Computerized, self-adaptive cognitive training has emerged as a promising digital therapeutic for cognitive impairment; however, its underlying training mechanisms in schizophrenia remain poorly understood. This double-blind, randomized trial compared self-adaptive difficulty (SAD) with fixed-difficulty (FD) computerized cognitive training program, evaluating both domain-specific cognitive and clinical outcomes, and exploring difficulty-performance coupling as a potential active therapeutic mechanism. Seventy-two patients with schizophrenia (SAD = 41, FD = 31) completed 4 weeks of training, and 40 patients (n = 20 per group) were assessed at week 8. Cognitive outcomes were measured using the Cognitive Index (CI) and MATRICS Consensus Cognitive Battery (MCCB), while clinical symptoms were also assessed. Linear mixed-effects models (LMMs) revealed significantly greater and faster cognitive improvements in the SAD compared with the FD group in attention and agility, with faster improvement also observed in thinking. Robust difficulty-performance coupling was observed across all cognitive domains. Additionally, positive symptoms improved significantly in the SAD group compared to the FD group at week 4. Self-adaptive cognitive training enhances and accelerates cognitive improvements in schizophrenia, particularly in attention and processing speed, and also benefits positive symptoms. Difficulty-performance coupling may reflect dynamic load calibration as a key therapeutic mechanism in digital cognitive training. Trial registration: Chictr.org.cn, number, ChiCTR2000040326, registered 2020-11-27.
Type 2 diabetes (T2DM) heightens cognitive impairment risk, yet the mechanisms remain unclear. Hyperglycemia-induced iron dysregulation in deep gray matter (DGM) nuclei may be a crucial mechanism. To investigate DGM iron deposition in T2DM using Quantitative Susceptibility Mapping (QSM) and determine its association with cognitive function. Prospective. One hundred and fifteen T2DM patients (59.13% male, 53.04 ± 10.12 years) and 176 healthy controls (29.55% male, 50.18 ± 9.41 years). 3 T; 3D T1-weighted and 3D multi-echo gradient-echo sequences. The magnetic susceptibility of eight bilateral DGM nuclei was quantitatively assessed via QSM. Comprehensive evaluations were conducted for all participants, covering demographic and clinical characteristics, and a battery of multidimensional neuropsychological tests. Group differences in DGM magnetic susceptibility were assessed using two-sample t-tests. Partial correlation and multiple linear regression analyses were performed to examine associations between regional susceptibility and both cognitive and clinical variables. Mediation and moderation analyses were conducted to examine the relationships between various clinical factors, DGM susceptibility, and cognitive function. A corrected p < 0.05 was considered statistically significant. T2DM patients showed significantly increased magnetic susceptibility in the thalamus, putamen, substantia nigra, and right red nucleus, while the caudate nucleus showed reduced susceptibility. Iron content in the caudate nucleus positively correlated with MoCA (r = 0.193) and CDT (r = 0.196), whereas putamen iron deposition negatively correlated with AVLT-immediate (r = -0.211) and AVLT-delay (r = -0.187) and positively correlated with GPT-L (r = 0.22). Substantia nigra susceptibility partially mediated the effect of age on MoCA scores (β = -0.008), and diabetes status moderated the age-related rate of iron accumulation in the substantia nigra (interaction coefficient = 0.770). Age, diabetic status, sex, and BMI were significant factors influencing brain iron deposition. Dysregulated brain iron metabolism in T2DM is associated with cognitive dysfunction. Iron accumulation in the substantia nigra may mediate age-related cognitive decline, and T2DM significantly accelerates this age-dependent iron deposition. 2. Stage 2. Type 2 diabetes (T2DM) raises the risk of memory and thinking problems, but the underlying brain changes remain unclear. Using quantitative susceptibility mapping technique to measure iron in deep brain structures in 115 T2DM patients and 176 healthy adults. T2DM group had higher iron in several brain regions but lower iron in caudate nucleus. Higher iron correlated with poorer memory and attention. Iron buildup in a brain region called the substantia nigra linked aging to cognitive decline, and diabetes amplified this effect. These findings indicate that abnormal iron regulation in the brain contributes to cognitive impairment in T2DM.
