus fragmented, relying on single-intervention designs and relatively small cohorts, which constrains cross-study comparison and data reuse. Here, we present an open database derived from three independently registered NPIs trials conducted in community-dwelling adults (training/control group: N = 96/47; Chinese Clinical Trial Registry; 53–80 years). The training group received structured NPIs over 6–16 weeks encompassing multiple intervention modalities, including square dance, video game, aerobic exercise, combined, or multimodal programs. Control participants engaged in protocol-matched activities, such as stretching exercise, maintenance of baseline lifestyle, or health lectures. All participants completed standardized neuropsychological assessments and structural MRI/resting-state functional MRI scans at pre- and post-intervention time points. This database provides an openly accessible, well-characterized resource to support data discovery, reuse, and integrative analyses of non-pharmacological interventions in older adults.

Menopausal hormone therapy (MHT) has long been hypothesized to support women's brain health through estrogen-related neurotrophic and metabolic mechanisms. However, structural MRI studies examining MHT-associated brain changes have produced strikingly inconsistent findings, ranging from apparent neuroprotection to accelerated structural decline. To clarify the sources of this heterogeneity, we conducted a systematic review of 24 structural MRI studies identified from PubMed, Web of Science, and EBSCO (search through June 2025), synthesizing evidence across global morphometric analyses, region-of-interest investigations, and brain structure-specific metrics. Across whole-brain analyses, most studies reported larger gray matter volumes in frontal and temporal regions among MHT users. In contrast, region-specific and metric-based studies yielded mixed results. Importantly, negative structural outcomes-such as reduced hippocampal volume or increased white matter hyperintensities-were consistently confined to studies in which MHT was initiated long after menopause or administered as oral conjugated equine estrogens. In studies that explicitly accounted for initiation timing or examined transdermal estradiol, structural findings were predominantly neutral or regionally specific and positive, rather than globally adverse. These converging patterns suggest that the apparent inconsistency in the literature does not reflect a uniform lack of MHT effects on the brain, but rather systematic modulation by two underappreciated factors: the neurobiological timing of intervention and the pharmacokinetic properties of hormone delivery. In addition, the widespread reliance on conventional structural MRI measures-particularly hippocampal volume-may limit sensitivity to subtle, early estrogen-related neural changes. We propose that future research prioritize longitudinal randomized controlled designs, integrate timing- and formulation-specific analyses, and adopt more sensitive neuroimaging markers, including cortical thickness, entorhinal cortex metrics, and multimodal MRI approaches. Such efforts are essential for resolving longstanding controversies and for determining whether, and under what conditions, MHT may support brain health across the menopausal transition.

Loneliness, a distressing subjective experience that may become a chronic psychosocial stress exposure when persistent, has been linked to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, yet empirical findings linking loneliness to cortisol regulation remain inconsistent. One largely unexplored possibility is that loneliness may exert non-linear association on HPA-axis activity. This study examined the curvilinear association between loneliness and hair cortisol concentration (HCC) in community-dwelling older adults. Participants were 126 older adults aged ≥60 years at elevated cardiovascular risk, drawn from the baseline assessment of a randomized controlled trial in China. Loneliness was assessed using the 6-item De Jong Gierveld Loneliness Scale. HCC was quantified using liquid chromatography-tandem mass spectrometry. Linear regression models tested quadratic associations between loneliness and log-transformed HCC, adjusting for demographic, methodological, psychological, social, and health-related covariates. Loneliness showed a significant curvilinear association with HCC, with HCC appearing higher at low-to-moderate loneliness and lower at higher loneliness. The quadratic term remained significant after full covariate adjustment, but sensitivity analyses indicated that statistical significance was sensitive to the exclusion of high-influence cases. These preliminary findings suggest that loneliness may be nonlinearly associated with long-term cortisol output among older adults at elevated cardiovascular risk. The findings may help contextualize prior inconsistencies in the loneliness-cortisol literature and highlight the need for longitudinal studies to clarify temporal and mechanistic pathways.

