Search Results (1,699)

Background/Objectives: Minor neurocognitive disorder (minor NCD) represents a heterogeneous and potentially modifiable stage along the continuum from normal aging to dementia, offering a critical window for targeted health promotion interventions. Early identification of individuals at increased risk of progression is essential for implementing preventive strategies that may delay functional decline. This study developed a transparent machine learning (ML) framework to predict diagnostic change from minor to major NCD at 12 and 24 months using baseline demographic, clinical, and multidomain neuropsychological data. Methods: A retrospective cohort of 162 memory clinic patients was analyzed using a rigorously controlled pipeline incorporating nested stratified cross-validation, SMOTE-based imbalance correction, and sequential forward feature selection. Logistic regression, support vector machines (SVMs), and XGBoost were evaluated, with SHapley Additive exPlanations (SHAPs) applied to ensure interpretability. Results: SVM achieved the most balanced predictive performance at both 12 months (accuracy = 0.90) and 24 months (accuracy = 0.81). Short-term progression was primarily driven by subtle multidomain cognitive inefficiencies, while longer-term risk reflected continued cognitive vulnerability modulated by metabolic factors such as diabetes. Conclusions: These findings highlight the potential of explainable ML as a health promotion tool and suggest that explainable ML can uncover clinically meaningful cognitive risk signatures at the earliest stages of NCD. By identifying modifiable systemic contributors alongside cognitive risk profiles, this framework supports precision-oriented preventive strategies and proactive longitudinal monitoring in minor NCD. Full article

Fibromyalgia (FM) is a complex chronic syndrome marked by widespread musculoskeletal pain, neurocognitive dysfunction (“fibro-fog”), and autonomic disturbances. Clinical management remains challenging due to subjective symptom reporting and the lack of definitive diagnostics. Emerging evidence points to a multifactorial origin involving central sensitization, neuroendocrine imbalance, and systemic immune-inflammatory alterations. A wide array of candidate biomarkers has been reported in FM, encompassing neurotransmitters (serotonin, norepinephrine), excitatory and inhibitory amino acids, metabolic and glycolytic enzymes, stress-related proteins, autoantibodies, oxidative stress markers and pro-inflammatory cytokines. This molecular heterogeneity reflects the systemic and multidimensional nature of FM. However, most of these biomarkers have been primarily investigated in serum or plasma, where analytical validation and reference ranges are more established. In contrast, the exploration of salivary biomarkers—although highly attractive due to its non-invasive, stress-free, and repeatable collection—remains comparatively limited. Saliva contains a reduced concentration range of many systemic markers and is strongly influenced by circadian rhythms, stress, flow rate, and oral health conditions. While promising candidates such as α-amylase, cortisol, calgranulins, and selected metabolic enzymes have shown potential in saliva, many proposed FM-related biomarkers lack full analytical validation, standardized protocols, and clinically defined reference intervals in this matrix. In this context, non-invasive electrochemical biosensors represent a transformative technological approach. Advanced electrode architectures incorporating nucleic acid probes, redox reporters, and nanostructured materials offer high sensitivity in low-volume and low-concentration biofluids such as saliva. The integration of multiplexed biomarker panels into portable platforms could enable real-time, longitudinal monitoring of FM pathophysiology, supporting phenotype stratification, personalized therapeutic adjustment, and objective disease activity tracking. Full article