Carotid atherosclerosis is an established risk factor for cognitive impairment. FDG-PET detects subtle inflammatory changes in the arterial wall that may precede plaque formation and rupture. We investigated whether carotid inflammation is associated with cognitive function and its relative importance as a predictor of concurrent cognitive function compared with other factors. : In this cross-sectional study, we recruited individuals ≥40 years with undetectable viral load at moderate-to-high cardiovascular risk. Participants underwent FDG-PET, stress and cognitive assessments. We used pairwise partial correlations to identify significant associations between arterial inflammation and cognition. We applied a machine learning analysis workflow to evaluate the ability of carotid inflammation alone, and in combination with other factors, to predict cognition. Among 47 people, carotid inflammation was independently correlated with global cognition [r = -0.405, 95% confidence interval (CI) -0.618 to -0.100, P = 0.007]. In the machine learning analysis, the probability of carotid inflammation predicting cognitive function within one standard deviation of the true value was 68% (95% CI 52-80). The predictive accuracy improved marginally when individual cardiometabolic factors were added to the model (73%, 95% CI 57-84). When all potential variables were considered, predictive accuracy improved substantially (85%, 95% CI 71-93), with carotid inflammation remaining as the most important cardiometabolic predictor of cognitive function. Carotid inflammation on FDG-PET outperformed most other factors in predicting concurrent cognitive function and provided unique predictive information beyond traditional cardiometabolic risk factors. Future longitudinal studies should examine whether carotid inflammation predicts incident cognitive impairment, which would support its use as a clinical risk marker in people with HIV.
Mental process is a cornerstone of success in the rapid sports industry, where players must navigate high-pressure, dynamic environments. Cognitive flexibility is essential for adaptability and effective problem-solving, yet its relationship with negative psychological traits remains underexplored. This study investigates the mediating role of cognitive flexibility in the relationship between negative problem orientation and social problem-solving competence among esports players. The study sample consisted of 966 esports players from Türkiye, categorized as semi-professionals, professionals, and hardcore players. Data were collected using the Negative Problem Orientation Questionnaire, the Social Problem-Solving Skills Inventory, and the Cognitive Flexibility Scale. Statistical analysis was conducted using the SPSS PROCESS macro (Model 4), employing bootstrapping methods to evaluate the significance of direct and indirect effects within the mediation model. Mediation analysis revealed that cognitive flexibility significantly mediates the relationship between negative problem orientation and social problem-solving competence (indirect effect = 0.97, 95% CI [0.4805 1.485]). Direct effects were also significant: negative problem orientation predicted social problem-solving, while cognitive flexibility showed a strong positive impact on problem-solving competence. Cognitive flexibility serves as a vital psychological mechanism that may reduce the adverse influence of negative problem orientation and enhance social problem-solving competence in esports players. These findings suggest that interventions designed to strengthen cognitive flexibility such as scenario-based decision-making drills, mindfulness-based attention training, and stress-regulation exercises may contribute to better adaptability, psychological resilience, and problem-solving performance in competitive esports contexts.
