Worldwide epidemiological data indicates insufficient diagnosis of diabetes as an increasing problem of public health. Searching for solutions in this disadvantageous situation, occupational medicine health services seem to open up a unique opportunity to recognize some abnormalities in early steps, especially among the asymptomatic working-age population. 316 workers underwent obligatory prophylactic examinations. In patients with twice assayed FGL ≥ 126 mg/dl (7.0 mmol/l) the additional intervention was implemented, including further diagnostic process and therapy in General Practice (GP), followed by examination by an occupational health specialist within 3 months. The diagnosis of previously unknown diabetes was established among 2.5% of examined workers. All patients referred to the GP due to detected glycaemia impairment visited their doctor and finished the diagnostic process, took up therapy constrained by the occupational health physician to show the effects of intervention within 3 months. Prophylactic medical check-ups allow improved compliance and medical surveillance over glycaemia impairment in patients with prediabetes states, unknown diabetes or uncontrolled clinical course of diabetes. Considering fasting glucose level during mandatory prophylactic examination helps effective prevention of diabetes and its complications and thus give public health system benefits.

IBD, encompassing CD and UC, are characterized by chronic gastrointestinal inflammation due to abnormal immune responses to gut microflora. The bidirectional communication between the gut and the brain, known as the GBA, is disrupted in IBD, leading to neurobiological imbalances and affective symptoms. Systemic inflammation in IBD affects the brain's inflammatory response system, hormonal axis, and BBB integrity, influencing gut microbiota and clinical responses to probiotics. This review aims to explore the links between dysregulations in the GBA, serum biomarkers, and the development of MCI and NDDs. The objective is to identify potential correlations and propose future research directions to understand the impact of altered microbiomes and intestinal barrier functions on NDDs. Studies suggest a potential link between IBD and extraintestinal complications such as MCI and NDDs. Mechanisms include systemic inflammation, BBB dysfunction, autoimmune responses, GBA dysfunction, medication effects, and comorbidities. Serum biomarkers, including vitamin D3, C-reactive protein, high-sensitivity C-reactive protein, vitamin B12, homocysteine, serum amyloid, neuron-specific enolase, neurofilament light chain, S100 proteins, brain-derived neurotrophic factor, IL-6, LP-2 associated phospholipase, prostaglandin E2, IL-1β, and TNF-α, have been investigated for their potential to predict MCI but current results are lacking clarity.

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating muscle mass reduction seen in sarcopenia and the decline of neuronal functions characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review ana-lyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on ox-idative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sar-copenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, in-flammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient out-comes. This study emphasizes the complex interplay between vascular dysfunction, muscle de-generation, and cognitive decline, highlighting the necessity for multidisciplinary treatment ap-proaches. Advances in this domain promise improved diagnostic accuracy, more effective thera-peutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.

Alzheimer’s disease (AD) poses a significant public health challenge due to its irreversible and progressive nature while lack of a cure. As a potential strategy to combat AD, its prevention becomes increasingly attractive. Mild Cognitive Impairment due to AD (MCI-AD) represents a critical transitional stage between normal age-related cognitive decline and more severe AD conditions, occurring just before dementia onset. Unfortunately, there is currently no established animal model that accurately recapitulates MCI-AD characteristics. While many laboratories have traditionally used normally aged wild-type animals as experimental models, this approach falls short in representing the inherently worse state of MCI-AD compared to normal aging. To address this gap, we introduce an animal model—a transgenic mouse line with genetic inactivation of G protein-coupled receptor kinase-5 (GRK5), commonly known as the GRK5 knockout (GRK5KO) mouse. These GRK5KO mice exhibit amnesia, cognitive deficits, increased β-amyloid levels, neurofibrillary tangle (NFT) immunopositive axonopathy, and hippocampal neurodegenerative changes. Importantly, these pathological alterations predominantly impact the entorhinal, transentorhinal, and hippocampal cortices, aligning with human MCI-AD criteria and Braak stage II of human AD progression. Notably, female GRK5KO mice show approximately 2.5 times more NFT-positive axonopathy than males, mirroring the higher prevalence of AD cases in women. Collectively, existing data strongly supports the GRK5KO mouse as a qualified animal model for studying MCI-AD.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

Hearing impairment (HI) is a common sensory disorder that is defined as the partial or complete inability to detect sound in one or both ears. This diverse pathology is associated with a myriad of phenotypic expressions and/or syndromes. HI can be caused by various intrinsic, environmental and/or unknown factors. Some ontologies capture some relevant HI forms, phenotypes and syndromes, but there is no comprehensive knowledge portal which includes aspects specific to the HI disease state. This hampers inter-study comparability, integration and interoperability within and across disciplines. This work describes the HI Ontology (HIO) that was developed based on the Sickle Cell Disease Ontology (SCDO) model. This is a collaboratively developed resource built around the 'Hearing Impairment' concept by a group of experts in different aspects of HI and ontologies. HIO is the first comprehensive, standardized, hierarchical and logical representation of existing HI knowledge. HIO allows researchers and clinicians alike to readily access standardized HI-related knowledge in a single location and promote collaborations and HI information sharing, including epidemiological, socio-environmental, biomedical, genetic and phenotypic information. Furthermore, this ontology illustrates the adaptability of the SCDO framework for use in developing a disease-specific ontology.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

The intricate interplay between driver cognitive dysfunction, mental workload (MWL), and heart rate variability (HRV) provides a captivating avenue for investigation within the domain of transportation safety studies. This article presents a comprehensive review and examines cognitive hindrance stemming from mental workload and heart rate variability. It scrutinizes the mental workload experienced by drivers by leveraging data gleaned from prior studies that employed heart rate monitoring systems and eye tracking technology, thereby illuminating the correlation between cognitive impairment, mental workload, and physiological indicators such as heart rate and ocular movements. The investigation is grounded in the premise that the mental workload of drivers can be assessed through physiological cues, such as heart rate and eye movements. The study discovered that heart rate variability (HRV) and infrared (IR) measurements played a crucial role in evaluating fatigue and workload for skilled drivers. However, the study overlooked potential factors contributing to cognitive impairment in drivers and could benefit from incorporating alternative indicators of cognitive workload for deeper insights. Furthermore, investigated driving simulators demonstrated that an eco-safe driving Human-Machine Interface (HMI) significantly promoted safe driving behaviors without imposing excessive mental and visual workload on drivers. Recommendations were made for future studies to consider additional indicators of cognitive workload, such as subjective assessments or task performance metrics, for a more comprehensive understanding.

