Search Results (1,892)

Magnetic resonance imaging (MRI)-based prediction of multiple sclerosis (MS) progression depends on how imaging data are prepared, represented, modelled, and evaluated. This systematic review synthesized artificial intelligence (AI) methods across the MRI-to-prediction pipeline. PubMed, Scopus, Web of Science, and Google Scholar were searched for studies published from 2010 to March 2026. Eligible studies included patients with MS or clinically isolated syndrome, used brain MRI directly or as the source of predictors, evaluated future progression-related outcomes, and reported quantitative predictive performance. Thirty-seven studies were included and synthesized narratively because of methodological and outcome heterogeneity. Prediction targets included CIS-to-MS/CDMS conversion, future MRI disease activity, PIRA/PIRMA, disability worsening or confirmed progression, future EDSS or disability status, and RRMS-to-SPMS conversion. Lesion morphology and location, radiomics, tissue atrophy, longitudinal imaging changes, and multimodal variables provided useful prognostic information. Classical machine learning (ML) remained effective for structured biomarkers, while deep learning (DL) enabled direct image-based modelling; neither approach was uniformly superior. PROBAST + AI assessment rated model Development as High concern in 35 of 37 studies and Unclear in two, Evaluation as High risk of bias in all 37 studies, and Applicability as Low concern in 32, Unclear in two, and High in three. Overall, MRI-based AI shows promising prognostic potential, while stronger data separation, calibration, transparent reporting, and independent validation are needed to support reproducible clinical translation. Full article

Introduction: Iron is essential for cerebral energy metabolism, neurotransmitter synthesis, myelination, and neural development. Iron deficiency may therefore impair brain function even before overt anemia develops. This systematic and mechanistic review synthesized EEG findings associated with iron deficiency across the lifespan and evaluated electrophysiological changes following iron treatment. Materials and Methods: PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycINFO, and Google Scholar were searched from inception to July 2026. Human studies examining iron deficiency or iron-deficiency anemia using EEG, quantitative EEG, task-related oscillations, event-related potentials, or cortical-evoked potentials formed the core evidence base. Two additional studies of chronic kidney disease-related or mixed-etiology anemia were retained as contextual evidence to help distinguish iron-specific electrophysiological effects from abnormalities associated more generally with anemia severity and reduced oxygen-carrying capacity. Risk of bias was assessed using RoB 2 and ROBINS-I. Because of substantial heterogeneity, findings were synthesized narratively. Results: Thirty reports were retained for narrative synthesis, covering participants from the neonatal period to adulthood. Twenty-eight formed the core iron-specific evidence base, whereas two were analyzed separately as contextual anemia evidence. Iron deficiency was commonly associated with increased slow-wave activity, reduced alpha activity, delayed sensory and cognitive processing, prolonged P300 and N2 latencies, altered frontal alpha asymmetry, and impaired differentiation between relevant and irrelevant stimuli. Reductions in P300 amplitude were less consistent but were observed in severe anemia, demanding cognitive tasks, and after infantile iron-deficiency anemia. Iron supplementation improved several spectral and ERP outcomes, although recovery was variable and some abnormalities persisted after hematological correction. Interpretation was limited by heterogeneous diagnostic criteria, small samples, inconsistent EEG methods, residual confounding, variable risk of bias, and the partial non-independence of reports arising from overlapping longitudinal cohorts or parent trials. Findings from the contextual anemia studies were not interpreted as direct evidence of an effect of iron deficiency. Conclusions: Iron deficiency may disrupt the timing, synchronization, and maturation of neural activity through impaired energy metabolism, neurotransmission, myelination, and synaptic development. EEG may be useful for detecting functional brain alterations and monitoring treatment response, but no specific electrophysiological biomarker can currently be established. Full article