Alzheimer's disease is associated with progressive cognitive, functional and social decline. Non-pharmacological interventions that combine cognitive and motor stimulation are increasingly used in long-term care, but less is known about the feasibility and preliminary effects of delivering such programmes in outdoor rather than indoor settings. This exploratory randomized single-blind pilot study compared outdoor and indoor cognitive-motor therapy in institutionalized older women with Alzheimer's disease, focusing on global cognitive performance, selected functional outcomes, attendance and practical implementation. Fifty women aged 66.1-70.2 years with late-onset Alzheimer's disease were randomized to a seven-month outdoor cognitive-motor programme (n = 25) or an indoor cognitive-motor programme (n = 25). Sessions were delivered five times weekly for 45 min. Outcome assessors and data analysts were blinded to group allocation; therapists and participants could not be blinded because of the intervention setting. Global cognition was assessed with the Mini-Mental State Examination (MMSE). Functional outcomes were assessed using modified FIM-based indicators for daily tasks, mobility and social adaptability. Attendance and adverse events were recorded as feasibility outcomes. All randomized participants completed the study. Mean attendance was 91% in the outdoor group and 89% in the indoor group, and no intervention-related adverse events were recorded. Both groups improved on the MMSE, with a median increase of approximately two points. The outdoor group showed statistically significant within-group improvements in all three FIM-based indicators (daily tasks, mobility and social adaptability), whereas the indoor group did not show statistically significant functional change. However, these broader gains were observed in the context of baseline functional imbalance, including lower outdoor-group mobility and social-adaptability scores, and the small female-only sample and partial non-equivalence of intervention content limit between-group causal interpretation. A seven-month cognitive-motor programme was feasible in participating long-term care facilities. The findings suggest that outdoor delivery may be associated with broader functional gains than indoor delivery, but the results should be interpreted as preliminary and in light of the baseline functional imbalance. A fully powered, prospectively registered trial with more equivalent intervention arms, repeated measurement points, standardized functional outcomes and detailed monitoring of comorbidities and medication changes is warranted.
Isoflurane-induced neuroinflammation triggers cognitive impairment in aged mice, but its underlying mechanism remains unclear. This study investigated the molecular mechanism by which isoflurane promotes glycolytic reprogramming to cause cognitive dysfunction in aged mice and identified potential therapeutic targets. 18-month-old mice were placed in an anaesthetic induction chamber containing 2% isoflurane (ISO) for 2 h to induce anaesthesia; this procedure was repeated daily for 5 days to establish a model of age-related cognitive impairment in mice. Behavioural studies in mice were conducted using the Y-Maze, contextual fear conditioning test (CFCT), Novel Object Recognition (NOR) test, and water maze test. Immunofluorescence analysis was employed to detect changes in the expression of microglia-related proteins PGK1, Hip, iNOS, Arg1, and P65. RT-PCR was employed to detect changes in mRNA expression levels of GLUT2, PKM2, HK2, and LDHA, which are associated with cellular metabolic reprogramming. ELISA was used to measure alterations in TNF-β, IL-4, IL-10, IL-6, IL-1β, and TNF-α cytokines. ISO enhanced glycolytic flux via PGK1, thereby driving microglia polarization toward the pro-inflammatory M1 phenotype and triggering neuroinflammation, ultimately leading to cognitive impairment in mice. Supplementing the glycolytic intermediate FBP reversed the anti-inflammatory effects induced by PGK1 knockdown, confirmed that PGK1 exerted its effects through the "PGK1-glycolysis axis." Mechanistically, PGK1 knockdown effectively suppressed M1 polarization of microglia while promoting their transition to the anti-inflammatory M2 phenotype. This significantly mitigated ISO-induced neuroinflammation and neuronal injury, ultimately improving cognitive function in mice. These findings reveal that PGK1 serves as a key molecular link between ISO anaesthesia and neuroinflammatory cognitive impairment. Targeting and inhibiting PGK1 exerts neuroprotective effects by reprogramming microglial glucose metabolism and phenotype, providing novel theoretical insights and potential therapeutic strategies for preventing ISO-induced neurological complications.