We propose that a dietary reduction of Lipopolysaccharide (LPS) could reduce risk and slow the progression of cognitive decline and Alzheimer’s disease. LPS is a component of the highly inflammatory cell membrane of Gram-negative bacteria. The highest dietary sources of LPS are processed meat and dairy products, which can sharply raise plasma LPS within one to two hours. The LPS in these foods is packaged into chylomicrons, which enter the bloodstream. Smaller amounts of LPS from colonic microbiota do not account for the sharp postprandial increase of plasma LPS. Once in the bloodstream, LPS can trigger the release of inflammatory cytokines within three hours. LPS can increase cytokines via LPS binding protein and cluster of differentiation-14, triggering toll-like receptor-4, and activating nuclear factor kappa-B. Nuclear factor kappa-B can increase cytokine levels, including interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha. LPS and inflammatory cytokines are higher in Alzheimer’s disease, both in plasma and in the central nervous system. These cytokines can enter the brain via active transport and induce microglial activation and inflammatory damage in the brain, including loss of synapses and neurons. Elevated brain inflammation from dietary LPS can contribute to cognitive impairment and increased risk of dementia.

Background. Amyotrophic Lateral Sclerosis (ALS) is a devastating disease involving motor neuron degeneration. The few drugs approved for treatment have at most a marginal benefit, and death usually occurs 2-5 years after diagnosis. Methods. A thorough manual examination of the relevant literature, covering over 35,000 papers. Results. Two major phenomena that are generally not known to clinicians were found. First, insulin signaling is impaired in ALS even in patients not diagnosed with diabetes (DB). Almost all studies that have explicitly tested insulin function in non-DB ALS patients using glucose tolerance tests (18 out of 20, 1964-2022, different groups) have found it to be impaired. Second, there is strong evidence for excessive insulin-independent glucose uptake (IIGU) in ALS. In addition, (i) early/late diabetes are associated with increased/decreased risk, respectively; (ii) insulin-based diabetes drugs are protective in ALS in large retrospective human studies; and (iii) strong animal and human evidence shows that insulin opposes all of the major pathological processes in ALS. Conclusion. Most ALS patients have insulin impairment, yet this is commonly not diagnosed, likely because excessive IIGU normalizes glucose levels. The impairment promotes disease progression. Late diabetes is associated with decreased risk because high glucose levels indicate non-excessive IIGU, and because diabetes drugs are protective. Insulin-based treatment (e.g., GLP1 agonists, insulin) is beneficial and can be disease-modifying in ALS and in frontotemporal dementia variants comorbid with ALS. ALS patients should be routinely tested for insulin function and treated if test results are positive.

Introduction: Periodontitis is a severe oral infection that can contribute to systemic inflammation. A large body of evidence suggests a role for systemic inflammation in the initiation of neurodegenerative disease. This systematic review synthesized data from observational studies to investigate the association between periodontitis and neuroinflammation in adults. Methods and materials: A systematic literature search of PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) was performed for studies published from the date of inception up to September 2021. Search terms for the exposure “oral disease” and outcome “dementia”, “neuroinflammation” and “cognitive decline” were used. Study selection and data extraction were independently undertaken by two reviewers. The final eligible articles were included only if the exposure is periodontitis and the outcome is cognitive impairment or dementia or a topic related to this condition, and if the study was conducted in an adult population. The quality and risk of bias were assessed by Newcastle Ottawa Scale (NOS). Qualitative synthesis was used to narratively synthesize the results. Six cohort studies, three cross-sectional studies, and two case-control studies met the inclusion criteria. These eleven studies were only narratively synthesized. Meta-analysis was not performed due to the methodological heterogeneity of the studies. Results: All the included studies show evidence of an association between periodontitis and cognitive im-pairment or dementia and Alzheimer’s disease pathology. Conclusion: Nonetheless, the mechanisms responsible for the association between periodontitis and dementia are still unclear.

The National Institute of Health Stroke Scale (NIHSS) is used worldwide to classify stroke severity as ‘mild’, ‘moderate’ or ‘severe’ based on neurological impairment. Yet stroke survivors argue that the classification of ‘mild’ does not represent the holistic experience and impact of stroke on their daily lives. In this observational cohort study, we aimed to identify different types of impairment among stroke survivors classified as mild. We used mild stroke survivors’ data from the START longitudinal stroke cohort (n=73) with measures related to sensorimotor, cognition, depression, functional disability, physical activity, work and social adjustment over 12 months. Given the multi-source, multi-granular and unlabelled nature of data, we utilised a structure-adapting, unsupervised machine learning approach, the Growing Self-organising Map (GSOM) algorithm to generate distinct clinical profiles. These diverse impairment profiles revealed that mild stroke survivors experience varying degrees of impairment and impact (cognitive, depression, physical activity, work/social adjustment) at different time points, despite the uniformity implied by their NIHSS-classified ‘mild’ stroke. This emphasises the necessity of creating a holistic and comprehensive representation of mild stroke survivors’ needs over the first-year post-stroke to improve rehabilitation and post-stroke care.

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard ratios or odds ratios) are determined for incidence for participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below or above specified values. Serum 25(OH)D concentrations vary over time, thereby diluting the effect of 25(OH)D for long follow-up periods. Inverse relationships between RR and follow-up period have been reported for all-cause mortality rate and cancer incidence rates. Here I evaluate the effect for neurological outcomes. Methods: I analyzed how follow-up period affected results from 10 cohort studies of all-cause dementia, 6 studies of Alzheimer’s disease, and 9 for cognitive impairment with respect to vitamin D deficiency. Results: For all-cause dementia, Alzheimer’s disease, and cognitive impairment, respectively, the linear regression fits are RR = 2.9 – 0.14 × years, r = 0.73, p = 0.02; RR = 2.9 – 0.14 × years, r = 0.69, p = 0.13; and RR = 1.8 – 0.066 × years, r = 0.72, p = 0.03. The regression fit to RR for the shortest follow-up period for each outcome is considered the best estimate of vitamin D deficiency’s effect on risk. Those values are approximately twice that found by averaging all RRs without considering the effect of follow-up period. Conclusions: Vitamin D’s effect on risk of neurological conditions should be determined with relatively short follow-up periods after repeated 25(OH)D measurements as warranted during follow-up.

Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently growing number of preclinical studies has revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among other. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)-kynurenine (KYN) metabolic system, which observably contributes to development of pathological conditions including neurological and psychiatric disorders. This narrative review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases.

Technology-based approaches for upper limb (UL) motor rehabilitation after stroke are designed mostly for severely affected patients to increase their recovery chances. However, the available randomised controlled trials (RCTs) focused on efficacy of technology-based interventions often include patients with a wide range of motor impairment. This scoping review aims at overviewing the actual severity of stroke patients enrolled in RCTs which claim to specifically address UL severe motor impairment. The literature search was conducted on Scopus and PubMed databases and included articles from 2008 to May 2024, specifically RCTs investigating the impact of technology-based interventions on UL motor functional recovery after stroke. Forty-eight studies were selected. They showed that upon patients’ enrolment the values of the UL Fugl-Meyer Assessment and Action Research Arm Test covered the whole range of both scales, thus revealing the non-selective inclusion of severe impaired patients. Heterogeneity in terms of numerosity, characteristics of enrolled patients, trial design, implementation, and reporting were present across studies. No clear difference in the severity of the included patients according to the intervention type was found. Patient stratification upon enrolment is crucial to best direct resources to those patients who will benefit the most from a given technology-assisted approach (personalised rehabilitation).

