Search Results (314)

Epidemiological and clinical research on neurodegenerative diseases has shown that metabolic dysregulations increase the risk of developing Alzheimer’s Disease (AD). Many metabolic changes can be grouped into metabolic syndrome (MetS), which is defined as the presence of three or more risk factors, including insulin resistance, hyperglycemia, hypertension, central obesity, and dyslipidemia. These changes cause systemic effects that are crucial in triggering neuroinflammation and neurodegeneration, key factors in AD development. All these factors impair energy metabolism in peripheral tissues and the brain by decreasing glucose utilization, leading to alterations in O-GlcNAcylation, glycosylation, mitochondrial function, oxidative stress, chronic inflammation, synaptic dysfunction, autophagy impairment, and blood–brain barrier (BBB) dysfunction. However, these factors are modified and largely influenced by lifestyle choices. A newer perspective emphasizes that regular exercise is vital for maintaining brain metabolism as we age. Current evidence suggests that engaging in physical activity for individuals with metabolic syndrome reduces their risk of Alzheimer’s disease, enhances prognosis, and improves cognitive abilities. This review explores how metabolic syndrome relates to Alzheimer’s and highlights possible strategies for prevention and treatment. Full article

Background/Objectives: Major depressive disorder (MDD) remains a leading cause of disability worldwide and exhibits substantial biological heterogeneity that is not adequately captured by current symptom-based diagnostic systems. While the classical monoamine hypothesis has historically guided antidepressant development, it does not fully account for variability in treatment response, delayed therapeutic onset, or the persistence of cognitive and anhedonic symptoms. Converging evidence from molecular, neuroimaging, and translational studies increasingly implicates glutamatergic dysregulation and impaired neuroplasticity as key mechanisms in depressive pathology. This narrative review aims to integrate monoaminergic and glutamatergic perspectives within a dimensional framework that may help explain clinical heterogeneity and inform mechanism-based treatment strategies. Methods: A narrative synthesis of the literature was conducted using major biomedical databases including PubMed, Scopus, and Web of Science. Preclinical studies, neuroimaging investigations, biomarker research, randomized clinical trials, and meta-analyses examining monoaminergic dysfunction, glutamatergic signaling, neuroplasticity pathways, and rapid-acting antidepressants were reviewed and thematically integrated. Results: Evidence indicates that depressive syndromes may reflect varying contributions of monoaminergic dysregulation and glutamatergic–neuroplastic impairment. Monoaminergic disturbances interact with inflammatory and neuroendocrine processes, including cytokine-driven activation of the kynurenine pathway. In parallel, alterations in glutamatergic signaling, glial function, and BDNF–TrkB–mTOR pathways contribute to synaptic atrophy and network dysfunction. Rapid-acting antidepressants such as ketamine, esketamine, and dextromethorphan–bupropion provide clinical proof-of-concept that direct engagement of synaptic plasticity mechanisms can accelerate symptom improvement, particularly in treatment-resistant depression. Conclusions: Integrating monoaminergic and glutamatergic mechanisms within a “monoamine–glutamate continuum” offers a conceptual framework for understanding depressive heterogeneity and treatment response. Multimodal approaches combining clinical phenotyping with inflammatory, neuroimaging, and molecular markers may ultimately support mechanism-informed precision psychiatry strategies in major depressive disorder. Full article