Background/Objectives: The preschool period is critical for neurodevelopment, yet evidence investigating fortified formula’s effect and potential microbiota–gut–brain axis mechanisms in this age group is limited. To evaluate fortified formula milk’s effect on neurodevelopment and explore potential microbiota–gut–brain axis mechanisms in preschool children. Methods: In this 9-month cluster-randomized, double-blind, controlled trial, 120 healthy children aged 3–6 years from four kindergarten classes were stratified by grade and randomly allocated (1:1) to receive either multi-nutrient fortified formula (intervention, n = 60) or standard control milk (n = 60). Neurocognitive function was assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Safety was evaluated through anthropometry and blood biochemistry. Gut microbiota (16S rRNA sequencing) and fecal metabolomes (untargeted LC-MS) were analyzed at baseline and 9 months. Results: The intention-to-treat (ITT) analysis showed no significant difference in Full Scale Intelligence Quotient (adjusted mean difference: 1.05 points; 95% CI: −1.42, 3.52; p = 0.400). However, the intervention group significantly improved the Processing Speed Index (adjusted mean difference: 5.91 points; 95% CI: 1.88, 9.93; p = 0.004), increased gut microbial alpha diversity (Shannon index) and Bifidobacterium abundance. Metabolomic analysis revealed elevated fecal 2-hydroxybutyric acid (2-HB), a marker of propanoate metabolism. Increases in both Bifidobacterium and 2-HB levels showed a positive association with PSI improvement (both p < 0.05). All children maintained normal growth and safety parameters. Conclusions: Fortified formula milk improved processing speed in preschoolers, a benefit associated with gut ecosystem modulation characterized by Bifidobacterium enrichment and upregulated microbial propanoate metabolism. These results offer preliminary evidence for the role of the microbiota–gut–brain axis in nutritional cognitive programming during early childhood. (Clinical Trial Registry: ChiCTR2400084211). Full article

Background: Scientific interest has grown in naturally derived compounds capable of supporting or enhancing cognitive performance. Tanacetum vulgare L. is an abundant source of secondary metabolites and has been associated with a broad range of biological activities; however, its potential influence on cognitive function remains largely unexplored. Methods: The present study explored the effects of T. vulgare essential oil (EO) on cognitive performance, hippocampal brain-derived neurotrophic factor (BDNF) expression, and histomorphological alterations in a rat model. Animals were administered T. vulgare EO at doses of 0.5 and 1.5 mL/kg for 28 days and were subjected to a series of behavioral tests after one week of pretreatment. Results: Both doses of EO facilitated the formation of short- and long-term memory traces in the inhibitory avoidance tasks, with a more pronounced effect observed at the lower dose, whereas improvement in passive learning was evident only at the higher dose. Spatial and recognition memory were enhanced at both doses. EO treatment significantly increased hippocampal BDNF expression without inducing pathological alterations. Conclusions: These findings suggest that T. vulgare EO may improve specific hippocampal-dependent cognitive functions, with upregulation of hippocampal BDNF representing a potential underlying mechanism. Full article

Purpose: We hypothesised that cognition following consumption of an isomaltulose beverage would be comparable to that of an isoenergetic sucrose-based beverage, but the latter would attenuate post-ingestive metabolic responses. Methods: Thirty adults (15 males, 15 females) aged 21–44 years completed three experimental sessions, following at least 3 h fasting. Plasma insulin and glucose were measured in arterialised capillary blood 30 min after beverage consumption. Cognitive functions were assessed 45 min after beverage consumption using a computerised test battery; the primary cognitive performance outcome was a composite neurocognitive index score. Subjective symptoms were measured using questionnaires. Data are presented as the mean [95% confidence interval]. Results: Circulating glucose was greater after ingesting sucrose compared to isomaltulose and placebo beverages (sucrose: 7.3 [6.9, 7.7] mmol·L⁻¹; isomaltulose: 6.3 [6.1, 6.6] mmol·L⁻¹; and placebo: 5.3 [5.2, 5.4] mmol·L⁻¹). Insulin rose to a greater degree with sucrose compared to isomaltulose (mean difference = 8.5 [2.4, 14.6] µU·mL⁻¹, p = 0.005). Non-inferiority was shown between isomaltulose and sucrose for the composite neurocognitive index score (isomaltulose mean score = 0.931 [−2.3, 4.2]; sucrose mean score = 0.414 [−2.6, 3.5]). However, performance with the sucrose and placebo beverages was similar, limiting broader interpretation. The sensation of postprandial tiredness for isomaltulose was non-inferior to sucrose (isomaltulose mean score = −3.8 [−15.8, 8.2]; sucrose mean score = 0.1 [−10.9, 11.1]). Conclusions: A commercial stimulant beverage with isomaltulose as the energy substrate elicits substantial reductions in glycaemic and insulinaemic responses compared with an isoenergetic sucrose-based beverage, without compromising cognitive performance. Full article