BACKGROUND:This study aimed to explore the potential relationship between resting-state brain network attributes and adolescent major depressive disorder (MDD), with a focus on understanding how resting-state electroencephalogram (EEG) network features correlate with Hamilton Depression Rating Scale (HAMD) scores, and to identify potential physiological biomarkers for predicting HAMD scores in adolescents with MDD. METHODS:Adolescent MDD presents unique neurodevelopmental challenges, yet the neurophysiological correlates of symptom severity remain poorly characterized. This study investigated resting-state EEG network topology and its relationship with HAMD scores in adolescent MDD, aiming to identify potential neural biomarkers for depression severity. RESULTS:MDD patients exhibited significantly enhanced frontal-parietal connectivity compared with healthy controls (HC) (p < 0.05, false discovery rate (FDR)-corrected). HAMD scores correlated positively with coefficient (Clu) (r = 0.401), global efficiency (Ge) (r = 0.408), and local efficiency (Le) (r = 0.402), while showing a negative correlation with characteristic path length (Cpl) (r = -0.408; all PFDR < 0.05). The regression model achieved strong prediction accuracy (R2 = 0.38, p < 0.001; root mean square error (RMSE) = 2.83), and network features distinguished MDD from HC with 94% classification accuracy. CONCLUSION:These preliminary findings deepen our understanding of adolescents with MDD and suggest that resting-state brain network attributes in the alpha band may serve as a potential physiological biomarker for predicting HAMD scores.

Non-pharmacological interventions (NPIs) in aging neuroscience have largely focused on intervention-specific regional effects, with limited understanding of generalizable network-level mechanisms. Here, adopting a previously unexplored gradient-based perspective of functional brain organization, we analyzed an NPI dataset involving four interventions in older adults (training/control group: n = 112/59). NPIs led to strengthened intra-network functional integration and maintained macroscale gradient architecture. Virtual lesion analyses identified the dorsal attention network (DAN) as a key contributor to gradient maintenance. Critically, enhanced post-intervention DAN connectivity was associated with maintained gradient structure and improved global cognition. These findings establish a unifying framework in which the DAN acts as a convergent hub through which diverse NPIs preserve functional brain organization and attenuate cognitive aging. ### Competing Interest Statement The authors have declared no competing interest.

Neuropathic pain associated with central sensitization is common in diabetic patients, but the underlying mechanisms remain unclear. Here, a proteomics screen identified a previously uncharacterized protein, galectin-related protein (LGALSL), which was significantly upregulated in cerebrospinal fluid and extracellular fluid of the anterior cingulate cortex (ACC) in diabetes-related neuropathic pain (DNP) model rats. Exogenous LGALSL administration reduced mechanical nociceptive thresholds by activating glutamatergic neurons in the ACC (ACCGlu). Chemogenetic manipulations and functional assays revealed that neuron-derived LGALSL directly binds to vimentin on ACC astrocytes, activating those astrocytes. These activated astrocytes subsequently maintain ACCGlu hypersensitivity, driving mechanical hypersensitivity in diabetic rats. Blocking LGALSL-vimentin interactions with a synthetic peptide alleviated LGALSL-induced mechanical hypersensitivity. This study establishes LGALSL-dependent astrocyte-mediated hyperactivation of ACCGlu neurons as a new pathological mechanism of neuropathic pain in diabetes.

Evidence suggests that cognitive impairments due to obstructive sleep apnea (OSA) are related to abnormal lipid metabolism. Abnormal lipid metabolism in the brain might be a potential cause of neurodegeneration. Nonetheless, there is limited clarity regarding the comprehensive lipid metabolism changes in the hippocampus induced by chronic intermittent hypoxia (CIH). Targeted lipidomic analysis of mouse hippocampus and HT22 cells was essential to exploring changes in lipid metabolism after CIH exposure. The approach was used to quantify 575 lipid species in mouse hippocampus and 1285 lipid species in HT22 cells, belonging to 6 different classes. Among those lipid classes, glycerophospholipids (GP), fatty acyls (FA), sphingolipids (SP), glycerolipid (GL), and prenol lipids (PR) were not significantly changed in mouse hippocampus under CIH conditions, but steroid (ST) levels were significantly reduced. Based on in vitro results, CIH exposure significantly raises the levels of several lipids, including GP, PR, SP, and ST. However, GL and FA did not change significantly. Notably, in vivo as well as in vitro experiments showed down-regulation of LPI (16:0), LPI (18:0), PC (18:1/20:4), PE (O-18:0/16:0), PE (O-16:0/22:6), PI (18:0/18:0), and up-regulation of PI (18:0/19:2). Additionally, in CIH conditions, lipid droplets (LDs) typically accumulate as a result of metabolism disorders. Disorders of lipid metabolism and the abnormal accumulation of LDs in neurons cause neuronal damage and behavioral disorders. The altered levels of LPI, PC, PE, and PI in OSA patients might provide new insights into understanding lipid metabolism disorders in the nervous system.