Rapid and effective enhancement of memory function through the integration of neuromodulation and cognitive training has been a longstanding objective in cognitive science and translational medicine. Research indicates that efficient training strategies are associated with rapid improvements in working memory (WM) performance, with successful WM performance linked to neural communication between frontomedial theta oscillations and posterior gamma oscillations. However, direct evidence showing how these strategies regulate neural communication and integrate neuromodulation to boost WM performance remains limited. This study addresses this gap by analyzing electroencephalography (EEG) data from participants undergoing strategy-based WM training combined with neuromodulation. We observed that WM enhancements were accompanied by altered coupling of theta-gamma oscillations. Then, targeted HD-transcranial Direct Current Stimulation (HD-tDCS) was applied to the left dorsolateral prefrontal cortex (LPFC), a region exhibiting representational similarity with behavior induced by the cognitive strategy implementation. This intervention resulted in enhanced WM performance associated with slower frontomedial theta oscillations. This study illuminates that cognitive-neural pattern plasticity can be rapidly and selectively improved through neuromodulation by leveraging spatial frequency coupling within specific cortical circuits involved in strategic memory.
Cognitive frailty, the coexistence of physical frailty and cognitive impairment, is closely linked to diabetes. This bibliometric analysis retrieved 2005-2024 literature from the Web of Science Core Collection and used CiteSpace to analyse publications, authors, institutions and keywords. The total of 175 papers showed steadily rising output. King's College London stood out institutionally, while Pasquale Mone and Gaetano Santulli were the most productive authors, revealing connections among insulin resistance, chronic inflammation and cognitive frailty. Recent keyword bursts focused on cognitive impairment and frailty. Research has turned to integrated clinical syndromes, with shared pathological pathways of insulin resistance and systemic inflammation as major future hotspots.
The NLRP3 inflammasome is a key immune regulator involved in the pathophysiology of neuroinflammation and various neurodegenerative diseases. Recent studies have shown that both activation and inhibition of the NLRP3 inflammasome can influence disease progression and symptoms in models of cognitive impairment, including Alzheimer's disease (AD). Red ginseng (RG), a traditional medicinal plant, possesses anti-inflammatory properties and shows potential for modulating the NLRP3 inflammasome pathway. This review highlights the effects of RG on the NLRP3 inflammasome, with a particular focus on its therapeutic potential in AD and related cognitive impairments. The structure and activation mechanism of the NLRP3 inflammasome are first described, followed by a discussion of its role in neurodegenerative diseases and neuroinflammation. We then explore how RG and its major components regulate the priming and activation phase of the NLRP3 inflammasome, and discuss their therapeutic potential based on findings from the neuroinflammatory-related cognitive impairment model. Furthermore, we identify supporting evidence for the application of the RG-NLRP3 mechanism in other central nervous system disorders (CNS) disorders, such as cerebral ischemia and vascular dementia. Overall, RG emerges as a promising therapeutic candidate for mitigating neuroinflammation and enhancing cognitive function in neuroinflammatory-related cognitive disorders through NLRP3 inflammasome regulation. Future studies using various neurodegenerative disease (NDD) models and clinical trials are necessary to further validate the therapeutic potential of the RG-NLRP3 pathway.
Although the cerebellum plays a role in the pathophysiology of motor symptoms in Parkinson's disease (PD), its association with cognition remains unclear. We investigated whether the cognition-related cerebellar lobules are associated with baseline and longitudinal cognition in PD. In this retrospective cohort study, we enrolled 203 drug-naïve patients with PD who underwent dopamine transporter (DAT) scans, high-resolution brain magnetic resonance imaging, and detailed neuropsychological testing at baseline. We analyzed the association of cerebellar lobular volume and cortical thickness with baseline cognitive domain composite scores and future PD dementia (PDD) conversion using multivariable linear regression analysis and the Cox proportional hazards model, respectively. We further tested whether striatal DAT availability moderated the cerebellar-cognitive associations. The volumes of cognitive cerebellar lobules were not significantly associated with cognitive domain scores. However, the cortical thickness of Crus II was positively associated with the baseline visuospatial score (β = 0.208, p = 0.004). Greater Crus II cortical thickness was also associated with lower risk of PDD conversion (hazard ratio [HR], 0.197; 95% confidence interval [CI], 0.071-0.544; p = 0.002). A Crus II x striatal DAT interaction was significant for both the baseline visuospatial score (β = -0.255, p = 0.001) and PDD conversion (HR = 0.61, p = 0.016). The effect of Crus II cortical thickness on PDD conversion was not mediated by the baseline visuospatial score. The cortical thickness of Crus II may serve as a cognitive brain reserve and be useful for predicting the risk of dementia conversion in PD.