Microglia, the resident macrophages of the central nervous system (CNS), serve as the primary reservoir of HIV-1 in the brain and play a crucial role in the development of HIV-1-associated neurocognitive disorders (HAND). While long non-coding RNAs (lncRNAs) have emerged as essential regulators of HIV-1 replication in T cells and macrophages, their role in microglia remains poorly understood. Here, we performed RNA sequencing of polyadenylated transcripts from a human microglial cell line exposed to HIV-1 infection or TNF-α stimulation to investigate transcriptional responses and identify lncRNAs with potential regulatory functions. Gene set enrichment analysis revealed broad overlap between viral and inflammatory responses, reflecting convergence on common molecular pathways. Among differentially expressed lncRNAs, we focused on TALAM1, which was specifically induced by HIV-1, and LINC00702, which responded to both HIV-1 and TNF-α. Validation by RT-qPCR confirmed the upregulation of TALAM1 and LINC00702 at 24 h post-infection. Furthermore, knockdown of either lncRNA affected viral genomic RNA levels, while only LINC00702 knockdown affected p55 production. Given that subcellular localization informs lncRNA function, we assessed the distribution of TALAM1 and LINC00702. TALAM1 was predominantly cytoplasmic under basal conditions but shifted toward nuclear enrichment upon HIV-1 infection, whereas LINC00702 remained primarily nuclear regardless of infection status. Consistent with their genomic context, protein interaction predictions, and pathway enrichment analyses suggested that TALAM1 may influence RNA processing and splicing, whereas LINC00702 may contribute to translational regulation and is associated with proteins involved in immune responses. Together, these findings provide an initial characterization of lncRNA responses to HIV-1 infection in a human microglial cell line and identify TALAM1 and LINC00702 as candidates for future functional studies in the context of viral infection and neuroinflammation. Full article

Background: Brain metastases are a major driver of cancer-associated morbidity and mortality, occurring in 20–40% of all malignancies. Objective: Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or observation after resection of 1–4 brain metastases. Methods: PRISMA-compliant search of Embase and MEDLINE from inception to August 2024. Overall survival (OS), cognitive decline (CD), surgical bed control (SBC), and intracranial control (IC) were assessed by pooling hazard ratios (HR) or 12-month post-SRS odds ratios (OR) via meta-analysis of proportions with random-effects modeling. Results: Of 1319 unique, English-language abstracts, 37 underwent full-text review, and 7 were included, representing 812 patients in three paired comparisons: WBRT vs. observation (4 RCTs, n = 545), WBRT vs. SRS (2 RCTs, n = 253), and SRS vs. observation (1 RCT, n = 132). Pooled HR were not significant for OS (WBRT vs. observation, HR = 1.01, 95% CI = 0.87–1.18; WBRT vs. SRS, 0.77, 95% CI = 0.47–1.26) or CD (WBRT vs. observation, HR = 0.98, 95% CI = 0.81–1.17; WBRT vs. SRS, 1.31, 95% CI = 0.48–3.60). Pooled OR favored WBRT over both observation and SRS with respect to SBC (SBC: WBRT vs. observation, OR = 1.35, 95% CI = 1.05–1.74; WBRT vs. SRS, OR = 1.46,95% CI = 1.00–2.13) and IC (IC: WBRT vs. observation, OR = 1.22, 95% CI = 1.06–1.40; WBRT vs. SRS, OR = 1.22, 95% CI = 1.03–1.59). GRADE assessment demonstrated very low to moderate certainty for all reported outcomes. Conclusions: Even among RCTs, the best available evidence regarding adjuvant treatment for oligometastatic brain disease is heterogeneous, imprecise, and inconclusive. WBRT improves SBC and IC, but not OS. SRS may decrease CD risk, which requires validation in double-blind RCTs incorporating precise neurocognitive metrics. Full article