Background: Migraine in older adults represents an increasingly relevant yet underrecognized clinical challenge in aging societies, where multimorbidity, frailty, and polypharmacy complicate both diagnosis and management. Although traditionally considered a disorder of younger individuals, migraine frequently persists or presents after the age of 60 with atypical features, contributing to diagnostic uncertainty. Methods: This narrative review, conducted in accordance with the SANRA principles, aims to provide a comprehensive overview of the epidemiology, clinical presentation, pathophysiology, and management of migraine in older adults, with particular emphasis on age-related complexities, therapeutic challenges, and unmet clinical needs. Results: Migraine in this population often presents with atypical or misleading features, such as aura without headache, vestibular symptoms, or overlap with cerebrovascular conditions, leading to delayed or incorrect diagnoses. The burden of disease is substantial, affecting physical function, mobility, cognition, emotional well-being, and social participation, and is further amplified by comorbid conditions including cardiovascular and metabolic disorders, mood disturbances, and chronic pain syndromes. Aging-related neurobiological changes, such as impaired pain modulation, endothelial dysfunction, and neuroinflammation, may influence disease expression and treatment response. Therapeutic management is challenged by contraindications, increased susceptibility to adverse drug effects, and the complexity of polypharmacy, highlighting the importance of individualized and non-pharmacological approaches. Conclusions: Migraine in older adults is a significant but often overlooked contributor to disability and reduced quality of life. Improved recognition of its unique clinical features and age-specific vulnerabilities is essential to optimize patient-centered care. Future research should prioritize the inclusion of older populations and the development of tailored, safe, and effective management strategies. Full article

Background/Objectives: Constipation is a common gastrointestinal problem in older adults and is associated with reduced quality of life, functional decline, frailty, and an increased risk of delirium and cognitive impairment. Its pathogenesis is multifactorial, involving age-related changes in gastrointestinal motility, neural regulation, comorbidities, and polypharmacy. However, this condition has traditionally been regarded as a localized gastrointestinal disorder, which may not fully reflect its systemic clinical significance in older populations. While prior narrative reviews have described multifactorial contributors to constipation, none have formally applied a geriatric syndrome framework to integrate these dimensions. This review proposes a three-criterion operational definition—multifactorial pathogenesis, association with functional decline and frailty, and contribution to adverse systemic outcomes—to characterize constipation in older adults as a “systemic geriatric syndrome,” and evaluates available evidence against each criterion. Methods: A narrative literature search was conducted using PubMed to identify relevant studies published between 1 January 2023, and 31 December 2025. MeSH terms included “Constipation” [Major Topic] and “Aged” [MeSH Terms]. Eligible articles included English-language original studies, systematic reviews, and clinical or epidemiological studies involving individuals aged ≥65 years. Results: Diagnosis in older adults is often complicated by secondary causes, including medications and neurological disorders, as well as atypical symptom presentations in individuals with cognitive impairment. Key pathophysiological mechanisms include reductions in interstitial cells of Cajal, impaired smooth muscle contractility, dysfunction of the enteric and autonomic nervous systems, and gut microbiota dysbiosis, which may promote chronic low-grade inflammation. Major contributing factors include physical inactivity, sarcopenia, dehydration, inappropriate defecation posture, and polypharmacy, particularly opioids and anticholinergic agents. Importantly, these factors interact through the brain–gut–microbiota axis, contributing not only to gastrointestinal dysfunction but also to systemic outcomes such as frailty, cognitive decline, and increased healthcare burden, thereby supporting a multidimensional disease framework. Conclusions: The available evidence collectively supports the plausibility of framing constipation in older adults as a systemic geriatric syndrome, though formal validation of this classification requires further longitudinal and mechanistic research. Comprehensive and individualized management strategies, extending beyond simple laxative use, are essential to reduce complications and preserve functional health in aging populations. Further studies are required to validate this framework. Full article

