While previous research has demonstrated that frailty is associated with increased dementia risk over time, large multi-decade prospective population-based cohort studies remain limited. Furthermore, the association between lower grip strength and blood-based biomarkers of neuropathology and global cognitive function remains under-investigated. We investigated the relationship between varying levels of baseline frailty (measured using a deficit accumulation Frailty Index) and dementia incidence over 17 years, as well as associations of grip strength (hand, pinch and key, assessed at 8- and 14-year follow-up) with blood-based biomarkers of neuropathology (year 8) and with global cognitive function (year 14) in a population-representative cohort of 9,940 mid-to-late life (50-75 years) individuals. In a subsample of 6,357 participants with available dementia information at 17-year follow-up (mean age at baseline [SD], 61.7 [6.6] years; female, 54.3%), 516 received an all-cause dementia diagnosis. Over this time, individuals in the highest frailty index quintile demonstrated a significantly higher risk of all-cause dementia (HR, 1.75; 95% CI, 1.18-2.60) and a vascular dementia diagnosis (HR, 2.44; 95% CI, 1.22-4.91). Cross-sectionally, lower handgrip strength was associated with elevated blood levels of NfL (β=-0.01, p=0.007) and pTau181 (β=-0.004, p=0.017) at 8-year follow-up, as well as poorer cognitive function on the Montreal Cognitive Assessment (MoCA) (β = 0.02, p=0.037) at 14-year follow-up. This study strengthens evidence that frailty is a risk factor for dementia in mid-to-late life. It also suggests that it is of considerable importance to assess frailty and grip strength in individuals 'at risk' of cognitive decline.

On some global implicit function theorems for set-valued inclusions with applications to parametric vector optimization

Cognitive decline is a critical public health concern among older adults. While physical activity (PA) is a recognized modifiable factor for mitigating cognitive deterioration, the specific impact of long-term PA trajectories on the rate of cognitive decline remains understudied, particularly in China. A longitudinal cohort of 3,471 participants aged ≥ 60years from the China Health and Retirement Longitudinal Study (CHARLS) was analyzed. PA trajectories were identified via group-based trajectory modeling (GBTM) on the basis of self-reported PA data from four waves (2011, 2013, 2015, and 2018). Global cognitive function, assessed by episodic memory and mental intactness, was measured repeatedly. Associations between PA trajectories and cognitive decline were analyzed using linear mixed models adjusted for demographic, lifestyle, and health-related factors. Two distinct PA trajectories were identified: a high decreasing trajectory group (43.4%) and a low increasing trajectory group (56.6%). The high decreasing trajectory group initially had higher PA levels but experienced a slight decline, whereas the low increasing trajectory group started with lower PA levels but showed gradual increases. Participants in the high decreasing trajectory group exhibited significantly slower declines in global cognition (β = 0.106, 95% CI: 0.072, 0.140, P < 0.001) and mental intactness (β = 0.116, 95% CI: 0.078, 0.154, P < 0.001) compared to the low increasing trajectory group. Subgroup analysis revealed that participants aged ≥ 75years, females, those with higher education levels, and rural residents experienced slower cognitive decline. Sensitivity analyses confirmed the robustness of these findings. Sustaining higher levels of physical activity over time is associated with a slower rate of cognitive decline in older Chinese adults. This protective effect is especially pronounced in specific demographic subgroups.