Brain pathological changes impair cognition early in disease etiology. There is an urgent need for understanding aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2, also named Fus1, is a mitochondrial-resident protein regulating Ca2+ fluxes to and from mitochondria impacting overall health. We reported that Tusc2-/- female mice develop chronic inflammation and age prematurely, causing age- and gender-dependent spatial memory deficits at 5 m.o. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2-/- female mice demonstrated proinflammatory increase in astrocytes, IFN-γ expression in CD4+T cells and Granzyme-B in CD8+T cells. We also found fewer FOXP3+ T-regulatory cells and Ly49G+ NK and Ly49G+ NKT cells in female Tusc2-/- brain, suggesting a weakened anti-inflammatory response. Moreover, Tusc2-/- hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2+ dynamics. Overall, data suggest that dysregulation of Ca2+-dependent processes and proinflammatory brain microenvironment heighten in Tusc2-/- mice could underlie cognitive impairment. Thus, strategies to modulate the brain’s Tusc2-, Ca2+, and mitochondria-dependent pathways should be explored to improve cognitive health.

Background: In recent years, the integration of robotic systems into various aspects of daily life has become increasingly common. As these technologies continue to advance, ensuring user-friendly interfaces and seamless interactions becomes more essential. For social robots to genuinely provide lasting value to humans, a favourable user experience (UX) emerges as an essential prerequisite. Aim: This article aimed to evaluate the usability of the MINI robot, highlighting its strengths and areas for improvement based on user feedback and performance. Method: In a controlled lab setting, a mixed-method qualitative study was conducted with ten individuals aged 65 and above diagnosed with mild dementia (MD) and mild cognitive impairment (MCI). Participants engaged in individual MINI robot interaction sessions, completing cognitive tasks as per written instructions. Video and audio recordings documented interactions, while post-session System Usability Scale (SUS) questionnaires quantified usability perception. Ethical guidelines were followed, ensuring informed consent, and the data underwent qualitative and quantitative analyses, contributing insights into the MINI robot's usability for this demographic. Results: The study addresses the ongoing challenges that tasks present, especially for MD individuals, emphasizing the importance of user support. Most tasks require both verbal and physical interactions, indicating that MD individuals face challenges when switching response methods within subtasks. These complexities originate from the selection and use of response methods, including difficulties with voice recognition, tablet touch, and tactile sensors. These challenges persist across tasks, with individuals with MD struggling to comprehend task instructions and provide correct answers and individuals with MCI struggling to use response devices, often due to the limitations of the robot's speech recognition. Technical shortcomings have been identified. The results of the System Usability Scale (SUS) indicate positive perceptions, although there are lower ratings for instructor assistance and pre-use learning. The average SUS score of 68.3 places device usability in the "good" category. Conclusion: Our study examines the usability of the MINI robot, revealing strengths in quick learning, simple system and operation, and integration of features while also highlighting areas for improvement. Careful design and modifications are essential for meaningful engagement with people with dementia. The robot could better benefit people with MD and MCI if clear, detailed instructions and instructor assistance are available.

Norepinephrine plays an important role in modulating memory consolidation and evocation through its beta-adrenergic receptors (Adrβ: β1, β2 and β3), which are expressed in the hippocampus (HC) and amygdala (AMY). Here we hypothesized that multisensory stimulation would reverse the memory impairment caused by the inactivation of the Adrβ3 with consequent inhibition of sustained glial-mediated inflammation and glutamatergic depuration. To test this, 21- and 86-day-old Adrβ3KO mice and respective controls underwent to (i) gustative and olfactive stimuli of positive and negative valence associated with (ii) intellectual challenges to reach the food in addition to (iii) objects in hidden places (iv) foraging for 8 weeks followed by (v) analysis of GFAP, Iba-1 and EAAT2 protein expression in the HC and AMY. While this protocol restored the memory impairment when applied to Adrβ3KO animals immediately after weaning, it had no effect when applied to adult animals. In fact, we observed that aging worsens the memory of Adrβ3KO mice. Although no significant expression of GFAP and Iba1 were observed in HC of young and old mice, Adrβ3KO increased EAAT2 expression HC of old mice, while MS didn’t change EAAT2 in young mice but enhanced it expression in older. Relative to AMY of old mice Adrβ3KO increased GFAP expression compared whit WT mice and MS sustained the GFAP expression and increased the EAAT2 expression compared with WT group. These results suggest that a richer and more diverse environment helps to correct memory impairment when applied right after weaning Adrβ3KO animals, also show that the changes in GFAP, Iba1 and EAAT2 expression levels in young and old mice indicate a functional significance in the process of learning and memory and that the control of neuroinflammation in limbic areas mediates this response. They also reinforce the idea that disruption of noradrenergic signaling could be involved in the cognitive impairment observed later in life.

Increased activity of transforming growth factor-beta (TGF-β) is a key factor mediating kidney impairment in diabetes. Glomerular podocytes, the crucial component of the renal filter, are a direct target of TGF-β action, resulting in irreversible cell loss and progression of chronic kidney disease (CKD). Urolithin A (UA) is a member of the family of polyphenol metabolites produced by gut microbiota from ellagitannins and ellagic acid-rich foods. The broad spectrum of biological ac-tivities of UA makes it a promising candidate for the treatment of podocyte disorders. In this in vitro study, we investigated whether UA influences the changes exerted in podocytes by TGF-β and high glucose. Following a 7-day incubation in normal (NG, 5.5 mM) or high (HG, 25 mM) glucose the cells were treated with UA and/or TGF-β1 for 24 hours. HG and TGF-β1, each independent and in concert reduced expression of nephrin, increased podocyte motility and up-regulated expression of b3 integrin and fibronectin. These typical for epithelial-to-mesenchymal transition (EMT) effects were inhibited by UA in both HG and NG conditions. UA also reduced the typically elevated in HG expression of TGF-β receptors and activation of TGF-β signal transducer Smad2. Our results indicate that in podocytes cultured in conditions mimicking diabetic milieu, UA inhibits and reverses changes underlying podocytopenia in diabetic kidneys. Hence, UA should be considered as a po-tential therapeutic agent in podocytopathies.

(1) Background The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated applying data from older cognitively healthy adults living in the US, Ireland and Australia (the norming sample) The study has two aims: to establish valid cut-offs for distinguishing between no cognitive impairment, mild cognitive impairment (MCI) and dementia (1), and to cross-validate the new norms for detecting MCI and dementia (2) in a community sample of older adults with clinical diagnoses; (2)Methods: The validation sample included 142 older adults (mean age=87.7, SD=3.55) from the Sydney Memory and Aging Study (MAS Study). Participants were classified as having normal cognition, MCI, or dementia through a consensus diagnosis as well as by the SKT; (3)Results: The sensitivity of the SKT for the differentiation of cognitive impairment (MCI or dementia) from normal cognition was 80.6%. The convergence between the SKT and the consensus diagnoses was 60.1% for all three diagnostic groups. The correlation between the SKT and the Addenbrooke’s Cognitive Examination III (ACE-III), a well validated measure of cognitive ability in older adults, was r = 0.3;. (4) Conclusions: In sum, it can be stated that the SKT is a valid tool for detecting early stages of cognitive impairment, performing very well in discriminating between no cognitive impairment and cognitive impairment (MCI or dementia).

Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits, often associated with the development of neurodegenerative diseases. The formation of reactive oxygen species (ROS) and oxidative stress have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice, we observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus). This elevation was accompanied by astrogliosis, microgliosis and the accumulation of amyloid precursor protein (APP). Concurrently, r-mTBI mice displayed impaired motor learning and spatial memory deficits. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as gliosis, oxidative stress, axonal damage, and white matter damage. These findings underscore the role of NHE1 upregulation in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 as a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.

Background: Epileptic patients frequently encounter cognitive impairment. Functions that are mostly affected involve memory, attention and executive function; however this is mainly dependant on the location of the epileptic activity. The aim of the study is to assess cognitive functions in MRI-negative epilepsy patients by means of neurophysiological and neuropsychological measures. Methods: The patients were enrolled from the outpatient Epilepsy/Clinical Neurophysiology clinic over a time period of 6 months. The study sample comprised 20 MRI negative epilepsy patients [mean age ± standard deviation (SD), 30.3 ± 12.56 years; age range 16-60 years; average disease duration, 13.95 years) and 10 age-matched controls (mean age ± SD, 24.22 ± 15.39 years), that were also education-matched (p>0.05) Patients with epileptogenic lesions were excluded from the study. Informed consent was obtained from all subjects involved in the study. Auditory ERPs and the cognitive screening tool EpiTrack, were administered to all subjects. Results: Latencies of P300 and slow waves were prolonged in patients compared to controls (p<0.05). ASM load and the patients’ performance in the EpiTrack maze subtest were the most significant predictors of P300 latency. A decline in memory, attention, and speed of information processing has been observed in patients with cryptogenic epilepsy compared to age-matched controls, as reflected by P300 latency and EpiTrack scores.

Oligodendrocytes are myelinating cells of the central nervous system, which are generated by progenitor oligodendrocytes as a result of maturation processes. The main function of mature oligodendrocytes is to produce myelin, a lipid-rich multi-lamellar membrane that wraps tightly around neuronal axons, isolating them and facilitating nerve conduction through saltatory propagation. The myelination process requires the consumption of a lot of energy and a high metabolic turnover. Mitochondria are essential organelles which regulate many cellular functions including the energy production through oxidative phosphorylation. Any mitochondrial dysfunction impacts cellular metabolism and negatively affects the health of the organism. If the functioning of the mitochondria is unbalanced the myelination process is impaired. At the end of myelination, oligodendrocytes synthesize about 40% of the total lipids present in the brain. Since lipid synthesis occurs in the cellular endoplasmic reticulum, the alteration of this organelle can lead to partial or deficient myelination, triggering numerous neurodegenerative diseases. In this review the main dysfunctions of oligodendrocytes caused by exogenous or endogenous stimuli will be investigated. Furthermore, the oligodendrocyte reactions to excessive mitochondrial oxidative stress and an altered regulation of the functioning of the endoplasmic reticulum will be discussed.

Background: Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods: In this randomized controlled trial 55 patients with MCI were randomized into a sportive dance training (IG; n=26; Age: 70.7 +/- 5.6 years; 62% female) or an inactive control group (CG; n=24; Age: 69.1 +/- 6.8 years; 46% female).The dance group received two 90-minute dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heartrate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength and heart rate variability (HRV). Results: We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO2max) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength although not statistically significant. HRV displayed a nonsignificant decrease following the intervention. Conclusion: The results of this randomized controlled trial suggest that sportive dance training can preserve physical fitness in older adults with MCI. Although improvements in the other parameters were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence.

Background: Cancer-related cognitive impairment (CRCI) is one of the most serious side effects of cancer that negatively impact the quality of life of cancer patients and survivors. There is evidence of CRCI in Hodgkin lymphoma patients (HL); however, there is a lack of studies examining the presence of cognitive deficits before starting any treatment in HL patients. Methods: Forty patients (N=40) newly diagnosed with HL (with no previous cancer diagnoses) and 40 healthy controls (N=40) matched for age, sex, education, and premorbid intellect completed the neuropsychological battery and subjective and objective measures of affective distress and quality of life. Results: The results showed impairment in three out of six cognitive domains: verbal memory and learning, speed of processing/ psychomotor speed, and abstraction/executive functions in the HL patients before the initiation of any treatment. Speed of processing/psychomotor speed domain negatively correlated with depression. Conclusion: Impairment in verbal memory and learning and abstraction/executive functions domains in HL patients seems to occur before the initiation of treatment independently of anxiety, depression, or physical symptoms. This suggests that HL itself may cause cognitive deficits in these cognitive domains. However, the underlying causes of CRCI still remain unclear.

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

A 47-year-old physician suddenly noticed a persistent difficulty maintaining attention. He was awake, alert, and oriented. After two hours he developed fever, ageusia, and anosmia. He denied any previous history of psychiatric illness and was hydrated at the time of the subjective attention impairment. On admission, the patient remained oriented. He reported the persistence of attention problems, anosmia, and mild fatigue. The oxygen saturation 99% while he was breathing ambient air. Laboratory tests were unremarkable. A high-resolution computed tomography of the chest was normal. Nasopharyngeal and throat swabs specimens on reverse transcription-polymerase chain reaction analysis tested positive for SARS-CoV2. On illness day 3, the examination was unchanged, but he continued to complain of difficulties to stay focused. Then, he performed an objective attention test. The test demonstrated a moderate attentional impairment. On day 6, the patient reported a subjective worse in his concentration and performed a second test. Although his physical examination remained normal, the attention performance was worse as compared to day 3. Eight hours after worsening of attention impairment, the patient’s oxygen saturation dropped to 94%. From illness days 9 to 14, the patient evolved with clinical improvement. On day 10, a third objective attention test indicated a mild deficit. On day 16, he did not report any other symptom and the attention test was completely normal. Then, the patient returned to work. Neurological symptoms had been previously described in COVID- 19 patients. However, no previous research had investigated early cognitive deficits preceding the traditional symptoms.

(1) Background. Cognitive impairment in people with Multiple Sclerosis (MS) has been studied in relation to some clinical variables (e.g., motor disability and disease duration) and lifestyle fac-tors such as Cognitive Reserve (CR). However, only very few studies have considered the interac-tion of clinical variables and cognitive reserve in preserving the integrity of the neuropsychologi-cal profile. In this paper, we hypothesised that a higher level of CR might predict good cognitive efficiency by modulating the clinical outcome of the disease. (2) Methods. A sample of 100 partic-ipants with MS (age range 30-74), was recruited and assessed remotely with a questionnaire to measure CR and a cognitive screening test. Data were analysed through Generalized Additive Models. (3) Results. We found that the model analysing the interaction between CR and disease duration, and between CR and motor disability was able to explain a significant percentage of cognitive performance. In particular, higher levels of CR predicted better cognitive performance despite long disease duration, unless the motor disability was severe. (4) Conclusion. This study highlights the crucial role of CR in modulating cognitive efficiency in people with MS.