Effective treatments for Alzheimer's disease (AD) are limited. Due to shared pathological mechanisms between AD and diabetes, antidiabetic drugs like sodium-glucose cotransporter-2 inhibitors (SGLT2is) are potential therapeutic options. Although SGLT2is have shown cognitive benefits in diabetes models, their effects in AD models are not fully established. This study aimed to evaluate the therapeutic effects of sotagliflozin (Sota), an SGLT2i, in both in vivo and in vitro AD models. The network pharmacology analysis was used to predict the potential targets and pathways of Sota. And we selected 6-month-old APP/PS1 transgenic mice to investigate the effects of Sota. Cognitive function was assessed using the Morris water maze test. Immunohistochemistry and immunofluorescence were employed to quantify amyloid-beta (Aβ) plaque deposition in the hippocampal or cortex and analyze neuronal loss. Additionally, amyloid β oligomers induction and microglial cells were used to evaluate the effects of Sota on the release of pro-inflammatory mediators and to investigate the underlying mechanisms. In vivo, Sota treatment improved cognitive impairments, reduced pro-inflammatory cytokines, inhibited microglial activation, and promoted neuronal survival. In vitro, Sota mitigated Aß oligomer-induced toxicity in microglial cells by decreasing reactive oxygen species and pro-inflammatory cytokine release. Mechanistically, Sota treatment was associated with suppression of extracellular signal-regulated kinase (ERK) signaling. Our findings suggest that Sota improved cognitive impairment and attenuates neuroinflammation in AD. Sota may be a promising candidate for the treatment of AD.

Interventions supporting medical care and enhancing quality of life in neurodegenerative or age-related cognitive decline are strongly needed. Electroencephalographic (EEG) neurofeedback can enable users to modulate their brain activity through real-time feedback. However, evidence for its clinical effectiveness remains inconclusive, partly due to limited personalization and insufficient task relevance of existing protocols.We tested whether personalized EEG neurofeedback supervised by deep neural networks (DNNs) can enhance cognitive performance in older adults (Gen X).
Approach:
Fifty-seven healthy adults aged 41-64 (31 women), including a sham-feedback control group, completed a personalized neurofeedback protocol with DNNs fine-tuned to individual EEG patterns. The procedure included pre- and post-training assessments using a transitive reasoning task, three diagnostic sessions to adapt the DNN to each participant, and 10-11 neurofeedback sessions based on a gamified delayed-match-to-sample paradigm. 
Main Results:
The training group showed robust gains across all three variants of the reasoning task (each p < .01), whereas the sham group improved only on the easiest variant. Groups did not differ at pretest; however, at posttest the training group outperformed the sham group on all task conditions (each p < .03), showing also a larger neural effort (lower alpha band power) and increased beta and gamma band connectivity (higher phase lag index). 
Significance:
Personalized, task-oriented neurofeedback guided by individually fine-tuned DNNs can produce cognitive enhancement after relatively few sessions. The proposed Task-Pretrained, Subject-Finetuned Neurofeedback (TPSF-NF) framework is scalable to other cognitive domains in future research.