Workplace factors across middle and later life may influence cognitive aging and later-life cognitive change. We examined associations of job - education adaptation with global cognitive function (MMSE) in middle-aged and older Korean workers. Using KLoSA (2008-2020), we analyzed 3,322 participants aged ≥45 years employed. Repeated MMSE scores were modeled with generalized estimating equations adjusted for sociodemographic, health, and covariates. Job adaptation was cross-classified with education (≤middle school/high school/≥college). Sensitivity and subgroup analyses by sex and age ( < 65 vs ≥ 65) were performed. Job - education mismatch predicted lower MMSE scores. Compared with Neutral - high school, High-≤middle-school (β = -1.737, 95% CI - 2.669 to -0.804), Low-≤middle-school (β = -1.392, 95% CI - 1.613 to -1.171), and Neutral-≤middle-school (β = -1.227, 95% CI - 1.371 to -1.082) had poorer cognition. Effects were larger in subgroups: females (High-≤middle-school β = -2.357, 95% CI - 3.948 to -0.766), those ≥65 (High-≤middle-school β = -2.144, 95% CI - 3.622 to -0.666), and white-collar (Neutral-≤middle-school β = -2.135, 95% CI - 2.857 to -1.413). Results were robust to sensitivity checks. Job - education mismatch is associated with worse global cognitive function, notably among women, older adults, and some occupational groups. Policies improving person - job fit and skill use may mitigate cognitive decline.

Blood-based biomarkers identify Alzheimer disease and hold promise for monitoring disease progression, even in the preclinical disease stages. To investigate longitudinal trajectories of blood-based biomarkers and association with cognitive decline and risk of progression in individuals with subjective cognitive decline (SCD). This prospective cohort study (Subjective Cognitive Impairment Cohort) of individuals with SCD evaluated at a memory clinic underwent biennial biomarker collection and annual cognitive assessment and diagnostic evaluation from January 1, 2005, to December 31, 2023, with follow-up through 2023. Amyloid status was determined using positron emission tomography or cerebrospinal fluid. Plasma Aβ42/40, phosphorylated tau 217 (pTau217), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) were measured biennially. Cognitive trajectories in memory, attention, language, executive function, and global cognition and clinical progression to mild cognitive impairment or dementia. A total of 298 individuals (mean [SD] age, 61.55 [8.08] years; 174 [58.4%] male) with SCD were included, of whom 80 were amyloid-positive (A+) and 218 were amyloid-negative (A-). Mean (SD) follow-up was 4.8 (2.6) years. Individuals with SCD A+ were older (mean [SD] age, 65.25 [7.14] years; 42 [52.5%] male) than those with SCD A- (mean [SD] age, 60.19 [8.00] years; 132 [60.6%] male). For pTau217, GFAP, and NfL, baseline levels were higher in the A+ group compared with A- group (estimates [SE] amyloid β, 1.11 [0.11], 0.69 [0.13], and 0.36 [0.10], respectively; P < .001 for all). Additionally, these biomarkers showed steeper increases over time in the A+ group than in A- group (estimates [SE] time × amyloid status β, 0.07 [0.02], P < .001; 0.07 [0.02], P < .001; and 0.05 [0.02], P = .005, respectively). Longitudinal increases in pTau217 and GFAP were associated with cognitive decline over time in all domains (β time × biomarker slope = -0.02 to -0.04). Longitudinal decreases in Aβ42/40 and increases in NfL were associated with cognitive decline in global cognition (β = 0.03 [0.01], P = .04) and language (β = 0.04 [0.02], P = .03), and increases in NfL were also associated with decline in global cognition (β = -0.02 [0.01], P = .004), language (β = -0.03 [0.01], P = .007), and executive functioning (β = -0.03 [0.01], P = .02). Steeper pTau217 slope was associated with progression from SCD to mild cognitive impairment or dementia (hazard ratio [HR], 3.6; 95% CI, 1.8-7.4 per 0.05 SD increase per year; C index, 0.89; 95% CI, 0.84-0.93), as were steeper GFAP slope (HR, 1.5 [95% CI, 1.0-2.2]; C index, 0.81 [95% CI, 0.73-0.88]) and steeper NfL slope (HR, 2.6 [95% CI, 1.3-5.2]; C index, 0.77 [95% CI, 0.69-0.85]). Aβ42/40 slope was not associated with progression. This cohort study of individuals with SCD suggests that longitudinal plasma pTau217 and GFAP are suitable biomarkers for monitoring AD pathology. Their changes were associated with cognitive decline and clinical progression, supporting their potential utility for early intervention and disease monitoring.