This study aims to systematically review and meta-analyze the nitro-oxidative stress (O&NS)/antioxidant (ANTIOX) ratio in the peripheral blood of people with mild cognitive impairment (MCI). We searched PubMed, Scopus, Google Scholar, and Web of Science for articles published from inception until July 31, 2021. Forty-six studies on 3.798 MCI individuals and 6.063 healthy controls were included. The O&NS/ANTIOX ratio was significantly higher in MCI than in controls with a Standardized Mean Difference (SMD)=0.378 (95% CI: 0.250; 0.506). MCI individuals showed increased lipid peroxidation (SMD=0.774, 95%CI: 4.416; 1.132) and O&NS-associated toxicity (SMD=0.621, CI: 0.377; 0.865) and reduced glutathione (GSH) defenses (SMD=0.725, 95%CI: 0.269; 1.182) as compared with controls. MCI was also accompanied by significantly increased homocysteine (SMD=0.320, CI: 0.059; 0.581), but not protein oxidation, and lowered non-vitamin (SMD=0.347, CI: 0.168; 0.527) and vitamin (SMD=0.564, CI: 0.129; 0.999) antioxidant defenses. The results show that MCI is at least in part due to increased neuro-oxidative toxicity and suggest that treatments targeting lipid peroxidation and the GSH system may be used to treat or prevent MCI.

Since the water-borne iodine excessive goiter was firstly found and reported in 19 in Hebei Province, it was confirmed successively. The national water-borne investigation carried out in 2005 demarcated the water-borne iodine excess areas and water-borne iodine excess endemial areas. The high iodine water well was found In 129 counties of 11 provinces, about 30.98 million people of threatened population lived in water-borne iodine excess areas and water borne iodine excess endemial areas. In these areas, the measures of prevention and control was effectively implemented. In 2016, the new standard of iodine excess area was issued, the iodine excess areas redrawed, and in these areas, non-iodized salt should be supplied and the drinking water should be gradually improved of water, and to control the damage of water-borne iodine excess at an early date

Objectives: To develop and validate the Communities Geriatric Mild Cognitive Impairment Risk Calculator (CGMCI-Risk), aimed at aiding community healthcare workers in the early identification of individuals at high risk of Mild Cognitive Impairment (MCI); Methods: Based on nationally representative community survey data, backward stepwise regression was employed to screen the variables, and logistic regression was utilized to construct the CGMCI-Risk. Internal validation was conducted using bootstrap resampling, while external validation was performed using temporal validation. The area under the receiver operating characteristic curve (AUROC), calibration curve, and decision curve analysis (DCA) were employed to evaluate the CGMCI-Risk in terms of discrimination, calibration, and net benefit, respectively; Results: The CGMCI-Risk model included variables such as age, educational level, sex, exercise, garden work, TV watching or radio listening, Instrumental Activity of Daily Living (IADL), hearing, and masticatory function. The AUROC was 0.781 (95% CI = 0.766 to 0.796). Calibration curve showed strong agreement, and the DCA suggested substantial clinical utility. In external validation, the CGMCI-Risk model maintained similar performance with an AUROC of 0.782 (95% CI = 0.763 to 0.801); Conclusions: CGMCI-Risk is an effective tool for assessing cognitive function risk within the community. It uses readily predictor variables, allowing community healthcare workers to identify the risk of MCI in older adults over a three-year span.

In Switzerland, psychomotor therapy (PMT) is a standard treatment for children with graphomotor impairments, but scientific evidence of its effectiveness is rare. To investigate the effectiveness of PMT, we conducted a randomized field trial (RFT). The sample consisted of 121 first and second graders with graphomotor impairments, some of whom met the criteria of developmental coordination disorder, while the remaining suffered from developmental dysgraphia. The treatments lasted over 5 months. Handwriting fluency and consistency were measured five times on a digitizing tablet. All participating children completed a self-concept interview, and a standardized fine motor performance test twice. Psychomotor therapy significantly improved the fine motor skills of the therapy group compared to those of the waiting group. However, there was no evidence that the treated children improved more than the waiting children in terms of their graphomotor skills such as frequency, automaticity, and consistency of forming letters. Finally, the children of the therapy group showed partial improvements in their handwriting self-concept, while those of the waiting group children remained stable. This short-term RFT demonstrated the effectiveness of PMT in terms of fine motor skills and some aspects of the handwriting self-concept but showed no effects on handwriting fluency and consistency.

Detecting and evaluating pain in people with cognitive impairment, especially dementia, is a challenge. Their ability to accurately report pain and comprehend related questions decreases the reliability of their self-report. This has contributed to the fact that pain is underdiagnosed and undertreated in this population, which can lead to involuntary ageism. The design and assessment of this training capsule under the context of the European COST-Action TD1005 responds to the need for education and training in "Pain Assessment In Cognitive Impairment, especially dementia" and the development of the internationally agreed observational PAIC15 scale. The 3-hour capsule, intended for healthcare workers and caregivers, consists of theoretical-practical levels: 1) basic concepts and challenges in pain in aging, cognitive impairment/dementia, 2) available scales and PAIC15, 3) video presentation of clinical cases illustrating a 3×2 matrix of situations (rest, transfer and experimental pain) and stages of disease (mild and moderate). The objectives focused on training the ability to observe, detect, and assess the signs of pain using PAIC15 and its feasibility. The pre-post analysis in a Master educational setting showed agreement with the results obtained in the Spanish national survey on 1) scarce knowledge of observational tools and their use, and 2) uncertainty in the identification of signs of pain and feasibility in moderate/severe scenarios. The capsule improved the ability to identify and evaluate the pain items, especially facial expressions, and their confidence on observational tools. Debriefings highlighted the relevance of observational scales in dementia and the gain obtained using the new observational instrument.

The time when a patient has mild cognitive impairment (MCI) is an important period for delaying the onset of dementia and has been the main target of dementia prevention research in recent years. The purpose of this study was to investigate the dietary intake and dietary patterns of MCI patients in Taiwan. In total, 40 subjects were enrolled in this cross-sectional study that was conducted from July 2019 to September 2021 at Linkou Chang Gung Memorial Hospital. Results of the clinical dementia rating (CDR) and mini-mental state examination (MMSE) were obtained from medical records. Participants were divided into two groups: a healthy group (MMSE ≥ 26 points, CDR=0) and an MCI group (MMSE ≥ 26 points, CDR=0.5). Results indicated that the MCI group had significantly higher copper and lower low-fat meat intake compared to the healthy group. Furthermore, the high MIND (Mediterranean-dietary approaches to stop hypertension intervention for neurodegenerative delay) diet score represented a lower risk of MCI. After adjusting for age and gender in the multivariate regression analysis, calcium and fruit intake levels were positively associated with the MMSE. In conclusion, the prevalence of MCI was closely associated with dietary intake, such as copper and calcium, as well as dietary patterns, particularly the MIND diet.