Introduction: Chronic non-cancer pain represents a major global health challenge because of its high prevalence, functional impact, and limited response to conventional therapies, highlighting the need for alternative approaches. In this context, subanesthetic-dose ketamine has emerged as a promising therapeutic option because of its ability to modulate central sensitization and enhance analgesia through NMDA receptor antagonism. However, current evidence regarding its long-term efficacy and safety remains limited and heterogeneous. Objective: To evaluate the efficacy and safety of subanesthetic ketamine for the management of chronic non-cancer pain in adults, based on randomized controlled trials published between 2005 and 2025. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Randomized controlled trials involving adults with chronic non-cancer pain were included, comparing ketamine with placebo or other active agents. The databases searched were PubMed, ScienceDirect, and the Cochrane Library. Risk of bias was assessed using the Cochrane RoB-2 tool, and the certainty of evidence was evaluated using GRADE. Results: Five trials met the inclusion criteria. All included studies evaluated intravenous ketamine at doses ranging from 0.3 to 0.5 mg/kg. Overall, ketamine demonstrated significant short-term pain relief (p < 0.05), particularly in neuropathic conditions; however, the magnitude of this effect decreased progressively after the infusion ended. Reported adverse effects were mild and transient, with no evidence of severe toxicity. Heterogeneity in dosing protocols, pain phenotypes, comparator strategies, and follow-up duration limited cross-study comparability. Conclusions: Current evidence supports the short-term efficacy and safety of subanesthetic-dose ketamine as an analgesic option for chronic non-cancer pain, especially in neuropathic syndromes. However, the transient nature of its effects and the heterogeneity among studies underscore the need for standardized protocols and longer follow-up periods. Despite its generally favorable short-term safety profile, subanesthetic ketamine should be used with caution under strict clinical supervision, as the potential for long-term neurocognitive, urological, and hepatic adverse effects remains insufficiently defined. Full article

Background: Physical exercise has been increasingly recognized as a potential strategy to enhance cognitive development during childhood and adolescence. Among cognitive functions, attention plays a critical role in academic performance, behavioral regulation, and information processing. However, evidence regarding the specific effects of physical exercise on attentional performance in youth remains heterogeneous. Objective: This systematic review aimed to examine the effects of physical exercise interventions on attentional performance in children and adolescents. Methods: A systematic literature search was conducted in PubMed, Web of Science, Scopus, and CINAHL databases. Randomized controlled trials evaluating the effects of physical exercise interventions on attentional outcomes in participants aged 8 to 17 years were included. Study selection followed PRISMA guidelines. Nine studies met the inclusion criteria and were analyzed qualitatively. Results: The included studies consistently reported improvements in attentional performance following physical exercise interventions. Positive effects were observed across several attentional domains, including concentration, selective attention, sustained attention, processing speed, and response accuracy. Both acute and chronic exercise programs demonstrated cognitive benefits, although longer interventions appeared to produce more stable improvements. Coordinative and cognitively demanding exercise modalities tended to generate greater attentional gains compared with traditional physical activity programs. Conclusions: Physical exercise appears to be an effective non-pharmacological intervention for enhancing attentional performance in children and adolescents. Structured and cognitively engaging exercise programs may provide additional benefits for attentional development. Further research is needed to determine optimal exercise characteristics and to clarify the neurophysiological mechanisms underlying exercise-related attentional improvements. Full article

Cognitive impairment persists in people with HIV (PWH) despite effective combination antiretroviral therapy, possibly as a result of persistent alterations in white matter microstructural abnormalities in the brain. Noninvasive tensor-valued diffusion MRI (dMRI) is sensitive to microstructural integrity; thus, it may contribute to the understanding of HIV-associated cognitive impairment. In this exploratory cross-sectional study, 31 healthy controls (HCs) and 24 PWH underwent 3T MRI and neurocognitive assessment. Tensor-valued dMRI metrics, including microscopic fractional anisotropy (µFA) and isotropic, anisotropic, and total mean kurtosis (MKi, MKa, MKt), and conventional DTI and DKI metrics (FA, MD, and MK) were evaluated across six functionally defined brain networks. Compared with HCs, PWH exhibited reduced FA, µFA, and MKa in the dorsal default mode and anterior salience networks, along with increased MKi in the salience network and decreased MKi in the executive control network, with moderate effect sizes. Compared with HCs, PWH performed significantly worse on measures of learning, memory, and language, but showed no differences in executive function, attention, or processing speed. Additionally, significant associations and interactions between dMRI metrics and HIV status were observed, particularly for MKi and attention, executive function, and processing speed across the default mode, salience, and executive control networks. These preliminary findings underscore tensor-valued dMRI as a sensitive biomarker of network-specific neurocognitive vulnerability in HIV. Full article