Let G G be a finite abelian p p -group. We count étale G G -extensions of global rational function fields F q ( T ) \mathbb F_q(T) of characteristic p p by the degree of what we call their Artin–Schreier conductor. The corresponding (ordinary) generating function turns out to be rational. This gives an exact answer to the counting problem, and seems to beg for a geometric interpretation. This is in contrast with the generating functions for the ordinary conductor (from class field theory) and the discriminant, which in general have no meromorphic continuation to the entire complex plane.

BackgroundIn order to elucidate the neuromodulatory mechanisms underlying therapeutic subthalamic deep brain stimulation (DBS), we here reverse-translate a methodological pipeline that integrates neurostimulation effect parameterization and molecular imaging.Methods18F-fluorodeoxyglucose positron emission tomography was performed in a human-mimicking A53T alpha-synuclein Parkinson’s disease rat model and in control rats under both stimulation ON and OFF conditions, with additional CT scans acquired for each rat. Patient-derived approaches—including electrode modeling, electric field estimation, and volume of tissue activated measurement—were applied to assess stimulation effects at the stimulation spot.ResultsWe revealed consistent hypometabolism in the ipsilateral subthalamic nucleus, substantia nigra, zona incerta, cerebellum, and entopeduncular nucleus, alongside hypermetabolism in the ipsilateral lateral caudate putamen and globus pallidus externus in A53T rats at the OFF condition. Subthalamic DBS improved motor dysfunction and induced specific metabolic responses that differentiated from controls, including increased metabolism in the ipsilateral subthalamic nucleus, substantia nigra, and zona incerta, and decreased metabolism in the bilateral primary motor and somatosensory area, lateral caudate putamen, and contralateral secondary motor area.ConclusionsTherapeutic subthalamic DBS activates the target region and modulates global brain function by restoring OFF-state hypometabolism in the ipsilateral subthalamic–substantia nigra loop and by reducing metabolic activity in the bilateral cortico-striatal circuitry. A reverse-translational pipeline is established to study stimulation-induced modulation of brain function, integrating a novel positron emission tomography template aligned with the Waxholm space of Sprague–Dawley rats.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40035-025-00523-3.

The interaction between vehicles moving on a continuous elastic medium and underlying support layers generates induced vibrations that may affect surrounding structures. In environmental impact studies for proposed and planned new railway lines, it is frequently necessary to characterize vibration intensities for different track support structural packages. For train systems, in addition to the mechanical properties of the foundation package, both rail roughness and wheel roughness (flat- wheel conditions) become particularly relevant. This work develops a modeling approach for parametric analysis of such systems, employing a matrix assembly methodology in generalized coordinates along with global interpolation functions for the rail (modeled as a constant-section Euler-Bernoulli beam) and discrete coordinates to represent sleeper kinematics and elastic support medium deformation. Rail deformation is approximated through superposition of a Fourier basis with interpolation functions accounting for rigid body displacements of the rail. The implementation of global interpolation functions and the orthogonality properties of the rail deformation interpolation functions enable efficient assembly of the system’s motion equations matrices (some being time-variant) for the coupled vehicle-track model incorporating rail, sleepers, and elastic foundation support. Through numerical integration of the linear time-variant model, rail vibrations are analyzed under the assumption of rigid wheel-rail contact. Results from this primary model are compared with a mass-mass coupling model using a time-domain metric.

Exploring psychological resilience as a mediator between frailty and health-related quality of life among older cancer survivors: a cross-sectional study.

Associations of metabolic obesity phenotypes with cognitive aging in middle-aged and elderly Chinese adults.