Background: Assessment and management of pain in elderly people with cognitive impairment is particularly challenging. Physiological changes due to aging as well as comorbidities and polypharmacy are responsible for a complex clinical approach. Concomitantly, in cognitive impairment, including advanced dementia, changes in central nervous system along with changes in the peripheral nervous system due to aging have a significant impact in pain perception. Often clinicians decide to prescribe opioids in order to relief pain, also without a clear indication. Aim: This review aims to investigate the effect of opioids in elderly patients with cognitive impairment. Methods: A literature search of PubMed/Medline, Scopus, and Cochrane databases was conducted using keyword searches to generate lists of articles which were screened for relevance by title and abstract to give a final list of articles for full-text review. Further articles were identified by snowballing from the reference lists of the full-text articles. Results: This review discuss the complex physiological and pharmacological changes in elderly as well as the neurological changes that affect pain perception in this population. Additionally, it focuses on cognitive impairment and pain in Alzheimer’s disease and other dementias, the pain assessment in the elderly with cognitive impairment as well as the safety of opioid use in elderly. Information regarding opioid prescription in nursing homes as well as recorded indications for opioids use, type and dosing of opioid and compliance of treatment in advanced dementia are also provided. Conclusions: Opioid prescription in elderly population with cognitive impairment is particularly complex. All healthcare professionals involved in the care of such patients, need to be aware of the challenges and strive to ensure analgesic use is guided by appropriate and accurate pain assessment.

Mild Cognitive Impairment (MCI) is a clinical syndrome characterized by a moderate decline in one or more cognitive functions with a preserved autonomy in daily life activities [1]. MCI exhibits cognitive, behavioral, psychological symptoms [2]. The executive functions (EFs) are a set of key functions for everyday life and physical and mental health; and allow adapting the behavior to external changes [3-5]. Higher-level executive functions develop from basic EFs (inhibition, working memory, attentional control, and cognitive flexibility). They are planning, reasoning, problem- solving, and fluid intelligence (Gf) [3]. This systematic review investigates the relationship between higher-level executive functions and healthy and pathological aging, assuming the role of executive functions deficits as a predictor of cognitive decline. The systematic review was conducted according to the PRISMA Statement [6-7]. A total of 73 studies were identified. The results indicate that 65.8% of the studies confirm significant EFs alterations in MCI (100% problem solving, 71.4% fluid intelligence, 56.8% planning, 50% reasoning). These results seem to highlight a strong prevalence of higher-level executive functions deficits in MCI elderly than in healthy elderly.

Background: Oncology patients experience a large number of symptoms and, those referring to cognitive performance has an ever-increasing importance in clinical practice due to the increase in survival rates and interest in the patient's quality of life. The studies reviewed show that chemotherapy-related cognitive impairment may occur in 15 and 50% of oncology patients. The main objective of this research was to study the impact of chemotherapy on the cognitive function of patients with locoregional breast cancer.Method: Analytical, prospective, longitudinal study using three measures, unifactorial intrasubject design, non-probability and random selection sampling. The sample comprised women newly diagnosed with locoregional breast cancer in stages I, II, IIIA who received chemotherapy at the University Hospital of Salamanca (Complejo Asistencial Universitario de Salamanca) randomly selected for three years. Semi-structured interviews were conducted, and anxiety and depression (Hospital Anxiety and Depression scale, HAD); quality of life (QLQ-BR23 scale) and the following cognitive variables were assessed: processing speed, attention, memory and executive functions (subtests of the Wechsler Intelligence Scale and the Trail Making Test). Results: The final sample size included 151 participants; 23 were excluded. A decline in cognitive performance was observed in patients which was not completely recovered two months after chemotherapy had been completed. Also, worse cognitive performance was observed in patients with anxious or depressive symptoms. There is a negative impact on the quality of life. Conclusion: Chemotherapy has an impact on the cognitive performance of oncology patients in most of the cognitive domains studied.

In our country, the aging society is rapidly progressing, with an increase in patients with chronic kidney disease (CKD) and those undergoing dialysis, coupled with the aging of the population. As a result, the number of individuals with cognitive impairment (CI) is rising, and addressing this issue has become an urgent problem. One characteristic of dementia in CKD patients is the high frequency of vascular dementia, making the prevention through the management of classical risk factors such as hypertension, diabetes mellitus, dyslipidemia, smoking, etc., associated with atherosclerosis and arteriosclerosis. Other effective measures, including the use of renin-angiotensin system inhibitors, addressing anemia, exercise therapy, and lifestyle improvements, have been reported. Incidence and progression of CI may also be influenced by the type of dialysis or kidney replacement therapy, with reports suggesting that long-duration dialysis, low-temperature hemodialysis, peritoneal dialysis, and kidney transplantation (KTx) can have a possible preferable effect on preserving cognitive function.

Abstract: Background: Adolescents frequently self-report pain, according to epidemiological research. The knee is one of the sites where the pain is most common. One of the main factors contributing to the number of years people spend disabled and having substantial personal, societal, and economic burdens globally is musculoskeletal disorders. Insidious, slowly building onset that neither the adolescent nor the parent is aware of [5]. Patellofemoral Pain (PFP) is a clinical knee pain commonly affecting adolescents. In the present study, the authors aimed to estimate the frequency of knee pain in Saudi adolescents. Methods: This cross-sectional survey carried out from June to November 2022 included 676 adolescents, ages 10 to 18. The data are presented as frequencies and percentages for categorical variables. Analysis of variance (ANOVA) was used to compare means between groups, while the chi-square test was used for the comparison of categorical variables. Statistical significance was set at p < 0.05. Results: Adolescents were invited to take part in the study; 57.5% were female and 42.5% were male, and 68.8% were aged between 15 and 18. The prevalence of knee pain was considerably high among females (26%), while it was 19.2% among males. Moreover, age was a significant predictor for knee pain, and BMI was as well. We also found a significant difference between BMI classification and stiffness of the knee (p = 0.008). There is a difference between adolescents who do physical activities in leisure and difficulty bending (p = 0.03). Conclusion: Our study noted a high rate of knee pain among adolescents, so we need to raise awareness about risk factors. Adolescent knee pain can be prevented with conservative methods and some minor lifestyle/activity modifications.

Persistence of symptoms beyond three months after COVID-19 infection, often referred to as post-COVID-19 condition (PCC), is commonly experienced. It is hypothesized that PCC results from autonomic dysfunction with decreased vagal nerve activity, which can be indexed by low heart rate variability (HRV). The aim of this study was to assess the association of HRV upon admission with pulmonary function impairment and number of reported symptoms beyond three months after initial hospitalization for COVID-19 between February and December 2020. Follow-up took place three to five months after discharge and included pulmonary function tests and the assessment of persistent symptoms. HRV analysis was performed on one 10s electrocardiogram obtained upon admission. Analyses were performed using multivariable and multinomial logistic regression models. Among 171 patients who received follow-up, and with an electrocardiogram at admission, decreased diffusion capacity of the lung for carbon monoxide (DLCO) (41%) was most frequently found. After a median of 119 days (IQR 101-141), 81% of the participants reported at least one symptom. HRV was not associated with pulmonary function impairment or persistent symptoms three to five months after hospitalization for COVID-19.