Inflammation is a complex biological response involved in the pathophysiology of several chronic diseases. Although conventional anti-inflammatory therapies are effective, their prolonged use can be associated with relevant adverse effects. Although non-steroidal anti-inflammatory drugs and glucocorticoids are widely used, these agents cause gastrointestinal, renal, cardiovascular, hepatic and metabolic adverse effects. Essential oils (EO) exhibit relevant anti-inflammatory potential. However, their pharmaceutical application is limited by volatility, hydrophobicity, physicochemical instability and potentially low bioavailability. This review evaluated EO-loaded lipid nanocarriers for anti-inflammatory applications, with emphasis on physicochemical quality attributes, stability, safety and efficacy. Literature searches were carried out through PubMed/MEDLINE, PubMed Central, ScienceDirect, SciELO, Virtual Health Library, and Google Scholar websites, based on works published between 2021 and 2026. The investigated systems included liposomes, solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions. Different formulations were found regarding EO nature, nanocarrier type, administration route and biological models used, predominantly involving preclinical assays. Nanoencapsulation was frequently associated with suitable physicochemical properties and release profiles, but direct comparisons with the corresponding free EO and control nanocarriers were not consistently performed. Safety findings were mainly based on cytotoxicity, local tolerability and short-term assays, with limited repeated-dose and long-term toxicological data. Several formulations showed anti-inflammatory activity in acute, subacute, or chronic experimental models. In selected works using the same experimental conditions, some formulations produced responses of similar magnitude to hydrocortisone, diclofenac, or other anti-inflammatory drugs, but these results cannot be directly correlated with therapeutic equivalence. The reported mechanisms involved modulation of the NF-κB, MAPK and Keap1/Nrf2/HO-1 signaling pathways. Overall, lipid-based nanocarriers represent platforms for investigating the stability, delivery and biological performance of EO. However, further standardization and controlled assays are required to determine their therapeutic and translational potential. Full article

Background: Ventilator-associated pneumonia (VAP) is a common and serious nosocomial infection in mechanically ventilated preterm infants and is increasingly caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative organisms. Tigecycline, a glycylcycline with broad activity against many such pathogens, is not approved below 18 years of age and carries a boxed warning for excess mortality that is most pronounced in hospital-acquired and ventilator-associated pneumonia. Its role, if any, in preterm infants with VAP is undefined. Objectives: To systematically identify and appraise all human evidence on the efficacy (clinical cure, microbiological eradication, survival) and safety (adverse events, mortality) of tigecycline used to treat VAP or nosocomial pneumonia during mechanical ventilation in preterm infants and neonates. Methods: A PRISMA 2020 structured search of PubMed/MEDLINE, Cochrane CENTRAL, Scopus, trial registries, regulatory documents, Google Scholar and reference lists was designed without language or date restrictions. Eligible reports described tigecycline treatment of pneumonia/VAP in neonates or young infants; pediatric case series and syntheses were retained as contextual evidence. Because only case reports and small non-comparative series were anticipated, a narrative synthesis was pre-specified; JBI tools and GRADE were planned for appraisal and certainty. Results: No randomized controlled trial, controlled observational study, or study dedicated to tigecycline for VAP in preterm infants was identified. Direct evidence meeting the full eligibility criteria (preterm neonate, VAP specifically, separately extractable outcomes) was limited to two case reports of extremely preterm neonates with VAP successfully weaned after tigecycline-based salvage combination therapy. Six further neonatal/young-infant reports initially considered were, on full-text re-review, reclassified as contextual (not index) evidence because they described non-VAP infections (sepsis, or CNS infections such as ventriculitis/meningitis), non-preterm ages, or mixed-infection series without separable VAP data. Reported outcomes were generally favorable in published cases but are subject to severe selection and publication bias; thrombocytopenia, hypofibrinogenemia and hepatic enzyme elevation were the principal adverse signals, against a class-level mortality signal concentrated in VAP. Quantitative pooling was not appropriate. The overall certainty of evidence was very low. Conclusions: There is no direct, credible efficacy or safety evidence supporting tigecycline for VAP in preterm infants. Available data neither establish benefit nor exclude harm. Based on this very-low-certainty evidence and on regulatory/class-level safety data rather than on demonstrated efficacy, tigecycline warrants consideration only as a last-resort, combination salvage option for culture-confirmed pan- or extensively drug-resistant pathogens when no safer alternative exists, with intensive monitoring and, ideally, within a registry or trial. Adequately designed neonatal pharmacokinetic and comparative safety studies are urgently needed. Registration: PROSPERO CRD420261450972 (registered 14 July 2026). Full article