The aim of this umbrella review is to assess the effectiveness of exercise interventions in preventing and managing cancer-related cognitive impairment among cancer survivors, providing an evidence-based foundation for clinical practice. The umbrella review was preregistered on PROSPERO. It included systematic reviews that assessed any exercise interventions aimed at improving cognition in cancer patients. The overview adhered to gold standard guidelines and recommendations. We utilized AMSTAR 2 to evaluate the quality of the literature and to synthesize the consistency of the evidence in order to formulate recommendations. Based on 28 systematic reviews, four subtypes of exercise interventions were identified. High-quality evidence consistently demonstrates that aerobic exercise significantly improves performance on specific neuropsychological tests. The Hopkins Verbal Learning Test shows a score improvement (standardized mean difference (SMD) = 0.65, 95% confidence interval (CI) = 0.42, 0.88); The Trail Making Test Part A shows a reduction (SMD = -0.61, 95% CI = -0.92, -0.30). Mind-body exercises also have notable effects on alleviating subjective cognitive complaints, indicated by an improvement in the Functional Assessment of Cancer Therapy-Cognitive Function score (SMD = 0.82, 95% CI = 0.49, 1.15). However, the evidence for objective cognitive improvement is limited and inconsistent. Combined training presents preliminary evidence of synergistic effects in enhancing global cognitive function, with an average effect across multiple cognitive domains (SMD = 0.45, 95% CI = 0.20, 0.70). Currently, resistance training lacks robust, high-quality evidence, and more studies are needed to determine its effects on specific objective cognitive domains. This review highlights exercise intervention as a key nonpharmacological approach for managing Cancer-Related Cognitive Impairment. Urgent priorities for future research include the following: (1) conducting high-quality randomized controlled trials to validate exercise tolerability in patients undergoing active treatment; (2) developing multimodal assessment frameworks that integrate neuroimaging and blood-based biomarkers; and (3) establishing personalized exercise guidelines tailored to specific cancer types and treatment phases. Additionally, future studies should focus on clarifying the biological mechanisms that underpin the cognitive improvements associated with exercise. This will help create a stronger evidence base for precision exercise prescription.

Background: Acquired brain injury (ABI) leads to cognitive, emotional, and social impairments that substantially affect quality of life. Although cortical lesions have traditionally received more attention, increasing evidence highlights the importance of the integrity of major white matter association tracts. However, few studies have simultaneously examined cognitive, affective, and social domains within a tractography framework. Methods: In this exploratory pilot study, ten ABI patients underwent diffusion-based tractography of the principal association tracts—the superior and inferior longitudinal fasciculi, the uncinate fasciculus, the inferior fronto-occipital fasciculus, and the cingulum—together with a comprehensive neuropsychological battery covering global cognition, executive functions, memory, emotional symptoms, and empathy. Results: Marked interindividual variability was observed in both tract profiles and neuropsychological outcomes. Findings revealed paradoxical associations, such as larger volumes of the left superior longitudinal fasciculus being linked to poorer cognitive performance, suggesting maladaptive reorganization. Hemispheric lateralization patterns were also identified, with the uncinate fasciculus showing differential contributions to immediate memory and working memory across hemispheres. Notably, empathy scores consistently correlated with volumes of the inferior longitudinal fasciculus, the uncinate fasciculus, and the cingulum, in line with recent evidence on the structural basis of socio-emotional outcomes after ABI. Conclusions: Although limited by sample size, this study provides novel evidence regarding the structure–function paradox, hemispheric specialization, and the clinical relevance of empathy in ABI. Overall, the results support the integration of tractography of the main association tracts with neuropsychological assessment as complementary tools to advance personalized neurorehabilitation.