Children and adolescents with type 1 diabetes (T1D) experience persistent impacts on quality of life (QoL). While most previous studies have relied on cross-sectional designs, this prospective cohort study intended to: (1) assess longitudinal changes in patient-reported QoL over a three-year period; (2) identify distinct QoL trajectory subgroups; and (3) examine demographic, physiological, psychological, and clinical determinants associated with trajectory membership and multidimensional QoL outcomes. Two hundred children and adolescents with T1D from China were followed for three years in a longitudinal cohort study. QoL was measured using the Quality of Life Scale for Children and Adolescents (QLSCA) at baseline from June 2019 to May 2020, with follow-up visits at years 1, 2, and 3 thereafter. Trajectories of QoL and associations with determinants were identified via iterative estimations of group-based trajectory models and multivariable multinomial logistic regression, respectively. The specific impacts of the determinants on QoL were revealed using multiple linear regressions. Changes in QoL dimensions over time were examined using linear mixed models, while changes in determinants were analyzed using both linear mixed models and generalized estimating equations. Four QoL trajectory groups were identified (N = 200): poor (19.5

This study explored the feasibility and preliminary impact of combining positive psychology and lifestyle interventions on cardiovascular health among older adults. A mixed-methods study with a pre-test/post-test design was conducted. Thirteen participants with medium to high cardiovascular risk and at least two modifiable risk factors attended five in-person group sessions over two weeks. For the primary outcome, adherence was assessed through session attendance and homework completion, while acceptability was evaluated across five dimensions: overall satisfaction, training procedure, assessment, implementation generalizability, and suggestions for improvement. Secondary outcomes examined effects on physical health, psychological well-being, and health behaviors. The results showed high adherence, with all participants attending five sessions and most completing homework. For acceptability, quantitative ratings showed good results, and qualitative results indicated enhancement in positive emotions, self-perceptions, physical health, and health literacy. Self-reported health status and dietary habits showed improvements. The findings suggested potential for broad implementation.

Depression presents sexual dimorphism, and one important factor that increases the frequency of depression and contributes to sex-specific variations in its presentation is obesity. The conventional use of Body Mass Index (BMI) as an indicator of obesity is inherently limited due to its inability to distinguish between fat and lean mass, which limits its predictive utility for depression risk. Implementation of dual-energy X-ray absorptiometry (DXA) investigated sex-specific associations between body composition (fat mass, appendicular lean mass) and depression. Data from the NHANES cycles between 2011 and 2018 were analyzed, including 3,637 participants (1,788 males and 1,849 females). Four body composition profiles were identified in the subjects: low adiposity-low muscle (LA-LM), low adiposity-high muscle (LA-HM), high adiposity-low muscle (HA-LM) and high adiposity-high muscle (HA-HM). After accounting for confounding variables, the associations between fat mass index (FMI), appendicular skeletal muscle mass index (ASMI), body fat percentage (BFP), body composition phenotypes, and depression risk were assessed using restricted cubic spline (RCS) curves and multivariable logistic regression models. We further conducted interaction analyses for ASMI and FMI in females. RCS curves indicated a U-shaped relationship between ASMI and the risk of depression in males. Logistic regression analysis revealed that in males, the second (OR = 0.43, 95

This review presents the advancements in research on risk prediction models for physical restraint among the elderly. As the global population ages, the issue of physical restraint in older adults has become increasingly prominent, making accurate risk prediction essential for enhancing their quality of life. Current Status: Physical restraint rates exhibit marked regional disparities (e.g., 84.9% in Spain vs. 1.9% in the US). Key risk factors include age ≥75, dementia, and agitation. Machine learning models achieve higher accuracy than traditional statistical approaches, but hybrid models better balance precision and interpretability. Future Directions: (1) Developing real‐time monitoring systems via sensor technology; (2) Establishing ethical frameworks for model deployment through clinician-data scientist partnerships; (3) Implementing validated tools in clinical settings to minimize restraint use. Finally, the review emphasizing the need for improved methodologies and the integration of interdisciplinary approaches to better address this complex issue.

The neural mechanisms underlying sex-specific pain, in which males and females exhibit distinct responses to pain, remain poorly understood. Here we show that in a mouse model of male-specific pain hypersensitivity response to pain conditioning environments (contextual pain hypersensitivity model), elevated free-testosterone leads to hyperactivity of glutamatergic neurons in the medial preoptic area (GlumPOA) through activation of androgen receptor signaling, which in turn induces contextual pain hypersensitivity in male mice. Although not observed in naïve female mice, this pain phenotype could be induced in females via chronic administration of testosterone propionate. In addition, GlumPOA neurons send excitatory inputs to GABAergic neurons in the ventrolateral periaqueductal gray (GABAvlPAG) that are required for contextual pain hypersensitivity. Our study thus demonstrates that testosterone/androgen receptor signaling enhances GlumPOA → GABAvlPAG pathway activity, which drives a male-specific contextual pain hypersensitivity, providing insight into the basis of sexually dimorphic pain response.