Visual analytics combines computational analysis with interactive visual representations and may strengthen pharmacovigilance, but its use in drug safety research has not been systematically characterized. This scoping review mapped the extent, characteristics, and applications of visualization and visual analytics in pharmacovigilance and identified evidence gaps. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidance, we searched PubMed, IEEE Xplore, Web of Science, Scopus, and Google Scholar from inception through April 2026. Two reviewers independently selected studies and extracted data, which were synthesized qualitatively using predefined frameworks covering pharmacovigilance activities, analytical methods, visual representations, and interaction capabilities. Sixty-seven studies met the eligibility criteria: 41 system design studies and 26 non-system studies. Of the designed systems, 29 were classified as visual analytics systems and 12 as interactive visualization systems. Signal management was the most frequently supported activity; plots and charts were the predominant visual representations; and selecting, filtering, and drilling were the most common interactions. Only 16 systems reported formal evaluations. Visual analytics has been applied across diverse pharmacovigilance activities, particularly signal management, but the field remains limited by incomplete end-to-end workflow support, restricted analytical transparency, limited integration of complementary evidence sources, and infrequent formal evaluation of designed systems. Full article

Background/Objectives: Energy drinks are marketed to adolescents as products that enhance alertness, concentration, and physical or sports performance, yet their use may also represent a visible marker of sleep debt and a potential contributor to disrupted 24 h behavioral patterns. This narrative review examines evidence linking energy drink consumption with adolescent sleep disturbance and considers implications for obesity risk, cognition, and physical activity. Methods: Targeted literature searches were conducted in PubMed/MEDLINE, ScienceDirect, Google Scholar, and reference lists to identify reviews, consensus statements, policy documents, and adolescent-relevant observational or experimental studies. Evidence was synthesized narratively and classified as strong, moderate, limited, or hypothesis-generating according to study design, consistency, age specificity, and directness to the proposed pathway. Results: The strongest evidence supports associations between energy drink use and short or poor-quality sleep, and between sleep dimensions and adolescent adiposity. Experimental adolescent studies support links between sleep restriction, food choice, reward processing, cognition, and self-regulation. Evidence linking energy drink use directly to reduced physical activity is weaker and likely depends on timing, context, and user subgroup. Sugary and sugar-free products require separate interpretation: sugar-containing drinks may contribute directly to energy intake, whereas sugar-free products may still disrupt sleep through caffeine and may not remove behavioral risk. Conclusions: Energy drink use should be considered not only as caffeine or sugar exposure, but also as a screening cue for sleep debt, fatigue, sedentary behavior, and physical activity readiness. Reducing energy drink use alone is unlikely to resolve adolescent sleep debt; multifactorial interventions that combine caffeine-timing guidance, sleep hygiene, screen management, physical activity support, and policy-level access strategies are needed. Full article