Therapeutic hypothermia (TH) has emerged as a promising approach with neuroprotective effects that can mitigate secondary brain damage and intracranial pressure in the acute phase after successful mechanical thrombectomy. However, the effect of TH on cognitive impairment has yet fully elucidated. In the present study, we demonstrated whether TH can improve cognitive impairment in a transient middle cerebral artery occlusion (tMCAO) mouse model Nine-week-old C57BL/6N mice (male) were randomized to three groups: sham, tMCAO, and tMCAO with TH. One month after model induction, cognitive function test and regional cerebral glucose metabolism were evaluated using the Y-maze test and positron emission tomography with fluorine-18 fluorodeoxyglucose, respectively. tMCAO led to cognitive impairment, which was improved by TH. The cerebral glucose metabolism of the thalamus was significantly recovered in the TH group compared to that in the tMCAO group. These results suggest that TH might have potential as a therapeutic strategy for improving the ischemia/reperfusion-induced cognitive impairment.

miRNA regulatory axes in blood of MCI patients, which includes lncRNA-SNHG16, lncRNA-H19 and lncRNA-NEAT1. Microarray investigations have demonstrated modifications in the expression of long non-coding RNAs (lncRNA) in blood of patients with MCI compared with control samples. This is the first study to explore lncRNA profiles in Mild Cognitive Impairment blood. Our study proposes RNAs targets involved in molecular pathways connected to the pathogenesis of MCI.

Mild cognitive impairment (MCI) is when brain function declines. It is a transition stage between normal aging and Alzheimer's disease (AD) and may be an underlying symptom of AD. Improper use of test instruments or imperfect test methods in clinical practice often leads to variations in test results. In addition, there may be resistance from the subject if he/she has to undergo multiple screening tests simultaneously. Therefore, the objective of this study was to use virtual reality to create an image testing scenario that integrates Mini-Cog, Short Portable Mental Status Questionnaire (SPMSQ), Mini-mental Status Examination (MMSE), Saint Louis University Mental Status Examination (SLUMS), Clinical Dementia Rating (CDR), and Cognitive Abilities Screening Instrument (CASI), and combine fuzzy logic control (FLC) technology to develop an MCI forecasting system. There were 24 middle-aged to older adults aged 50 to 65 years who participated in the evaluation experiment. The results showed that the MCI forecasting system developed in this study is highly correlated with the traditional screening tests, including Mini-Cog, SPMSQ, MMSE, SLUMS, and CASI. The forecasting system can provide an integrated reference score for testers in making judgments. In addition, the distribution of the System Usability Scale (SUS) evaluation scores for the MCI forecasting system revealed that 87.5% were grade C (good to use) or above, and 29.2% were grade B (extremely good to use) or above. The forecasting system receives positive feedback from the subjects.

Aim. In the current study, we aimed at identifying resting-state brain networks, which are different in patients with depression compared to healthy individuals. Moreover, we analyzed the potential for clinical use of different network measures that could discriminate the two groups and thus help the diagnostic process. Method and subjects. We recruited 90 subjects: 49 healthy controls (HC) and 41 patients with a major depressive episode (MDE). All subjects underwent clinical evaluation and functional resting-state MRI. The data were processed to investigate functional connectivity network measures across the two groups using Brain Connectivity Toolbox. The statistical inferences were made at the functional networks level, using false discovery rate method. Independent samples t-test was performed on the network measures mean values to reveal differences between HC and MDE groups. Permutation-based statistical testing was used to test the significance of the difference between the distributions of the network measures by nodes for HC and MDE groups. Linear discriminant analysis was used to differentiate between the groups. Results and discussion. Significant differences in FC between depressed patients and healthy controls were found with the most prominent changes encompassing within-region as well as between-region connectivity of occipital lobe areas such as precuneus (PreCu), cuneus (Cu), superior occipital gyrus (SOG), lingual gyrus (LG), fusiform gyrus (FG), cerebellum, along with limbic structures including the hippocampus (Hipp) and cingulate gyrus. Linear discriminant analysis demonstrated that the full connectivity matrices, as well as those with only the significant connections identified in advance, were the most precise in differentiating between depression and health. These measures reached precision levels of 97% and 94%, respectively. Conclusion. Our study delivered further evidence about impairment of functional connectivity networks in MDE that may contribute to differentiate patients with depression from healthy subjects.

Zebrafish is an excellent model for observing human genetic disorders. Hearing impairment is the most common genetic disorder including syndromic & non-syndromic hearing loss. Stem cell therapies are considered a new hope in case of hearing impairment. Stem cells are the master cells of the human body and having the capability to differentiate into any other form of cells in more than 200 types of cells (regeneration). This review article describes zebrafish as a biomedical model for stem cell research in hearing impairment, which revolutionized the biomedical arena to compete for the challenges.

There is a lack of research based on in-depth theoretical and scientific knowledge to understand the visually impaired, and there has been little effort in the application of strategies for early intervention to minimize risk these people might encounter during development.. This study used semi-structured interviews from eight persons with visual impairments who had various experiences with resiliency. Three resilience processes based on life experiences were identified: 1) Experience and Adaptation: “self-awareness of disability” and “adaptation disability and the environment”; 2) Facing the Circumstances: “the exposure to concealment and abuse,” “the suppression of potential,” “denial and abandonment by family,” “poverty and disability,” “exchange and self-regulation,” and “social integration” themes; and 3) the Positive Reinforcement: “self-disclosure and jump-starting life,” “maintenance of a positive thinking,” and “socioeconomic independence.” These findings expand the understanding of the factors common to the resilience process experienced by individuals with visual impairment and highlight the importance of psychological support, family, education, and social support.

The prevalence of congenital hearing impairment (HI) is highest in Africa. Estimates evaluated genetic causes to account for 31% of HI cases in Africa, but the identification of associated causative genes mutations have been challenging. In this study, we reviewed the potential roles, in humans, of 38 novel genes identified in a murine study. We gathered information from various genomic annotation databases and performed functional enrichment analysis using online resources i.e. genemania and g.proflier. Results revealed that 27/38 genes are express mostly in the brain, suggesting additional cognitive roles. Indeed, HERC1- R3250X had been associated with intellectual disability in a Moroccan family. A homozygous 216-bp deletion in KLC2 was found in two siblings of Egyptian descent with spastic paraplegia. Up to 27/38 murine genes have link to at least a disease, and the commonest mode of inheritance is autosomal recessive (n=8). Network analysis indicates that 20 other genes have intermediate and biological links to the novel genes, suggesting their possible roles in HI. This study will contribute to advance our knowledge in unravelling the biological roles of novel murine HI genes in humans and could enhance the understanding of the genetic causes of HI in Africans.