Canine Cognitive Dysfunction Syndrome (CCDS) is a progressive neurodegenerative disease affecting older dogs that shares many pathological mechanisms with human Alzheimer’s disease (AD). Although it is common in geriatric dogs, CCDS is often underdiagnosed in veterinary medicine. Both CCDS and AD involve a gradual decline in cognitive functions such as memory, learning and executive abilities. From a pathological perspective, dogs with CCDS show brain changes similar to those seen in AD, including cerebral atrophy, loss of neurons and accumulation of amyloid-beta plaques. CCDS is diagnosed by exclusion, meaning that other medical or neurological conditions that could cause similar behavioural signs must first be ruled out. Clinical evaluation mainly relies on structured questionnaires completed by owners. Magnetic resonance imaging is used to confirm cerebral atrophy and, at the same time, to exclude other brain disorders, such as cerebrovascular accidents and neoplasia. Current research focuses on identifying fluid biomarkers, such as amyloid-beta, neurofilament light chain and glial fibrillary acidic protein, to support an early and objective diagnosis. The most effective management combines pharmacological therapy, targeted nutrition and non-pharmacological strategies, including environmental enrichment and behavioural support. Early intervention, ideally during mild cognitive impairment, is crucial to slow disease progression and maintain quality of life. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a high-burden, under-researched condition characterized by heterogeneous and fluctuating symptoms, including cognitive dysfunction commonly described by patients as “brain fog”. Despite growing interest in digital health technologies for symptom monitoring and personalized care, their application to the assessment and management of cognitive dysfunction in ME/CFS remains unclear. This descriptive review aimed to examine the current scientific evidence on digital approaches related to brain fog in ME/CFS. A structured literature search following PRISMA guidance was conducted to identify relevant studies. The available literature remains limited in scope and methodological maturity. During synthesizing across studies, three main functional domains of digital application become apparent: (1) digital tools for cognitive assessment, which have the strongest evidence base; (2) digital platforms for longitudinal monitoring; and (3) digitally mediated interventions or rehabilitation approaches, both of which are less well studied. Simultaneously, the findings suggest that patient-reported brain fog may represent a visible component of the broader ME/CFS disease spectrum and could serve as an early clinical indicator guiding diagnosis and management. Interpreting these symptoms within a biopsychosocial framework may facilitate understanding of the complex nature of the disease and optimize the use of digital technologies for monitoring cognitive dysfunction and supporting patient-centered care in ME/CFS. Full article

Introduction: Delirium is one of the most common and serious neuropsychiatric complications following cardiac surgery. It is associated with increased mortality, prolonged intensive care unit (ICU) and hospital stay, long-term cognitive decline, and reduced quality of life. Aims and Objectives: The aim of this study is to synthesize current evidence on the epidemiology, psychiatric and psychosocial risk factors, biological mechanisms, perioperative modifiers, prevention strategies, and long-term outcomes of delirium after cardiac surgery, with particular emphasis on its role as a marker of brain vulnerability. Materials and Methods: A narrative literature review was conducted using articles published between 1990 and 2025, identified through the PubMed and ScienceDirect databases. The search strategy included the terms “delirium,” “cardiac surgery,” “psychiatric disorders,” and “cognitive impairment.” Results: Recent evidence suggests that approximately one quarter of patients undergoing cardiac surgery develop delirium, with hypoactive forms frequently remaining underrecognized in clinical practice. Pre-existing depression, cognitive impairment, substance use disorders, low educational level, frailty, and social isolation significantly increase the risk of postoperative delirium. Within a stress–diathesis framework, peripheral physiological insults may be reflected centrally as acute brain dysfunction in vulnerable individuals. Modifiable perioperative factors include sedative choice and depth, as well as sleep and circadian disruption. Multicomponent non-pharmacological interventions, early mobilization, structured psychiatric and cognitive screening, and dexmedetomidine-based sedation have demonstrated consistent efficacy in reducing the incidence and/or duration of delirium. Furthermore, delirium has been associated with persistent cognitive and psychiatric morbidity, functional decline, and increased long-term mortality. Conclusions: Delirium following cardiac surgery is a multifactorial syndrome with significant short- and long-term consequences. A comprehensive, multidisciplinary approach integrating biological, psychiatric, and perioperative perspectives is essential for effective risk stratification, prevention, and long-term follow-up. Full article