Psychoactive nitrogen-containing compounds represent a structurally diverse group of natural and synthetic molecules whose interactions with metal ions influence their physicochemical properties, biological activity, and analytical behavior. Although numerous studies have reported the synthesis of metal complexes, solution interactions, and metal-assisted analytical methods, the available knowledge remains scattered across compound classes and has not been comprehensively evaluated. This review summarizes advances in the coordination chemistry of psychoactive nitrogen-containing compounds from ScienceDirect, Google Scholar, and the Cambridge Structural Database (CSD), emphasizing donor atoms, coordination modes, structural diversity, crystallographic characterization, spectroscopic and computational investigations, and the biological properties of the resulting metal complexes. The current literature demonstrates that metal complexation can alter molecular geometry, electronic structure, redox behavior, biomolecular recognition, and pharmacological activity, while also offering opportunities to develop compounds with enhanced antimicrobial, anticancer, antioxidant, and DNA-binding properties. By integrating coordination behavior, structural, and biological aspects within a single framework, this review highlights the central role of metal interactions in psychoactive compounds and identifies emerging opportunities to develop advanced analytical methodologies and functional metal-based systems. Full article

Background/Objectives: The period between 12 and 16 years of age coincides with peak pubertal change, declining habitual physical activity, and the consolidation of lifelong behavioral patterns, making it a critical window for understanding how fitness develops and how stable (or unstable) it is over time. This review aims to synthesize longitudinal evidence addressing how HRPF changes and tracks in adolescents aged approximately 12 to 16 years, the sex- and maturation-related modifiers of these patterns, the methodological approaches used to assess them, and the secular and behavioral context within which they occur. Methods: A structured narrative review was conducted searching four electronic databases—Google Scholar, PubMed, Web of Science, and Scopus—using terms combining concepts of adolescence, health-related physical fitness, and longitudinal study design published up to April 2026. Reference lists of retrieved systematic reviews and meta-analyses were snowball-searched. Eligible studies employed longitudinal or repeated-measures designs in samples overlapping the 12–16-year age range; no formal risk-of-bias appraisal or quantitative pooling was undertaken, consistent with the narrative-review design. Findings were synthesized narratively by HRPF component and thematic domain. Results: Cardiorespiratory fitness rises through early adolescence before plateauing or declining from approximately age 15 in one longitudinal cohort, more markedly in boys; muscular power and strength diverge increasingly by sex, a pattern consistent with androgen-mediated gains in lean mass in boys, although this mechanism was not directly tested here; flexibility remains the most stable component; and body composition acts as both an outcome and a determinant of other fitness test performance. Within-adolescence tracking is moderate-to-high for most components in the single available 3-year cohort of adolescent girls that reported component-specific tracking coefficients (e.g., lower-limb power β = 0.98, aerobic endurance β = 0.75, trunk muscular endurance β = 0.51), and substantially stronger than tracking from childhood into adolescence. Secular trends indicate population-level fitness has declined in many countries over recent decades, with adolescents showing greater decline than children. Conclusions: Early-to-mid adolescence appears to be a critical and time-limited opportunity to consider for fitness-promoting intervention: fitness rank is still somewhat malleable, but shows progressively stronger tracking with age—a pattern of rank stability that should not itself be read as evidence about responsiveness to intervention. Methodological heterogeneity in test batteries, follow-up duration, and tracking statistics limits direct comparability across studies. Future research should incorporate maturity-status indicators, multi-wave designs, and harmonized assessment protocols. Full article

Sleep bruxism is the rhythmic or nonrhythmic masticatory muscle activity that occurs during sleep. It is conventionally diagnosed by a rule-based algorithm. Candidate muscle bursts are flagged against a fixed electromyographic (EMG) amplitude threshold, classified by duration into phasic, tonic, or mixed episodes, and counted into an hourly rate compared against a second threshold. These thresholds generalize poorly across individuals and nights. This has motivated a growing body of artificial intelligence (AI) research aimed at replacing one or more stages of this classical algorithm with a learned decision function. This paper synthesizes that literature as a technical pipeline across 28 reviewed AI-based sleep bruxism studies, identified through Web of Science and Google Scholar searches for “sleep bruxism” combined with artificial intelligence terms, conducted in 2026, and screened for a learned, trained classification approach reported in English. These accuracy figures should be read alongside several complicating factors. Ten studies draw on the same subset of two patients from a public polysomnography database. Several studies framed as sleep bruxism detection were validated only on awake, simulated grinding. In addition, the ground-truth labels these classifiers are trained against remain contested within the field’s own consensus literature. The paper’s contribution is therefore twofold. It assembles the pipeline synthesis itself, spanning ground truth, recording modality, preprocessing, feature extraction, and architecture, as a technical reference not previously brought together in this form. It also uses that synthesis to set a concrete research agenda, including validation benchmarks across nights and across subjects, a shift from binary toward continuous severity targets, and an extension of detection into real-time treatment devices and clinical prognosis. Full article