Physical exercise can influence cognitive performance and neurobiological processes, but evidence spans diverse modalities, intensities, and adult populations. Acute exercise represents a state of transient skeletal muscle activation that induces systemic signaling through metabolic, endocrine, and myokine-mediated pathways, which may contribute to neurocognitive modulation. To map the breadth of acute exercise–cognition research, characterize cognitive and biological outcomes, and identify consistent patterns and gaps. Studies of adults (≥18 years) involving a single exercise session or short microcycle (≤7 days) with pre–post assessment of cognition and/or neurobiological markers across any exercise modality (aerobic, resistance, high-intensity interval training/HIIT, combined, vibration, mind–body) were included. PubMed and CENTRAL were systematically searched, yielding 101 studies. Data were extracted using a structured framework capturing exercise modality, dose, cognitive domains, biomarkers, neuroimaging outcomes, population characteristics, and study design features. Most studies examined young adults (53%) or older adults (32%). Aerobic exercise predominated (62%), followed by resistance (18%) and combined modalities (12%). Moderate-to-vigorous aerobic exercise consistently improved executive function, processing speed, and working memory. Resistance exercise also enhanced executive function in several trials (31 studies). Neurobiological correlates included increases in Brain-Derived Neurotrophic Factor (BDNF), lactate, catecholamines, and prefrontal activation, though variability in sampling limited mechanistic conclusions. Acute exercise is consistently associated with improvements in executive function and processing speed across modalities. Standardized exercise protocols, biomarker timing, and cognitive assessments are needed to strengthen mechanistic synthesis. Full article

Background/Objectives: To study the hypothesis that cognitive functions and learning skills are impaired in child/adolescent childhood cancer survivors (CCS). Secondary outcomes included psychosocial parameters and quality of life. Methods: This case–control study was conducted over four years (2017–2021) at the largest pediatric Aghia Sophia Children’s Hospital, in Greece. Eligible participants were children and adolescents in Greece. For CCS, ≥1 year should have elapsed from completion of cancer treatment. Assessments of neurocognitive function, learning and psychosocial skills and health-related quality of life (HRQoL) were performed with validated instruments (WISC-III, LAMDA software, Achenbach CBCL/6-18 and YSR, KIDSCREEN-52, respectively). Results: In total, 219 participants (47.49% males, mean age ± SD 11.72 ± 2.32 years), 70 CCS and 149 controls (matched for age, sex, family income), were included. Cases were CCS of acute lymphoblastic leukemia (n = 25)/brain tumors (n = 19)/lymphoma (n = 17)/nephroblastoma (n = 5)/Ewing sarcoma (n = 3)/rhabdomyosarcoma (n = 1). CCS had worse scores in full-scale Intelligence Quotient (FSIQ) (p = 0.004), verbal IQ (VIQ) (p = 0.005) and all its subscales, performance IQ (PIQ) (p = 0.021), and almost all learning parameters than controls. Attention, working memory, writing/visual–motor coordination, processing accuracy/speed, language acquisition/expression, all psychosocial scales, and HRQoL domains of mood and emotions, were negatively affected in CCS. Female CCS demonstrated lower FSIQ (p = 0.019) and VIQ (p = 0.014) than control females, whereas male CCS retained their total IQ unaffected. Among CCS, those with non-central nervous system (CNS) tumors, higher parental educational level or higher family income had significantly higher IQ than those with CNS tumors, lower parental educational level or lower family income, respectively. Conclusions: CCS in Greece carry a significant burden of cognitive and psychological morbidity. Cognitive/educational and psychosocial support to CCS is imperative. Full article