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, multisystemic disorder characterized by severe, persistent fatigue not alleviated by rest and worsened by minimal exertion, often accompanied by post-exertional malaise (PEM), unrefreshing sleep, cognitive dysfunction, and autonomic disturbances. Despite decades of research, its pathophysiology remains incompletely understood, and skeletal muscle involvement has only recently gained attention. This review aims to provide a historical and pathophysiological synthesis of ME/CFS, emphasizing the pivotal role of skeletal muscle in the onset and persistence of symptoms, and to integrate molecular, cellular, and pathophysiological evidence into a coherent explanatory framework. This is a narrative review of published literature (1990–2025) with critical integration of clinical, biochemical, and experimental data on oxidative stress, mitochondrial dysfunction, Excitation–Contraction (E-C coupling) dysregulation, and muscle secretome alterations in ME/CFS also in relation to post-viral syndromes (e.g., Long COVID). Evidence consistently points to mitochondrial oxidative stress, redox imbalance, impaired Ca²⁺ handling, and altered signaling pathways in skeletal muscle of patients with ME/CFS. Historical milestones show an evolution from psychogenic interpretations toward recognition of ME/CFS as a biological disorder with neuromuscular and metabolic underpinnings. ME/CFS can be interpreted as a skeletal muscle–metabolic disorder characterized by oxidative distress, mitochondrial dysfunction, and impaired energy regulation, leading to the clinical picture of exercise intolerance and post-exertional malaise. Integrating basic and clinical research through a translational approach provides the foundation for new diagnostic tools, targeted therapies, and biomarkers. Full article

Visual mental imagery, the ability to generate and manipulate internal visual experiences without direct sensory input, links perception with memory, planning, and higher cognition. In this targeted narrative review, we synthesize neuroimaging and lesion evidence on the brain basis of visual imagery, with a focus on neuroradiological correlates of the ventral and dorsal visual pathways. Unlike prior cognitive neuroscience reviews that primarily emphasize functional mechanisms, this review is neuroradiology-oriented and integrates lesion patterns and white-matter disconnection to support clinico-radiological interpretation of imagery complaints. Using a dual-stream framework, we contrast ventral occipito-temporal systems that preferentially support object imagery (appearance-based features such as form, faces/objects, and color, with texture remaining under-studied) with dorsal occipito-parietal systems that preferentially support spatial imagery (relations, transformations, and navigation). Across studies, imagery recruitment is strongly task- and stage-dependent: ventral regions are most often engaged during object-focused imagery, whereas parietal regions are prominent during spatial transformation tasks, with evidence for interaction between pathways when demands require both content and spatial operations. Structural and clinico-radiological findings indicate that imagery impairment can arise from focal posterior lesions and posterior neurodegenerative syndromes but also from network disruption affecting long-range connections that support top-down access to posterior representations. Finally, emerging work on aphantasia and hyperphantasia supports a network-level view in which imagery vividness relates to how effectively higher-order systems engage visual representations. We conclude that standardized, stream-sensitive tasks and multimodal approaches combining functional and structural imaging with lesion-based evidence are key to discovering clinically actionable biomarkers of imagery dysfunction. Full article

Background/Objective: Advances in intensive care medicine have substantially improved the survival of critically ill patients; however, they have also revealed the growing burden of neurological complications that affect both short-term outcomes and long-term functioning. Neurological complications in the intensive care unit (ICU) include a wide spectrum of disorders, ranging from acute brain dysfunction such as delirium, coma, and encephalopathy to persistent cognitive impairment after discharge, which represents a key component of Post-Intensive Care Syndrome (PICS). Delirium affects approximately one-third of ICU patients and is independently associated with increased mortality, prolonged hospitalization, and worse long-term neurocognitive outcomes. Due to the limited effectiveness of pharmacological therapies, current clinical approaches emphasize prevention, early diagnosis, and non-pharmacological strategies in line with PADIS guidelines. This narrative review aims to provide a clinically relevant synthesis of neurological complications in adult ICU patients, conceptualized as a continuum from acute brain dysfunction to long-term cognitive impairment. Methods: A narrative review of the literature was conducted, focusing on studies addressing epidemiology, pathophysiology, risk factors, diagnostic strategies, and prevention of neurological complications in critically ill adults. Attention was given to delirium, ICU-acquired cognitive impairment, and their association with PICS, as well as to current guideline-based and non-pharmacological interventions. Results: Available evidence indicates that neurological complications in the ICU are multifactorial and result from the interaction between patient vulnerability, severity of illness, systemic inflammation, sedative exposure, and environmental factors. Delirium remains the most common manifestation of acute brain dysfunction and is strongly associated with adverse outcomes. Increasing evidence supports the effectiveness of structured screening, early mobilization, sleep optimization, and multidisciplinary care bundles in reducing delirium incidence and duration. Moreover, growing attention is directed toward post-ICU follow-up and rehabilitation to reduce long-term cognitive decline. Conclusions: Neurological complications should be considered a central component of critical illness and a continuum extending beyond ICU discharge. Early identification of high-risk patients, implementation of preventive strategies, and integration of acute and post-ICU care are essential to improve survival and long-term cognitive outcomes. Further research should focus on personalized preventive and neuroprotective approaches in critically ill patients. Full article