Cancer nanomedicine has generated extensive preclinical evidence of improved drug delivery, pharmacokinetics, and tolerability, yet its clinical impact has often remained modest. This narrative review examines the interconnected biological, pharmacokinetic, manufacturing, regulatory, and clinical factors underlying this translational paradox. A structured literature search was conducted primarily in PubMed and Google Scholar, focusing on studies published between 2022 and 2026 while retaining seminal earlier reports. Major biological barriers include protein corona formation, mononuclear phagocyte system clearance, heterogeneous enhanced permeability and retention, complex tumor microenvironments, and intratumoral heterogeneity. These factors limit circulation, tumor accumulation, tissue penetration, drug release, and interpatient reproducibility. Translation is further constrained by off-target accumulation, uncertain long-term toxicity, non-standardized experimental methods, batch-to-batch variability, scale-up challenges, and fragmented regulatory pathways. Clinical experience shows that successful products are dominated by relatively established platforms and reformulations of known anticancer agents, whereas many actively targeted or structurally complex systems have failed to demonstrate sufficient efficacy or safety. Future progress will require mechanism-driven design, human-relevant preclinical models, harmonized characterization, quality-by-design manufacturing, early regulatory integration, biomarker-guided patient selection, and adaptive clinical trials. Aligning nanoparticle engineering with biological and clinical realities is essential for achieving meaningful patient benefit. Full article

Diabetes mellitus is a major global health challenge, and medicinal plants represent an important source of bioactive compounds with therapeutic potential. Ibervillea sonorae (S. Watson) Greene is traditionally used in Mexican medicine for diabetes management and has attracted increasing scientific interest because of its reported antihyperglycemic activity. This systematic review critically evaluated the available preclinical evidence regarding the antihyperglycemic effects of I. sonorae, its proposed molecular mechanisms, phytochemical context, and methodological limitations. Following the PRISMA 2020 guidelines, PubMed, Scopus, and Google Scholar were searched for studies published between January 2010 and February 2026. Eight studies met the inclusion criteria, including animal, cellular, and enzyme-based models. The available evidence indicates that I. sonorae preparations may improve glycemic control through complementary mechanisms involving enhanced glucose uptake and insulin-related responses, including participation of the PI3K/AKT/GLUT4 signaling network, together with inhibition of α-glucosidase and α-amylase activity. AMPK-related mechanisms remain biologically plausible but have not been directly established across the included studies. Phytochemical evidence identifies cucurbitacin-derived constituents, including kinoins, as potentially relevant bioactive compounds; however, most mechanistic findings were obtained using crude extracts or other plant preparations, and their specific contribution cannot yet be attributed to individual constituents. Overall, this review integrates the fragmented preclinical evidence and identifies the principal mechanistic, phytochemical, and methodological gaps that must be addressed before clinical translation. I. sonorae represents a promising candidate for antihyperglycemic research, although phytochemical standardization, rigorous mechanistic studies, comprehensive safety evaluation, and well-designed clinical investigations are required to establish its therapeutic efficacy and safety. Full article

