Search Results (6,103)

Background: Features intersecting neurological and psychiatric disorders impose differential diagnostic challenges, especially in younger, healthy patients. Cognitive biases, such as diagnostic overshadowing, can lead to errors for patients with neurologic deficits in the presence of psychiatric comorbidities. Methods: This case report describes a 22-year-old female patient admitted for acute inpatient rehabilitation with an initial primary diagnosis of Functional Neurologic Disorder (FND), who subsequently underwent additional neurologic work-up following clinical and functional inconsistencies. Results: Physical exam findings, lack of response to therapeutic modalities, and electromyography/nerve conduction study findings led to a full neurological work-up consistent with Acute Motor and Sensory Axonal Neuropathy (AMSAN), treated with intravenous immunoglobulin. Conclusions: Systemic peripheral neuropathies must be addressed during differential diagnosis in suspected FND, a potential gap in current practice. This report emphasizes the essential role of physiatry and the value of an unbiased, patient-centered approach, integrating clinical knowledge and compassion to ensure accurate diagnosis and appropriate treatment. Full article

Background: Language impairment is a core feature of Major Neurocognitive Disorder (MND), yet the domain-specific relationship between language functioning and everyday functional status remains insufficiently characterized. Methods: We conducted a retrospective observational study in 125 older adults diagnosed with MND according to DSM-5 criteria with mild-to-moderate cognitive impairment measured with Mini-Mental State Examination (MMSE). Language performance was assessed using semantic, phonemic verbal fluency and confrontation naming. Functional status was evaluated using basic (BADL) and instrumental activities of daily living (IADL). Ordinal logistic regression models examined associations between language domains and functional outcomes, adjusting for global cognitive status (MMSE), demographic variables, multimorbidity, and depressive symptoms. Model fit was evaluated using the Akaike Information Criterion. Results: Semantic fluency emerged as the best-performing predictor of BADL across all hierarchical models, remaining statistically significant after full adjustment for MMSE and clinical covariates (β ≈ 0.60, p < 0.05). Phonemic fluency showed the most robust association with IADL, with a stable effect across models, reaching a trend toward statistical significance in the fully adjusted analyses (β ≈ 0.22–0.27, p = 0.069). Naming ability did not influence functional outcomes. All observed associations persisted after controlling for MMSE, demographic variables, multimorbidity, and depressive symptoms. Conclusions: Language abilities showed differential associations across language domains with functional status in this sample of patients with MND. Semantic fluency was associated with basic self-care, while phonemic fluency showed a trend toward association with instrumental daily activities. These relationships remained observable after adjustment for global cognitive impairment, suggesting verbal fluency as a potentially sensitive marker of functional vulnerability. Full article

Posttraumatic stress disorder (PTSD) has been associated with a range of cognitive alterations; however, the relationship between PTSD and intelligence remains unclear. The aim of this systematic review was to examine potential differences in intelligence associated with exposure to traumatic events and/or a diagnosis of PTSD in adults aged 18 years and older. A systematic search was conducted across three major academic databases—PsycINFO, MEDLINE, and Web of Science—to identify empirical studies assessing intelligence or closely related cognitive constructs in individuals with PTSD or a history of trauma exposure. After applying predefined inclusion criteria, 12 studies were included in the review. Intelligence was assessed using various psychometric instruments, encompassing both global intelligence measures and specific domains such as verbal intelligence and vocabulary. Overall, the findings consistently indicated a negative association between intelligence and PTSD, with lower intelligence scores more frequently observed among individuals with PTSD or significant traumatic exposure. Due to the correlational design of the studies included, causal relationships cannot be established. Consequently, it remains unclear whether intelligence is affected by PTSD or whether higher intelligence may serve as a protective factor against the development or severity of the disorder. From an intelligence research perspective, these findings highlight cognitive ability as a key factor associated with vulnerability and resilience in trauma-related psychopathology. Full article