Alzheimer disease (AD) is characterized by dysregulated gamma brain oscillations. Transcranial alternating current stimulation (tACS) is a novel, noninvasive brain stimulation technique capable of entraining cerebral oscillations at targeted frequencies. To assess the safety, feasibility, and efficacy of home-based gamma tACS applied over the precuneus in patients with prodromal and mild AD. This double-blind, randomized, sham-controlled clinical trial with an open-label extension phase was conducted at a tertiary AD research clinic in Italy from December 10, 2022, to October 15, 2024. Patients with a diagnosis of AD were eligible to participate. Participants were randomized to receive either home-based gamma tACS (5 sessions/wk, 60 minutes each) or sham stimulation for 8 weeks (double-blind phase). All participants subsequently received gamma tACS for an additional 8 weeks (open-label phase) and an 8-week follow-up. The primary end points were safety, feasibility, and clinical efficacy. Secondary end points included measures of biological efficacy, including gamma band power via electroencephalography, cholinergic neurotransmission, AD plasma biomarker levels, and brain connectivity as assessed via magnetic resonance imaging. Sixty consecutive patients with prodromal or mild AD were screened; 50 were randomized to gamma or sham tACS (mean [SD] age, 67.3 [7.8] years; 25 [50.0%] female and 25 [50.0%] male). Home-based gamma tACS was safe and well-tolerated. A significant enhancement in global cognitive functions, activities of daily living, and associative memory performances was observed. Marginal mean differences between the sham vs gamma tACS groups were significant for the Clinical Dementia Rating sum of boxes (0.35; 95% CI, 0.10-0.61; P = .007), Alzheimer Disease Assessment Scale-cognitive subscale (0.93; 95% CI, 0.50-1.36; P = .001), Alzheimer Disease Cooperative Study-Activities of Daily Living (-0.55; 95% CI, -0.89 to -0.21; P = .02), and Face-Name Association Test (-1.14; 95% CI, -1.66 to -0.61; P ≤ .001). During the open-label phase, a significant marginal mean difference was observed for Alzheimer Disease Assessment Scale-cognitive subscale (-0.59; 95% CI, -1.02 to -0.16; P = .007), Alzheimer Disease Cooperative Study-Activities of Daily Living (0.41; 95% CI, 0.04-0.08; P = .02), and Face-Name Association Test (1.04; 95% CI, 0.50-1.57; P = .003). Neurophysiological measures showed an increase in cholinergic transmission, coinciding with an increase in gamma power following gamma tACS, effects not seen with sham stimulation. No changes of plasma biomarkers were observed. No add-on effect was observed after 2 repeated treatments with gamma tACS, suggesting that 8 rather than 16 weeks of treatment represents the ideal duration. In this randomized clinical trial, home-based gamma tACS was feasible and improved clinical outcomes in AD, with neurophysiological evidence of brain engagement. These findings support further investigation of gamma tACS as a potential therapeutic intervention for AD. ClinicalTrials.gov Identifier: NCT05643326.

The association of cognitive functions with functional outcomes during post-stroke recovery: A cross-sectional study.

Asymmetric window detection of abrupt global drought-wetness alternations and ecological responses.

The aims of this study were to determine 1) whether organizational and non-organizational religious participation are associated with cognitive function trajectories among older African Americans and 2) whether the associations between religious participation and cognitive function trajectories vary by age. Data for this study come from the Minority Aging Research Study (N = 822). Organizational religious participation included service attendance, and non-organizational religious participation included religious coping and prayer/meditation. We utilized group-based trajectory modeling to identify cognitive function trajectories based on global cognitive function scores. We identified four distinct cognitive trajectories: fast decline, slow decline, moderate and stable, and high and stable. While prayer/meditation was associated with membership in the moderate-and-stable trajectory, significant interactions between the non-organizational religious participation variables and age indicated that the associations between non-organizational religious participation and cognitive trajectory varied by age. Neither religious coping nor service attendance was associated with cognitive trajectories. These findings illustrate substantial heterogeneity in cognitive aging among older African Americans. Non-organizational religious participation primarily served as a preventive factor among younger participants but functioned more prominently as a coping resource among the oldest participants. These age-related distinctions emphasize the diverse ways in which religiosity could foster cognitive resilience or aid in navigating cognitive decline among older African Americans.

Role of Liver Function Assessment in Portal Venous Interventions and Locoregional Therapies for Liver Tumors.

Health-related quality of life and related factors among esophageal cancer survivors after esophagectomy in the 6-month postoperative period: A multicenter cross-sectional study in north China.

Background EEG grading for the assessment of neonatal encephalopathy in full term neonates.

Assessing spatial differences of perceptions of cultural ecosystem services for coastal cultural landscape management: A case study from rural and urban areas in Quanzhou, China.