Laurus nobilis L. (Lauraceae), widely recognized as bay laurel, has long held prominence in traditional medicine across diverse cultures and has attracted growing attention within contemporary pharmacological research. This review endeavors to synthesize and critically evaluate evidence from in vitro, in vivo, and clinical studies to elucidate the therapeutic potential of this species, an aromatic evergreen shrub native to the Mediterranean region. Its leaves and essential oil have long been utilized in culinary and traditional medicine, and recent scientific studies have revealed a wide range of pharmacological properties. A comprehensive literature search was conducted using the keyword “Laurus nobilis L.” across Scopus, PubMed, and Google Scholar databases. The search included English-language resources published up to 31 January 2025, focusing on in vitro, in vivo, and human studies. Exclusion criteria encompassed letters, conference proceedings, and articles related to agriculture, genetics, nursing, environmental and veterinary sciences, multidisciplinary studies, and non-medical or pharmaceutical themes. The findings indicate that L. nobilis exhibits diverse pharmacological activities, including wound-healing, dental plaque-reduction, hepatoprotective and gastroprotective effects, antidiabetic activity, antioxidant and anti-inflammatory properties, antimicrobial and antiparasitic effects, neuroprotective potential, antigenotoxic and anti-hypersensitivity actions, and renal protection. This review manuscript seeks to further illuminate the pharmacological potential of Laurus nobilis while articulating the biophysical underpinnings and mechanistic coherence through which its bioactive constituents manifest their therapeutic effects. In conclusion, L. nobilis demonstrates significant promise as a natural, effective, and safe therapeutic candidate for various health conditions. Nonetheless, further clinical research is warranted to substantiate its efficacy and safety, thereby enabling its integration into evidence-based medical practice. Full article

Heavy metal contamination of agricultural soils and urban green spaces has become a major environmental concern, threatening ecosystem functioning, food safety, and sustainable land management. Silicon-based growing media have emerged as an environmentally friendly approach for reducing metal mobility while enhancing plant establishment in contaminated environments. Despite growing research interest, a comprehensive evaluation of the mechanisms, effectiveness, and practical applications of silicon-amended growing media across diverse plant systems remains lacking. This systematic review addresses this gap by synthesizing current evidence following the PRISMA 2020 framework. A systematic search of Web of Science, Scopus, PubMed, ResearchGate and Google Scholar identified 247 publications published between 2010 and 2025, of which 32 peer-reviewed studies met the predefined inclusion criteria for qualitative analysis. The reviewed literature demonstrates that silicon incorporation into growing media improves substrate functionality by modifying physicochemical properties, immobilizing heavy metals, regulating metal transport within plants, strengthening antioxidant and osmo-protective defense systems, preserving photosynthetic activity, and improving nutrient acquisition and water-use efficiency. Furthermore, silicon influences molecular signaling pathways and promotes beneficial rhizosphere interactions that collectively enhance plant resilience under metal stress. Among the evaluated materials, silicon nanoparticles consistently exhibited greater remediation efficiency than conventional silicon sources because of their higher surface reactivity and improved bioavailability. Overall, silicon-based substrate engineering represents a multifunctional and sustainable strategy for mitigating heavy metal contamination while improving the performance of agricultural crops and urban vegetation. Future research should focus on validating these findings under long-term field conditions, optimizing silicon formulations for different substrate types and contamination scenarios, evaluating environmental safety, and integrating silicon-based technologies into climate-resilient agricultural practices and urban green infrastructure. Full article