Background: Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked lysosomal storage disorder caused by pathogenic variants in the iduronate-2-sulfatase gene, leading to progressive multisystem involvement. Although international management guidelines exist, challenges in their implementation across different healthcare systems remain insufficiently addressed. This study aimed to establish a national expert consensus in Türkiye on the treatment and management of MPS II, aligning local practice with international standards. Methods: A modified Delphi methodology was conducted using two rounds of online surveys supported by three steering committee meetings. The process involved 10 experienced clinicians and a scientific committee of six professors. Based on international guidelines and country-specific clinical challenges, 72 consensus statements and 84 exploratory questions were developed. Statements achieving ≥ 80% agreement were accepted as consensus. Results: Consensus supported initiating enzyme replacement therapy (ERT) in both severe and attenuated MPS II, guided by functional and cognitive status. Severe cognitive impairment was not considered an exclusion criterion for ERT, given its somatic benefits. Experts agreed on continuing ERT into adulthood with individualized discontinuation decisions. Routine evaluations every 6–12 months, including respiratory, cardiac, and neurocognitive assessments, were recommended. Additional consensus areas included individualized premedication strategies, structured transition to adult care, selective home infusion, annual patient-reported outcome assessments, and the establishment of a national MPS II registry. Hematopoietic stem cell transplantation was not endorsed. Conclusions: This Delphi study demonstrates strong expert consensus on MPS II management in Türkiye, providing a practical framework to guide clinical practice, support alignment with international recommendations, and inform future policy and research priorities. Full article

Background/Objectives: Freezing of gait (FOG) and sleep disturbances are common in people with Parkinson’s disease (PwPD). A bidirectional association between them has been suggested, but quantitative evaluations are scarce. This study aimed to compare sleep disturbances in mild-to-moderate PwPD with (PD+FOG) and without FOG (PD−FOG), and to assess the association between FOG severity and sleep parameters. Methods: Data from 54 PwPD with disease stage <4 and no severe cognitive decline were included (27 PD+FOG and 27 propensity score-matched for age, sex, and disease duration PD−FOG). Demographics and clinical variables were collected. Clinical assessment included the new freezing of gait questionnaire (NFOG-Q), Parkinson’s Disease Sleep Scale (PDSS-2), Epworth Sleepiness Scale (ESS) and Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Mann–Whitney U, Fisher’s exact and Spearman’s tests were used for group comparisons and correlations, respectively. Results: Significant differences were observed between PD+FOG and PD−FOG groups in MDS-UPDRS part II (p = 0.011) and part IV (p = 0.011), with higher scores in PD+FOG participants. No significant differences were found in PDSS-2 or ESS between the two groups. A significant moderate positive correlation was found between NFOG-Q score and PDSS-2 (ρ = 0.416; p = 0.044) in PD+FOG participants. Conclusions: FOG severity was positively associated with sleep disturbances within the PD+FOG group. However, no significant difference in sleep quality or excessive daytime sleepiness was found between PD+FOG and PD−FOG after propensity score matching. PD+FOG participants experienced more severe motor complications and greater impairment in daily activities compared to PD−FOG. Full article

Background: Chronic stress is a major risk factor for cognitive decline and blood–brain barrier (BBB) disruption, yet the underlying molecular mechanisms remain elusive. This study aimed to investigate the specific role of the metabolic intermediate homocysteine (Hcy) in chronic stress-induced BBB dysfunction and cognitive impairment. Methods: We utilized a male Sprague-Dawley rat model of chronic unpredictable mild stress (CUMS) and administered vitamin B complex to lower Hcy levels in vivo. Regional Hcy accumulation, BBB permeability, and cognitive behaviors were assessed. In vitro, primary rat brain microvascular endothelial cells (BMECs) were exposed to Hcy to evaluate barrier-forming function, transcriptomic alterations, DNA methylation patterns, Cav1.2 expression, and reactive oxygen species (ROS) production. Results: CUMS selectively induced BBB hyperpermeability and significant Hcy accumulation predominantly within the rat hippocampus, which correlated intimately with cognitive deficits. Lowering Hcy levels via vitamin B supplementation successfully restored hippocampal BBB integrity and alleviated cognitive impairment. In addition, elevated Hcy severely impaired the barrier function of BMECs. Mechanistically, Hcy reduced global DNA methylation in BMECs and specifically induced targeted DNA hypomethylation at the intro region of Cacna1c. This epigenetic shift caused the transcriptional derepression and overexpression of the Cav1.2 calcium channel. Upregulated Cav1.2 subsequently triggered a robust ROS burst, leading to tight junction degradation. Conclusions: Our findings unveil a novel metabolic–epigenetic axis where Hcy-driven Cacna1c hypomethylation directly disrupts BMECs function to dismantle the hippocampal BBB. Lowering Hcy or targeting this Hcy-Cav1.2 pathway establishes a promising therapeutic strategy for mitigating stress-related neurovascular damage and cognitive disorders. Full article