Background/Objectives: Mandarin orange peel (MOP) is rich in bioactive polymethoxyflavones, including hesperidin and nobiletin, which have shown neuroprotective effects in rodent models. However, comprehensive safety data in dogs are required to support its development as a therapeutic intervention for canine cognitive dysfunction syndrome. In this study, the safety profile of a standardized MOP formulation was evaluated in four healthy Beagle dogs. Methods: Initially, compositional analysis was performed, and 202 pesticide residues and psoralens were screened to ensure compliance with Japanese pet food safety standards. Subsequently, a dose-escalation study was conducted in which dogs received oral MOP at 2, 6, and 10 g/head/day for 3–4 weeks at each dose level. Clinical signs, hematology, and serum biochemistry were monitored throughout the study period. Results: The MOP powder composition and residue levels remained within regulatory safety limits. In the dose-escalation study, no significant dose-dependent abnormalities were observed in physical or clinicopathological parameters. One dog exhibited transient loose stools at higher doses and a temporary elevation in alkaline phosphatase levels at 2 g/head/day; however, these symptoms resolved spontaneously despite continued administration. Conclusions: MOP was safe and well tolerated in dogs even at 10 g/head/day (787–952 mg/kg/day), which is approximately five times the anticipated clinical dose. The observed fluctuations in active ingredient concentrations remained within the acceptable range for natural products and did not affect overall safety. Combined with comprehensive screening for residues, these results indicate that MOP is a high-quality and safe dietary intervention for older dogs. Full article

Mental health disorders (MHDs) and acute coronary syndromes (ACSs) demonstrate reciprocal pathophysiological connections with substantial prognostic implications. Despite robust evidence linking MHDs to adverse cardiovascular outcomes, the bidirectional relationship remains inadequately characterized in clinical practice, with limited integration of mental health screening into routine cardiac care pathways. The present narrative review comprehensively presents contemporary data on epidemiology, shared biological mechanisms, clinical consequences, and integrated management strategies across the MHD–ACS continuum. A synthesis of peer-reviewed literature, meta-analyses, observational cohorts, randomized trials, and international guideline documents was performed, focusing on depression, anxiety, post-traumatic stress disorder, bipolar disorder, schizophrenia, and suicidality in relation to ACSs. MHDs are highly prevalent in ACS populations and independently predict increased mortality, major adverse cardiac events, and poorer functional recovery. Shared mechanisms include chronic low-grade inflammation, autonomic imbalance, hypothalamic–pituitary–adrenal axis hyperactivation, platelet hyperreactivity, and endothelial dysfunction. Selective serotonin reuptake inhibitors and cognitive behavioral therapy demonstrate the strongest evidence for treating depression in cardiac populations. Collaborative, stepped-care, and integrated cardiac rehabilitation models consistently improve psychological outcomes, with variable effects on cardiovascular endpoints. MHDs and ACSs form a self-reinforcing clinical continuum. Routine mental health screening and integrated cardio-psychiatric care represent essential components of secondary prevention and long-term outcome optimization. Full article