Post-stroke cognitive impairment (PSCI) is a major rehabilitation concern. Traditional Chinese medicine (TCM) shows promise, yet a comprehensive, evidence-based evaluation of existing systematic reviews is lacking. This study aimed to map and evaluate the evidence on TCM interventions for PSCI, identifying strengths and gaps to inform clinical and research guidance. We searched PubMed, the Cochrane Library, Embase (via Ovid), and Web of Science, as well as Chinese databases including CNKI, Wanfang Database, the Chinese Medicine Database, and VIP Database (from their inception to December 2024) for systematic reviews or meta-analyses of TCM for PSCI. Two reviewers assessed methodological quality using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The results were synthesized using the population-intervention-comparison-outcome (PICO) framework and visualized as bubble plots in R software. A total of 36 systematic reviews (all from China) were included, covering acupuncture, herbal medicine, moxibustion, auricular stimulation, and TCM exercises. AMSTAR 2 rated 33 as "critically low" and 3 as "low." TCM demonstrated multidimensional benefits: cognitive function (36/36 beneficial), activities of daily living (26/27 beneficial), neurological function (5/5 beneficial), and overall effect (33 beneficial, 1 probably beneficial). TCM interventions may offer multidimensional benefits for PSCI, but the evidence is severely limited by critically low methodological quality. These findings should be considered hypothesis-generating. High-quality, prospectively registered systematic reviews and rigorous primary studies are urgently needed. CRD420251178410 (PROSPERO).
This study investigated behavioral and electrophysiological indices of cognitive performance in elite youth football players across mid-adolescence, interpreted through the Neural Efficiency Hypothesis (NEH) as a conceptual lens. Participants completed four cognitive tasks, the Tower of Hanoi (ToH), N-back, Iowa Gambling Task (IGT), and Sustained Attention to Response Task (SART), while electroencephalography (EEG) was recorded to extract power spectral density (PSD) and event-related potentials (ERPs). Behavioral results revealed no significant differences between younger and older players, suggesting relative stability in executive, attentional, and decision-making abilities during this developmental window. PSD analyses showed consistent region-specific modulations across tasks, including reduced frontal power and lower parietal beta and gamma activity, with the SART eliciting relatively higher alpha, beta, and gamma power consistent with its sustained attention demands. ERP amplitudes were largely stable across groups, with task- and lobe-specific effects such as enhanced occipital P2 activity during the IGT and reduced occipital N2/P2 amplitudes during the SART, reflecting differentiated neural recruitment for evaluative and inhibitory control processes. Brain-behavior correlations were modest but task-relevant. Overall, cortical activation patterns were strongly task-dependent yet descriptively stable across mid-adolescence. These findings provide a comprehensive baseline characterization of neural and cognitive function in elite youth athletes, informing future large-scale investigations of neural efficiency and developmental trajectories in sport contexts.
Alzheimer's disease (AD) features tau accumulation and pathogenic lipid droplet (LD) buildup, driving neurodegeneration through oxidative stress and neuroinflammation. The chaperone heat shock protein family A member 8 (HSPA8) is upregulated in AD, which may have implications for impaired LD clearance via lipophagy. We investigated whether targeting HSPA8 with the small-molecule antagonist VER155008 alleviates tau pathology and cognitive deficits by activating lipophagy in P301S tauopathy models. P301S tau transgenic mice and HEK293T-P301S cells were utilized. Western blotting, immunohistochemistry, and immunofluorescence were performed to assess HSPA8 levels, lipophagy, tau proteins, and inflammatory markers. VER155008 or vehicle control was administered to P301S mice for four weeks, starting at seven months of age. Cognitive function was evaluated using the Morris water maze and novel object recognition tests. Synaptic density was assessed through Golgi staining and electron microscopy. HSPA8 was elevated in P301S mice, correlating with impaired lipophagy and suppressed AMP-activated protein kinase (AMPK) activity. VER155008 treatment restored cognitive function and synaptic density. Critically, it activated lipophagy and reduced hippocampal LDs and tau pathology. Moreover, HSPA8 overexpression suppressed lipophagy and increased both LD accumulation and tau pathology. Inhibition of HSPA8 by VER155008 activates AMPK-mediated lipophagy, concurrently reducing tau pathology, oxidative stress, and neuroinflammation in AD models. These beneficial effects were eliminated by treatment with the AMPK inhibitor Compound C. This identifies the HSPA8-lipophagy axis as a promising therapeutic target for tauopathies.