Dopamine (DA) is essential for motor control, motivation, and cognition, and its dysregulation is associated with neurological and psychiatric disorders such as Parkinson’s disease, schizophrenia, and addiction. Accurate and selective DA quantification in complex biological matrices is important, but remains challenging because of coexisting interferents and the low physiological concentration of DA. Here, we report a disposable electrochemical DA sensor based on screen-printed carbon electrodes (SPCEs) modified with metal–organic framework-derived gold nanocomposites (MOFD-AuNCs). The optimal material, synthesized with a 60 min NaBH₄ reduction step (MOFD-AuNC-60), exhibited superior electron-transfer kinetics compared with materials prepared at other reduction times. A single coating of MOFD-AuNC-60 on SPCEs enabled DA oxidation at a low potential (~0.05 V) with high selectivity in the presence of ascorbic acid and uric acid. In undiluted porcine serum, the sensor exhibited a dynamic range of 2.5–500 nM with a calculated detection limit of 0.5 nM. In undiluted human serum, it exhibited a dynamic range of 5–100 nM with a calculated detection limit of 4.4 nM. The MOFD-AuNC-60/SPCEs further demonstrated excellent reproducibility (relative standard deviation, 3%) and stability (7.5% current loss over 7 days). These results demonstrate that the proposed sensor provides a disposable, robust, and reliable sensing platform for direct DA detection in undiluted serum, showing promise for practical applications. Full article

Stock market investors and traders operate in high-pressure environments marked by volatility, uncertainty, financial risk, and intense performance demands. These conditions lead to substantial psychological distress, increasing vulnerability to psychiatric disorders and suicidal behavior. Key psychological risk factors in this population include acute financial loss, chronic stress, impulsivity, perfectionism, and identity fusion with professional performance. Evidence from behavioral psychology and clinical psychiatry indicates elevated rates of mood disorders, anxiety, and burnout in trading environments. Resilience—including emotional regulation, effective stress-coping mechanisms, strong social support, and cognitive flexibility—emerges as a critical protective factor that mitigates suicide risk and promotes adaptive functioning. Strengthening psychological resilience and implementing evidence-based mental-health strategies may help reduce suicide risk and support overall well-being. The medico-legal dimensions of this issue encompass duty of care within high-stress financial workplaces, clinical obligations related to suicide risk assessment and documentation, confidentiality and safety considerations, and questions of foreseeability of suicide in cases involving severe or catastrophic financial loss. Despite growing awareness of mental health challenges in financial professions, the intersection of suicide risk, resilience, and medico-legal responsibilities in this population remains underexplored. Further research is needed to refine assessment frameworks and develop targeted suicide prevention interventions for this at-risk group. Full article

Neuropsychiatric disorders are characterized by complex etiologies, widespread involvement of brain regions, and pronounced clinical heterogeneity, with core pathological mechanisms closely associated with abnormal activity in deep brain structures and their functional networks. Although current pharmacological therapies and conventional neuromodulation techniques have shown therapeutic benefits in certain conditions, they are generally limited by insufficient stimulation depth or the risks associated with invasive procedures. Temporal interference (TI) electrical stimulation has recently emerged as a non-invasive deep neuromodulation technique that generates low-frequency difference-envelope fields through high-frequency carrier signals, thereby enabling relatively precise modulation of deep brain regions while maintaining favorable safety and tolerability. This technique provides a novel technical pathway for precision intervention in neuropsychiatric disorders. In this review, we summarize the principles and technical characteristics of TI stimulation and highlight its recent applications in mood and stress-related disorders, cognitive impairment and neurodegenerative diseases, movement disorders, addiction, and disorders associated with dysregulated neural excitability. We integrate its potential mechanisms across multiple levels, including neural oscillations, deep–cortical network synchronization, reward and motivational circuits, synaptic plasticity and structural remodeling, excitatory-inhibitory balance, and gene and epigenetic regulation. Current evidence suggests that TI stimulation can modulate electrophysiological activity and may engage molecular and network-level processes relevant to functional improvement, although durable clinical benefits remain to be established. Although clinical translation remains challenged by parameter optimization, interindividual variability, and long-term safety evaluation, advances in computational modeling, multimodal neuroimaging, and closed-loop stimulation strategies are expected to facilitate its development. Overall, TI stimulation represents a promising non-invasive deep neuromodulation approach for mechanistic investigation and precision treatment of neuropsychiatric disorders. Full article

Astrocytes are now recognized as active and essential participants in neural circuit function, extending far beyond their traditional roles as passive support cells. Emerging evidence highlights their critical involvement in synaptic modulation, information processing, and complex behaviors, making them key targets for understanding cognitive dysfunction in psychiatric disorders. This narrative review synthesizes current findings from rodent models to elucidate the relationship between astrocytic networks and multidomain cognitive performance. We first outline the morphological and physiological features of astrocytes, followed by a comprehensive overview of the modern experimental toolkit, including observational markers and advanced interventional strategies. Next, we evaluate commonly used behavioral assays that capture distinct cognitive domains, ranging from basic spatial and recognition memory to higher-order executive functions, cognitive flexibility, and social cognition. By integrating recent experimental evidence, we detail the specific mechanistic pathways, such as intracellular calcium signaling, gliotransmission, and neuroinflammatory reactivity, through which astrocytes directly govern these cognitive processes. Finally, we highlight critical knowledge gaps stemming from methodological limitations, arguing for the integration of more ethologically relevant, high-throughput behavioral tasks alongside highly specific targeting tools to better capture the functional heterogeneity of astrocytes in cognitive health and disease. Full article