Objective: The aim was to evaluate cochlear implantation (CI) outcomes in children with Down syndrome (DS) with severe-to-profound sensorineural hearing loss (SNHL), addressing a literature gap and discussing challenges including anatomical abnormalities, cognitive deficits, and Eustachian tube dysfunction. Data Sources: Systematic searches were conducted in PubMed, Web of Science, Scopus, and Embase from inception through to June 2025. Review Methods: A systematic review adhering to PRISMA guidelines was performed. Included studies reported CI outcomes in DS patients receiving otolaryngologic care for SNHL. Extracted data included findings on ear anatomy, auditory performance, speech/language development, intelligibility, and duration of CI use. Results: A total of 149 abstracts were screened, yielding six studies with 26 patients that met the inclusion criteria. The review included pediatric DS patients with documented ages at implantation spanning from 11 months to 17.9 years. CI provided significant benefits for DS patients, including improved audiometric results, enhanced environmental awareness, and psychosocial gains. Optimal outcomes were associated with early implantation, thorough preoperative imaging (CT/MRI), and management of middle ear disease. Variability in outcomes often reflected cognitive limitations and anatomical challenges such as cochlear nerve hypoplasia and Eustachian tube dysfunction. Conclusions: CI can significantly improve quality of life and communication in children with DS when tailored to their unique needs. Preoperative imaging is essential to assess candidacy, and middle ear disease should be addressed prior to surgery. Clinicians should counsel families with individualized goals that emphasize functional hearing gains over normative speech benchmarks. Broader adoption of CI in this population may be supported by standardized, population-sensitive outcome measures and future prospective studies. Full article

Eating disorders (EDs) disproportionately affect women and are associated with substantial morbidity, chronicity, and mortality. While established psychological models focus on the content of maladaptive cognitions related to body weight, shape, and eating behaviors, growing evidence suggests that additional process-level mechanisms contribute to symptom persistence and treatment resistance. Metacognitive models emphasize how individuals relate to their thoughts, emotions, and internal experiences, highlighting maladaptive beliefs about thinking and the resulting cognitive–attentional patterns (e.g., repetitive negative thinking, self-focused attention, and inflexible attentional control) as potential maintaining factors across psychopathology. This narrative review synthesizes the theoretical and empirical literature on metacognitive dysfunction in EDs, with a focus on mechanisms that may be particularly relevant for women. We integrate epidemiological data and gender-sensitive frameworks, and review evidence on metacognitive beliefs and cognitive–attentional syndrome (CAS)-related processes across anorexia nervosa, bulimia nervosa, and binge-eating disorder. Overall, studies indicate that dysfunctional beliefs about the uncontrollability and danger of thoughts, alongside perseverative cognitive styles, are associated with greater ED symptom severity. We discuss diagnosis-relevant patterns as clinically useful heuristics, interactions with sociocultural and emotional vulnerability factors, and implications for assessment, treatment integration, and prevention. The evidence base is largely correlational and derived from predominantly female samples, underscoring the need for longitudinal research and studies that explicitly test sex/gender as a moderator. Full article

Irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) share symptoms such as abdominal pain, bloating, and altered bowel habits. Both are linked to dysbiosis and gut–brain axis dysfunction. IBS is a multifactorial disorder characterized by abnormal motility, visceral hypersensitivity, low-grade inflammation, and alterations in the microbiota. In contrast, SIBO is defined by excessive bacterial colonization of the small intestine that can mimic or worsen IBS symptoms. Gut microbes and their metabolites influence motility, immune activation, barrier integrity, and gas production; methanogen overgrowth is associated with constipation-predominant presentations, while hydrogen- and hydrogen sulfide-related pathways may contribute to diarrhea and bloating. Because recurrent or empiric antibiotic use is common—particularly in suspected SIBO—yet carries risks of resistance, microbiome disruption, and relapse, there is a strong rationale to prioritize effective non-antibiotic strategies. Accordingly, this review synthesizes current evidence on IBS/SIBO pathophysiology and microbiota interactions. It evaluates non-pharmacological interventions including dietary approaches, probiotics/prebiotics, herbal therapies, and mind–body treatments (e.g., cognitive behavioral therapy and gut-directed hypnotherapy). We emphasize an integrative framework that supports symptom control and quality of life while helping reduce unnecessary antibiotic exposure. Full article