Conditioned fear learning enables an organism to use sensory cues to predict potential threats and take adaptive responses to avoid bodily harm. The generalization of fear to safety situations is a common cognitive disorder after traumatic stress. The current study investigated the effect of nerve injury on the fear memory in the mice of both sexes, and found that the neuropathic pain correlated with the contextual fear generalization, a maladaptive fear response to non-threatening environments. Our data showed that Ras and Rab interactor 1 (RIN1), a neuron-specific protein in the brain, was critically involved in the modification of fear memory. Peripheral nerve injury reduced the expression of RIN1 in the dorsal CA1 pyramidal neurons, which led to an enhanced synaptic distribution of N-methyl-D-aspartate (NMDA) subtype glutamate receptors containing GluN2B subunit (GluN2B receptors). Microinjection of GluN2B receptor-selective antagonist ifenprodil into the dorsal CA1 region attenuated the generalized contextual fear without significant influence on the auditory fear memory. Targeted knockdown of RIN1 in the dorsal CA1 pyramidal neurons mimicked the nerve injury by inducing the GluN2B receptor-dependent generalization of contextual fear. These data implicated the contextual fear generalization as one of the anxiety-related disorders during neuropathic pain and indicated an important role of RIN1 in the negative control over the generalized fear.

ObjectiveThis study used latent profile analysis to identify distinct profiles of rehabilitation motivation among Chinese patients with stroke and explored the multidimensional predictors of rehabilitation motivation across different patient subgroups based on the biopsychosocial medical model.MethodsFrom September 2024 to January 2025, 328 patients with stroke were recruited from the rehabilitation departments of three tertiary hospitals in China using convenience sampling. Data collection included (1) a general information questionnaire, (2) Chinese version of the Stroke Rehabilitation Motivation Scale, (3) Modified Barthel Index, (4) the National Institutes of Health Stroke Scale, and (5) Kessler Psychological Distress Scale. Data were analyzed using Mplus version 8.3 and SPSS version 27.0.ResultsThree latent classes of rehabilitation motivation were identified among patients with stroke: (1) Low Rehabilitation Motivation-Intrinsic Drive Deficiency (Class 1, 30.2%), (2) Moderate Rehabilitation Motivation-Extrinsic Drive Stability (Class 2, 39.0%), and (3) High Rehabilitation Motivation-Intrinsic Drive Sufficiency (Class 3, 30.8%). Multiple logistic regression indicated that age, monthly household income, ADL, severity of neurological impairment, and psychological distress were significant predictors of different rehabilitation motivation classes.ConclusionThis study identified significant heterogeneity in the rehabilitation motivation profiles of patients with stroke. Healthcare professionals should implement targeted interventions based on the distinct motivational profiles of patients with stroke during their rehabilitation process, with the aim of effectively mobilizing their intrinsic motivation to participate in rehabilitation therapy.

Pain in one part of the body profoundly diminishes the sensation of pain in other parts of the body in humans. Here, we found that pain-related behaviors in hindpaw are inhibited by noxious stimuli from diverse body regions in mice. Using activity-dependent cell labeling in male FosTRAP2 mice, we captured a neuronal ensemble in the layers 2-4 of secondary somatosensory cortex (S2) that was activated during pain at diverse body regions induced analgesia. Single-cell projection analysis showed that these S2 neurons receive projections from the contralateral S2 and specifically innervate the layer 4 of primary somatosensory cortex (S1). Microendoscopic calcium imaging and chemogenetic manipulation in freely moving mice showed that this S2 -> S1 feedforward inhibitory circuit mediates ipsilateral pain-induced analgesia, whereas contralateral S2 innervation of the S2 -> S1 circuit mediates contralateral pain-induced analgesia. Our study defines the intra-somatosensory cortical circuits underlying "pain inhibiting pain", expanding the scope of known circuit mechanisms involved in pain relief.

The study aimed to examine the association between smartphone usage and cognitive function among older adults in Beijing, China. A cross-sectional study was conducted on 209 older adults aged 60 years and above in Beijing in 2023. This study was divided into two parts: a face-to-face questionnaire and objective data collection on smartphone usage. Multiple linear regression was used to identify predictors of cognitive function. Results showed that education level, marital status, and years of smartphone use were significant predictors of cognitive function. Besides, apart from social applications, there was a positive correlation between smartphone usage and cognitive function. Therefore, it is advisable to encourage older adults to start using smartphones across various categories, with particular emphasis on non-social applications.