The cognitive state modeling (CSM) problem is typically formulated as a classification problem, limiting the application of the CSM for adaptive real world applications, where the desired outputs are cognitive states to be desired and the inferred ones have to be used for decision making. While conventional methods classify states of the brain, they have not yet been able to connect the class to the task level. To address this, this paper suggests a neurosymbolic model of cognition as a continual latent process rather than an incremental labelling process. It includes a Pseudo Task based Neural State Encoder (PNSE) to encode EEG windows into a structured hyperspherical embedding space, a Neural Transition Graph Network (NTGN) to learn the relationships between cognitive states and tasks, and a Temporal Pseudo-Task Boundary Model (TPBM) to capture the temporal evolution of cognitive states. The neurosymbolic decision layer is used to produce a single scheduling metric using a neural compatibility score, a probabilistic transition measure and a symbolic fuzzy membership, while a fuzzy inference engine is used to categorize candidate task classes with fuzzy membership grades. The framework was tested on a multi-session multi-task EEG cognitive dataset (COG-BCI) using a protocol that was subject independent. The Silhouette Score, Hit Rate, Normalized Discounted Cumulative Gain (NDCG) and Mean Reciprocal Rank (MRR) achieved experimental results of 73.7%, 71.43%, 91.58% and 76.67%, respectively, in the fuzzy membership space. Moreover, the proposed system had a precision of 81.1%, a recall of 83.4% and achieved an accuracy of 83.47% and an F1 score of 82.7%. The outcomes illustrate the possibility of getting cognitive modelling from EEG data to enable active recognition of cognitive states, and the inference and scheduling of uncertain tasks. The proposed framework provides a tractable, temporally unified and cognitively flexible foundation for future decision-support systems that would benefit from both the interpretability and adaptability of neural representation learning and symbolic reasoning and temporal modelling.
Electronic health record phenotyping of cognitive decline may vary with the ontology used to encode diagnoses and findings. We compared ICD-10 and SNOMED CT representations of cognitive decline in the All of Us dataset. Separate ontology-specific feature sets were constructed and analyzed with k-means clustering as an exploratory method; clusters were summarized by condition burden, unique conditions, span, age, gender, and top-condition prevalence. Principal component analysis was used for visualization, and logistic regression was used to examine whether ontology-shaped features were informative for dementia classification. ICD-10 clusters were dominated by broad symptom-oriented terms, whereas SNOMED CT showed more differentiated groupings, including a normal-cognition cluster and a higher-burden dementia-related cluster. These findings suggest that ontology choice can influence latent phenotype structure and may affect the interpretability and performance of downstream classification in observational health data.
Social cognition, with emotion recognition (ER) being a key component, is recognized as a core cognitive domain, yet research on ER post-stroke remains limited. This exploratory pilot study aimed to provide preliminary estimates of long-term ER impairment after stroke and to examine its association with lesion volume and location. We invited patients <65 years, admitted for endovascular treatment (EVT) and included in a prospective cohort; the Oslo Acute Reperfusion Stroke Study, to participate in a 4-year follow-up study, and a healthy control (HC) group. ER was assessed using the "Pictures of Facial Affect" (PFA) test, impairment defined as performance ≥1.5 SD below HC mean. Linear regression analysis examined relationship between baseline predictors and ER at follow-up. Voxel-based lesion-symptom mapping (VLSM) were used to identify brain regions associated with ER, complemented by disconnectome mapping. Of 109 participants included, 40 completed a 4-year follow-up including the PFA test (24 (60%) women, mean age 51 (SD ± 10) years). ER impairment was detected in 9 (23%) patients. Stroke lesion volume was significantly associated with PFA scores in both univariable and multivariable analysis, adjusted for sex, education, and time to recanalization. VLSM revealed associations between right-hemisphere cortical regions and lower PFA scores, notably the inferior parietal lobule and and adjacent perisylvian cortex. Emotion recognition impairment was identified in more than one in five stroke patients four years after EVT. These preliminary findings identify stroke lesion burden and location as candidate group-level prognostic markers that warrant confirmation in larger studies of this under-researched cognitive domain.