Background/Objectives: Diet is a primary and modifiable determinant of gut microbiota composition, diversity, and metabolic activity, thereby shaping microbial-derived metabolites, immune and inflammatory signalling, neuroendocrine regulation, and neural communication with the central nervous system. Western dietary patterns, characterised by high intake of ultra-processed foods, saturated fats, and low dietary fibre, are consistently associated with gut dysbiosis, impaired intestinal barrier function, chronic low-grade inflammation, and increased risk of depression, anxiety, cognitive impairment, and neurodegenerative disorders. Methods: This narrative review synthesises evidence from human observational studies, randomised controlled trials, animal models, and mechanistic investigations examining interactions among diet, gut microbiota, and mental health or neurobiological outcomes. Literature searches were conducted in PubMed, Scopus, and Web of Science for articles published up to December 2025. Results: The study highlights the therapeutic potential and limitations of dietary interventions, prebiotics, probiotics, and psychobiotics, and critically evaluates them. Also facilitates an improved understanding of diet–microbiome–brain interactions, which may help the development of personalised, nutrition-based strategies integrated into mental health prevention and clinical care. Conclusions: These findings support diet-based, microbiome-informed strategies as scalable adjuncts in mental health prevention and care. Full article

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition affecting over 10–20% of individuals older than 70 years, characterized by the expansion of hematopoietic stem cell clones carrying somatic mutations in leukemia-associated driver genes in the absence of overt hematologic disease. Initially recognized as a precursor to hematologic malignancies, CHIP has since been implicated in diverse non-malignant disorders, notably increasing the risk of cardiovascular events by 40%. Recent epidemiological and experimental evidence suggests a potential disease-modifying influence of CHIP in neurodegenerative diseases, particularly Alzheimer’s disease (AD), although findings remain heterogeneous and sometimes contradictory. This review synthesizes recent evidence linking CHIP to AD risk, neuropathology, and disease progression. In this study, we summarize population-based cohort studies reporting a 36 to 54% reduction in the odds of clinical AD among CHIP carriers, alongside emerging data indicating that DNMT3A and TET2 mutations may exert divergent effects on neurodegeneration. Mechanistic insights from experimental models are examined, highlighting the ability of mutated myeloid cells to infiltrate the central nervous system and modulate neuroinflammation and amyloid clearance. We discuss conflicting findings and analyze how CHIP-driven vascular disease and stroke confound neuroprotective signals. We propose that CHIP may differentially influence AD and vascular contributions to cognitive impairment and dementia, shaping mixed dementia phenotypes. Methodological challenges, including survivor bias, competing risks, variable mutation detection thresholds, and incomplete Apolipoprotein E stratification, are discussed. Ultimately, our review clarifies that CHIP is not a simple protective factor, but a complex systemic modulator that reshapes the neurodegenerative and vascular drivers of cognitive decline, necessitating cross-disciplinary neuro-hematology collaboration to establish its role as a novel risk stratificator for improving diagnostic precision and personalizing clinical outcomes in Alzheimer’s disease. Full article