OBJECTIVE:To compare the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) under facial feature point (FFP) localization versus neuro-navigated localization for depression. METHODS:42 depressed patients were randomly assigned to two groups, received 10 Hz rTMS twice daily for 10 consecutive days. Relevant symptom scale assessments were conducted by professionals at baseline, after 10 sessions, and at the end of treatment. The confidence interval was calculated at a 95 % confidence level. The significant level was set at p < 0.05. RESULTS:The absolute change in Hamilton Rating Scale for Depression (HAMD) total score from baseline to the end of therapy did not differ significantly between the groups. The generalized estimating equation showed the main effect of time was significant, which showed improvement of depressive symptoms in patients throughout treatment. Upon completion of the treatment, FFP group showed a response rate of 64.7 % and a remission rate of 29.4 %, whereas the navigated group exhibited a response rate of 61.1 % and a remission rate of 44.4 %. There was no serious adverse events occurred during the treatment process. Throughout the study, no intervention was made on the normal medication treatment, and some patients had concomitant antidepressants and benzodiazepines. CONCLUSION:There was no significant difference in clinical efficacy between FFP localization and navigated localization in the small-sample study. However, due to the limited sample size and lack of rigorous non-inferiority testing, the superiority of one over the other remains uncertain, necessitating rigorous experimental design to validate the efficacy difference between the two localization methods.

Cardiovascular disease (CVD) remains a major public health challenge in China, and dietary factors play a crucial role in its development. Understanding the trends and key dietary risk factors of diet-related CVD is essential for formulating effective prevention and control strategies. This study utilized data from the Global Burden of Disease (GBD) 2021 to conduct a comprehensive analysis of dietary risk factors associated with CVD in China over the period from 1990 to 2021. The analysis focused on various dietary components and their relationships with CVD-related mortality and disability-adjusted life years (DALYs). In 2021, the age-standardized mortality rate (ASMR) for diet-related CVD was 77.76 per 100,000 population, and the age-standardized DALY rate (ASDR) was 1,499.58 per 100,000 population. A diet high in sodium continued to be the leading dietary risk factor. Notably, diets high in processed meat, low in polyunsaturated fatty acids, low in whole grains, and high in sugar-sweetened beverages showed upward trends. Among these, the death and DALY rates associated with high sugar-sweetened beverage consumption demonstrated the most significant growth. The findings highlight the urgent need to implement ongoing preventive measures. Prioritizing strategies to reduce sodium intake, increase whole grain and fruit consumption, and limit the intake of processed meats and sugary beverages is crucial for mitigating the burden of CVD in China. Healthcare practitioners and policymakers can use these insights to develop targeted interventions and public health policies.

Background:As the population in China rapidly ages, the prevalence of mild cognitive impairment (MCI) is increasing considerably. However, the causes of MCI vary. The continued lack of understanding of the various subtypes of MCI impedes the implementation of effective measures to reduce the risk of advancing to more severe cognitive diseases. Aims:To estimate the prevalence and incidence rates of two MCI subtypes-amnestic MCI (aMCI) and vascular cognitive impairment without dementia (VCIND)-and to determine modifiable factors for them among older individuals in a multiregional Chinese cohort. Method:This 1-year longitudinal study surveyed a random sample of participants aged≥60 years from a large, community-dwelling cohort in China. Baseline lifestyle data were self-reported, while vascular and comorbid conditions were obtained from medical records and physical examinations. In total, 3514 and 2051 individuals completed the baseline and 1-year follow-up assessments, respectively. Logistic and linear regression analyses were used to identify the modifiable factors for MCI subtypes and predictors of cognitive decline, respectively. Results:Among our participants, aMCI and VCIND demonstrated prevalence of 14.83% and 2.71%, respectively, and annual incidence (per 1000 person-years) of 69.6 and 10.6, respectively. The risk factor for aMCI was age, whereas its protective factors were high education level, tea consumption and physical activity. Moreover, VCIND risk factors were age, hypertension and depression. The presence of endocrine disease, cerebral trauma or hypertension was associated with a faster decline in cognition over 1 year. Conclusions:MCI is a serious health problem in China that will only worsen as the population ages if no widespread interventions are implemented. Preventive strategies that promote brain activity and support healthy lifestyle choices are required. We identified modifiable factors for MCI in older individuals. The easy-to-adopt solutions such as tea consumption and physical activity can aid in preventing MCI. Trial registration number:NCT03672448.