COVID-19 is increasingly recognized as a multisystemic disease with significant neurocognitive consequences. However, its specific impact on spatial memory, a cognitive domain essential for daily navigation and functional independence, remains insufficiently explored. This narrative review provides a critical synthesis of current evidence regarding spatial and visuospatial memory alterations across acute and post-acute phases, and post COVID-19 condition (PCC). Clinical findings, conventional and emerging assessment tools ranging from static tasks to immersive virtual reality environments, as well as potential neurobiological mechanisms, were considered. Results suggested that spatial memory is frequently compromised after COVID-19 disease, with deficits being most pronounced at longer retention intervals and within navigational contexts. Neuroimaging and biomarker data further reveal selective vulnerability in the medial temporal lobe, characterized by hippocampal atrophy, hypoperfusion, and disrupted functional connectivity. Importantly, traditional neuropsychological tools may underestimate these impairments due to limited ecological validity. Therefore, implementing multimodal assessment frameworks that integrate navigational paradigms is essential to enhance diagnostic sensitivity and facilitate the development of targeted rehabilitation strategies for PCC patients. Full article

Prosocial behavior is a core element of social harmony, and implicit prosocial attitudes, which may outperform explicit assessments in predicting real-world behavior, underscore their unique utility in prosocial and moral research contexts. Moreover, red songs, a distinctive musical form emerging in specific revolutionary and developmental periods of China, align with this prosocial potential, as they are characterized by lyrics advocating patriotism, collective memory, and emotional resonance. However, the specific effect of red songs on implicit prosocial attitudes, as well as the potential moderating role of music training experience in this relationship, remains underexplored. This study aimed to explore whether red songs enhance implicit prosocial attitudes compared to neutral songs, whether music training modulates this effect, and the underlying neural correlates using the Single-Category Implicit Association Test (SC-IAT) and event-related potentials (ERPs). A mixed-factorial design was used with 60 college students (30 with ≥5 years of music training, 30 without). Participants completed the SC-IAT (measuring implicit prosocial D-scores) while EEG data were recorded, while listening to red (“China in the Lantern Light”) and neutral (“Lake Baikal”) songs. ERP components (N1, P2, N3, LPCs) were analyzed. Behaviorally, no significant main effects of song type or music training were observed, but a significant interaction emerged (F(1, 58) = 4.09, p = 0.04): the music training group showed higher D-scores under red songs (M = 0.35, SD = 0.32) than neutral songs (M = 0.15, SD = 0.51), while the non-music training group exhibited the opposite non-significant trend. Neurally, repeated measures ANOVAs revealed a significant main effect of electrode site for N1 (F(4, 212) = 48.63, p < 0.001, partial η² = 0.48), with the largest amplitudes at FCz. Red songs elicited larger N1 amplitudes than neutral songs at Fz and FCz, and incongruent trials elicited larger N1 amplitudes at Pz. For P2, a main effect of condition was found (F(1, 52) = 7.02, p = 0.01), with larger amplitudes in incongruent trials, and a significant three-way interaction of song type, condition, and electrode site (F(4, 208) = 4.46, p = 0.006), with larger P2 amplitudes for red songs under incongruent trials at Fz. For N3, main effects of song type (F(1, 53) = 14.48, p < 0.001) and stimulus type (F(2, 106) = 8.32, p = 0.001) were observed; congruent trials elicited larger N3 amplitudes than incongruent trials at Fz and FCz. For LPCs, main effects of song type (F(1, 53) = 4.89, p = 0.03) and electrode site (F(4, 212) = 3.05, p = 0.047) were found, with the largest amplitudes at Pz and the smallest at FCz. Red songs enhance implicit prosocial attitudes specifically among individuals with music training, and are accompanied by multi-stage neurocognitive differences. These findings highlight the conditional effects of red songs and inform prosocial education. Full article