Background: Drug-resistant epilepsy (DRE) affects approximately one-third of individuals with epilepsy, where seizures remain uncontrolled despite appropriate trials of at least two antiseizure medications (ASMs). Neuroinflammation, specifically chronic microglial activation, plays an important role in epileptogenesis, seizure perpetuation, and pharmacoresistance. Traditionally, antiseizure medications (ASMs) target neuronal excitability through modulation of ion channels and neurotransmitter systems; however, several ASMs, including sodium valproate and lamotrigine, have demonstrated anti-inflammatory and microglia-modulating properties beyond their conventional antiseizure mechanisms. Rational polytherapy involving combinations of ASMs with complementary mechanisms and anti-neuroinflammatory effects may provide enhanced seizure control while minimizing adverse effects. Among available combinations, sodium valproate and lamotrigine have consistently been regarded as one of the few combinations demonstrating potential pharmacodynamic synergism. Although several clinical studies have evaluated this combination in pediatric DRE, the overall evidence has not been quantitatively synthesized. Objectives: To systematically evaluate the efficacy and safety of rational polytherapy with sodium valproate plus lamotrigine in children with drug-resistant epilepsy. Methods: Electronic databases, including PubMed, Medline, Scopus, Embase, Web of Science, Google Scholar, PubMed Central, ScienceDirect, Cochrane Library, and clinicaltrials.gov, were systematically searched. Studies involving pediatric patients aged 18 years or less with DRE receiving polytherapy regimens containing sodium valproate plus lamotrigine were included. Primary outcomes were total treatment effect defined as ≥50% seizure reduction and seizure freedom. Secondary outcomes included changes in seizure frequency, adverse events, treatment discontinuation, and serious adverse events. Risk of bias was assessed using the Cochrane Risk of Bias tool and Newcastle–Ottawa Scale. Meta-analyses were performed using random-effects models. Results: A total of 7 studies met the eligibility criteria. The pooled proportion of patients achieving an overall treatment response was 65.3% (95% CI 51.8–78.8%), with high heterogeneity (I² = 63.4%, p = 0.027). Rational polytherapy with sodium valproate plus lamotrigine combination provided preliminary comparative evidence of higher responder rates in a single comparative trial, requiring confirmation in larger randomized trials. Overall, sodium valproate plus lamotrigine was well tolerated, and most reported adverse events were mild to moderate in severity. The pooled adverse event rate was 18.1% (95% CI 8.3–28.0%), with high heterogeneity (I² = 64.3%, p = 0.024). Conclusions: Rational polytherapy with sodium valproate plus lamotrigine that have both complementary antiseizure and immunomodulatory mechanisms appears to represent an effective and generally well-tolerated therapeutic strategy for pediatric drug-resistant epilepsy. However, the basis of this conclusion is derived mainly from observational studies, requiring confirmation in larger randomized trials. This systematic review provides quantitative evidence supporting its clinical use while highlighting the need for larger prospective comparative studies to strengthen the evidence base. Full article

Background: Age-related cognitive decline is a major public health challenge, and modifiable lifestyle factors such as physical exercise and sleep have emerged as promising targets for preserving cognitive health. Our review aimed to synthesize evidence on the relationships between physical exercise, sleep, and cognitive performance in adults aged ≥60 years, with particular emphasis on the potential mediating or moderating role of sleep. Methods: Electronic searches were conducted in PubMed/MEDLINE, EMBASE, the Cochrane Library, Scopus, Web of Science, and Google Scholar to identify studies published between 2015 and 2025. Eligible studies evaluated structured exercise interventions or habitual physical activity and reported at least one sleep outcome alongside at least one cognitive outcome. Results: Twelve studies met the inclusion criteria, comprising randomized controlled trials, non-randomized intervention studies, and observational studies. Moderate-intensity aerobic exercise, multicomponent training, and mind–body interventions were the most frequently investigated exercise modalities. Across studies, exercise was generally associated with improved sleep quality and maintenance or enhancement of cognitive performance. Several studies identified sleep quality or sleep efficiency as potential mediators or moderators of exercise-related cognitive benefits; however, heterogeneity in study designs, interventions, sleep assessments, and cognitive outcomes precluded conclusions regarding causality. Conclusions: Current evidence suggests that sleep may represent an important behavioral pathway through which exercise contributes to cognitive health in older adults. Further well-designed randomized controlled trials incorporating objective sleep measures and mechanistic biomarkers are warranted to clarify these relationships. Full article