Alzheimer’s disease (AD) is increasingly recognized as a multisystem neurodegenerative disorder in which sensory dysfunction accompanies cognitive decline. As an accessible extension of the central nervous system, the retina provides a valuable window for investigating early neurodegenerative processes; however, the cellular mechanisms underlying AD-associated retinal pathology remain incompletely understood. Here, using the APP/PS1 mouse model, we systematically examined structural, functional, and glial alterations in the retina across disease stages. Despite robust age-dependent amyloid plaque accumulation in visual-related brain regions, no plaque-like β-amyloid (Aβ) deposits were detected in the retina even at advanced ages. Nevertheless, young APP/PS1 mice exhibited early thinning of inner retinal layers, impaired retinal electrophysiological responses, and reduced excitatory synaptic inputs to retinal ganglion cells (RGCs), preceding overt neuronal loss. These neuronal changes were accompanied by pronounced Müller glial activation, characterized by upregulation of gliosis markers and extensive morphological remodeling. Functional analyses further revealed dynamic alterations in glial homeostasis, including early elevation followed by age-dependent decline of glutamine synthetase activity, together with increased expression and disrupted perivascular polarity of aquaporin-4. Consistently, transcriptomic profiling of young AD retinas identified coordinated dysregulation of genes involved in amino acid metabolism, transport, and oxidative stress responses. Together, our findings identify Müller glial remodeling as an early feature of AD-associated retinal pathology that coincides with synaptic vulnerability of RGCs and occurs independently of local Aβ plaque deposition, highlighting retinal glia as potential early indicators and modulators of neurodegeneration. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive decline and neuropathological hallmarks such as amyloid-β plaques and neurofibrillary tangles. In recent years, chronic neuroinflammation has emerged as a central mechanism linking genetic, metabolic, and immune dysfunctions in AD. Activated microglia and astrocytes release pro-inflammatory cytokines and reactive oxygen species that exacerbate synaptic and neuronal injury, while impaired clearance mechanisms and blood–brain barrier disruption further sustain inflammation. A growing body of research highlights the role of immunometabolism—the bidirectional interaction between immune activation and cellular metabolism—in shaping glial phenotypes and disease progression. Dysregulation of glucose, lipid, and amino acid metabolism, together with alterations in key metabolites such as lactate, NAD⁺, and reactive oxygen species, promotes a maladaptive inflammatory state. Genetic factors including APOE4 and TREM2 variants affect microglial lipid handling pathways, while systemic metabolic disorders and gut microbiota alterations amplify neuroinflammatory cascades. Natural bioactive compounds, particularly polyphenols, have gained attention for their ability to modulate immunometabolic pathways. By activating AMPK and SIRT1 and inhibiting mTOR and NLRP3 inflammasome signaling, polyphenols may tune mitochondrial function, redox homeostasis, and autophagy, promoting adaptation to chronic metabolic stress. Therefore, metabolic-immune interactions represent pleiotropic therapeutic avenues for AD. Understanding how immunometabolites and nutrient-sensing pathways regulate compartmentalized inflammation in the CNS may pave the way for novel interventions that combine metabolic precision with neuroprotective efficacy. Full article

Introduction: Previous research has shown that L-carnosine (β-alanyl-L-histidine) can reduce cognitive decline and improve mental health outcomes, but an updated systematic review of the effects of carnosine alone or in combination with other supplemental nutrients or bioactive compounds on these interconnected outcomes is lacking. Methods: We searched multiple databases from 1 January 2006 to 30 June 2025 for clinical trials evaluating the effects of all forms of carnosine (e.g., L-carnosine, zinc–L-carnosine) alone or in combination with other supplements on cognition, brain structure and function, mood, depression, or quality of life (QOL) outcomes. The Cochrane Risk of Bias (ROB) 2.0 tool was used to assess the ROB in randomized controlled trials (RCTs). When data were sufficient, random-effects meta-analyses were conducted. Strength of evidence (SoE) across studies was rated using the GRADE approach. Results: A total of 13 distinct studies (12 RCTs; 1 single-arm trial) involving healthy adults and patients with psychiatric or neurocognitive disorders were included. Studies were also heterogeneous in carnosine supplement dosage and duration. Overall 58% of included RCTs were rated ‘some concerns’ for ROB. Ten RCTs evaluated cognitive function, seven RCTs and one single-arm trial assessed mood and depression, four RCTs measured QOL, and three RCTs examined brain structure and function. Results from five RCTs found no significant differences in the majority of the cognitive function measures between L-carnosine supplement and placebo, but random-effects meta-analysis of three RCTs from a single research team found that anserine/L-carnosine supplementation significantly improved WMS-LM2 scores (pooled net change = 1.70; 95% CI 0.19, 3.2; I² = 58.3%) but not WMS–Local Memory Immediate Recall (LM1) scores (pooled net change = 0.76; 95% CI −0.18, 1.71; I² = 8.5%). Additionally, meta-analysis results showed that L-carnosine combined with anserine or antioxidant supplementation significantly improved the MMSE score compared to placebo (pooled net change = 0.62; 95% CI 0.23, 1.01), with small statistical heterogeneity (I² = 21.3%). Most of the studies did not show significant effects in a wide range of mood and depression outcome measures or health-related QOL (data cannot be meta-analyzed). Conclusions: A low strength of evidence suggests that L-carnosine supplement combined with anserine or antioxidants can slow cognitive function decline among healthy elderly or patients with probable Alzheimer’s Disease or mild neurocognitive disorder. More high-quality RCTs are needed to verify these findings and to improve the certainty level of this body of evidence. Full article