Deep brain stimulation (DBS) is an established therapy for advanced Parkinson's disease (PD). However, its impact on neuropsychological outcomes remains controversial and lacks systematic integration. This study aims to systematically evaluate the effects of DBS on cognitive and neuropsychiatric symptoms in PD patients through a meta-analysis of randomized controlled trials (RCTs). A systematic search was conducted in databases including PubMed, Embase, the Cochrane Library, and Web of Science for RCTs comparing DBS with best medical treatment (BMT). Cognitive outcome measures included Verbal Fluency test, the Stroop Color and Word Test, the Wisconsin Card Sorting Test (WCST), and the Mattis Dementia Rating Scale (MDRS). Neuropsychiatric outcome measures encompassed Part I of the Unified Parkinson's Disease Rating Scale (UPDRS-I), the Beck Depression Inventory-II (BDI-II), the Montgomery-Asberg Depression Rating Scale (MADRS), as well as the Brief Anxiety Scale (BAS) and Beck Anxiety Inventory (BAI). Risk of bias was assessed using the Cochrane RoB 2 tool, and effect sizes were pooled using RevMan 5.4 software. A total of 10 randomized controlled trials involving 1,274 patients were included. Meta-analysis results indicated that, compared to BMT, patients undergoing DBS showed a more significant decline in performance on Verbal Fluency test and the Stroop Color-Word Interference Test. No statistically significant differences were observed between the two groups regarding overall cognitive function, cognitive flexibility, depressive symptoms, anxiety symptoms, or overall neuropsychiatric symptoms. Sensitivity analysis suggested that the effect of DBS on anxiety symptoms may vary across studies, indicating a potential beneficial role of DBS in this domain. DBS treatment did not lead to widespread cognitive or neuropsychiatric decline in patients with PD based on group-level analyses. However, within the assessed cognitive domains, mild, specific negative effects were observed on higher-order executive functions. Clinical decision-making should incorporate individualized neuropsychological assessment and monitoring to balance the benefits of motor symptom improvement with potential cognitive risks. https://www.crd.york.ac.uk/PROSPERO/recorddashboard, this meta-analysis has been registered on the PROSPERO platform (Registration number: CRD420251273115).
This study examined whether peripheral biological pathways including inflammation, insulin resistance, and arterial stiffness, partially explain the link between cardiorespiratory fitness (CRF) and cognitive function in older adults. In a cross-sectional sample of cognitively unimpaired older adults (N = 648, 71% female, M age = 69.88 ± 3.75 years), participants completed a comprehensive cognitive battery assessing executive function (EF)/Attentional control, episodic memory, processing speed, working memory, and visuospatial abilities. CRF was measured using a maximal graded exercise test performed on a motorized treadmill. Peripheral biomarkers included low-grade systemic inflammation (Interleukin-6; IL-6), insulin resistance (Homeostatic Model Assessment for Insulin Resistance; HOMA-IR) and arterial stiffness (carotid-femoral pulse wave velocity; cfPWV). Parallel mediation models, adjusted for age, sex, APOE4 carriage, body fat percentage, study site and years of education, tested whether these biomarkers statistically mediated associations between CRF and cognitive performance. IL-6 emerged as a consistent significant mediator of the relationship between CRF and EF, episodic memory, visuospatial processing and working memory. HOMA-IR statistically mediated the association between CRF and both EF and processing speed. In contrast, cfPWV did not statistically mediate an association between CRF and performance in any cognitive domain. These findings suggest that low-grade systemic inflammation broadly mediates the relationship between CRF and cognitive function, while metabolic pathways show more domain-specific associations. Together, these results highlight the need for understanding the plural, yet distinct, biological mechanisms by which higher CRF relates to better cognitive performance, with the goal of identifying potential targets for interventions aimed at preserving cognitive health in older adulthood.