Human exposure to carbon nanotubes (CNTs) can cause health issues due to their chemical–physical features and biological interactions. These nanostructures cause oxidative stress, also due to endogenous ROS production, which increases following mitochondrial impairment. The aim of this in vitro study was to assess the health effects, due to mitochondrial dysfunction, caused by a sub-chronic exposure to a non-acutely toxic dose of multi walled CNTs (raw and functionalised). The A549 cells were exposed to MWCNTs (2 µg mL^-1) for 36 days. Periodically, cellular dehydrogenases, pyruvate dehydrogenase kinase 1 (PDK1), cytochrome c release, permeability transition pore (mPTP) opening, transmembrane potential (Δψ m), apoptotic cells, and intracellular ROS were measured. The results, compared to untreated cells and to positive control formed by cells treated with MWCNTs (20 µg mL^-1), highlighted the efficiency of homeostasis to counteract ROS overproduction, but a restitutio ad integrum of mitochondrial functionality was not observed. Despite the tendency to restore, the mitochondrial impairment persisted. Overall, the results underlined the tissue damage that can arise following sub-chronic exposure to MWCNTs.

Background Some patients with mild cognitive impairment (MCI) experience gait disturbances. However, there are few reports on the relationship between gait disturbance and cognitive function in patients with MCI. Therefore, we investigated the neural correlates of gait characteristics related to cognitive dysfunction. Methods Eighty patients diagnosed with MCI from three dementia centres in Gangwon-do, Korea were recruited for this study. We defined MCI as a Clinical Dementia Rating global score of 0.5 or higher, with a memory domain score of 0.5 or greater. The patients were classified as having either early or late MCI based on their Mini Mental Status Examination z-scores. Multiple logistic regression analysis was performed to examine the association between the gait characteristics and cognitive impairment. Analyses included variables such as age, sex, years of education, number of comorbidities, body mass index and height. Results Gait velocity, step count, step length, heel-to-heel base support, swing and stance phase duration, and support time were associated with cognitive function. A decrease in gray matter volume in the right pericalcarine area was associated with gait characteristics related to cognitive dysfunction. An increase in the curvature of gray matter in the right entorhinal, right lateral orbitofrontal, right cuneus, and right and left pars opercularis areas was also associated with gait characteristics related to cognitive dysfunction. Conclusion Since gait impairment is an important factor in determining activities of daily living in patients with mild cognitive impairment, the evaluation of gait and cognitive functions in patients with mild cognitive impairment is important.

Central nervous system (CNS) uses vision, vestibular, and somatosensory information to maintain body stability. Research has shown that there is more lumbar proprioception error among low back pain (LBP) individuals as compared to healthy people. In this study, two groups of 20 healthy people and 20 non-specific low back pain participants (LBP) took part in this investigation. This investigation focused on somatosensory sensors and in order to alter proprioception, a vibrator (frequency of 70Hz, amplitude of 0.5 mm) was placed on the soleus muscle area of each leg and two vibrators were placed bilaterally across the lower back muscles. Individuals, whose vision was occluded, were placed on two surfaces (foam and rigid) on force plate, and trunk angles were recorded simultaneously. Tests were performed in 8 separate trials; the independent variables were vibration (4 levels) and surface (2 levels) for within subjects and 2 groups (healthy and LBP) for between subjects (4×2×2). MANOVA and multi-factor ANOVA tests were done. Linear parameters for center of pressure (COP) (deviation of amplitude, deviation of velocity, phase plane portrait (PPP), and overall mean velocity) and nonlinear parameters for COP and trunk angle ((recurrence quantification analysis) RQA and Lyapunov exponents) were chosen as dependent variables. Results indicated that NSLBP individuals relied more on ankle proprioception for postural stability. Similarly, RQA parameters for the COP on both sides and for the trunk sagittal angle indicated more repeated patterns of movement among the LBP cohort. Analysis of short and long Lyapunov exponents showed that people with LBP caused no use of all joints in their bodies (non-flexible), are less stable than healthy subjects.

Outdoor air pollution is a leading cause of death and premature death globally. Motorcycle-taxi drivers were most at risk associated with occupational exposure to ambient air pollution in urban areas. Therefore, a cross-sectional study was conducted to determine the influencing factors and prediction of lung function impairment in 308 motorcycle-taxi drivers living in Bangkok and adjacent provinces between February and June 2022. The study design included: data collection using questionnaires applied from the Thai version of ATS-DLD-78A: American Thoracic Society Division of Lung Diseases and Department of Disease Control, Ministry of Public Health, Thailand; a collection of respirable dust, and ambient air pollution parameters measured by per-sonal air sampling pump and real-time air quality index (AQI) station, and lung function determined by the spirometer. The results showed that 14 factors were significantly associated with lung function impairment (p<0.05). Apparently, seven influencing factors showing the most association were included: gender, the height of the subjects, history of allergies, exposure to respirable dust, mask types, helmet types, and family history of lung disease. The lung function impairment of motorcycle-taxi drivers was significantly predicted in 28.1% by regression analysis of these seven variables (R2=0.281). Therefore, this is the first report on influencing factors and prediction of lung function impairment among motorcycle-taxi drivers. These findings would be very useful for preventing and controlling measure ambient air pollution, setting policies and strategies to mitigate the risks for motorcycle-taxi drivers and the other ex-posed population.

Cognitive impairment is a core feature of schizophrenia, playing a pivotal role in understanding the causes, processes, and outcomes of the disorder. Cognitive impairments in schizophrenia encompass a wide range of domains, including processing speed, episodic memory, working memory, and executive function. These deficits persist throughout the course of the illness and significantly impact functional outcome and quality of life. Therefore, identifying the biological basis of cognitive deficits in schizophrenia and developing effective treatments are imperative. The role of N-methyl-D-aspartate (NMDA) receptors in synaptic transmission and plasticity has long been recognized, making them potential targets for schizophrenia treatment. This review will focus on emerging pharmacology targeting NMDA receptor, offering strategies for the prevention and treatment of cognitive deficits in schizophrenia.

Attention Deficit-Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with high incidence in children and adolescents characterized by motor hyperactivity, impulsivity, and inattention. MRI-based evidences support that neuroanatomical abnormalities as the volume reduction of neocortex and hippocampus are shared by several neuropsychiatric diseases as schizophrenia, autism spectrum disorder and ADHD. In addition, it is well documented the abnormal development and postnatal pruning of dendritic spines of neocortical neurons in schizophrenia, autism spectrum disorder and intellectual disability. A recent report using the prenatal nicotine exposure murine model of ADHD support a delay in spine maturation in CA1 neurons correlated with impaired working memory and hippocampal long-term potentiation (LTP). In vivo spine imaging show that dendritic spines are dynamic structures exhibiting Hebbian and homeostatic plasticity triggering intracellular cascades involving glutamate receptors, calcium influx and remodeling of F-actin network. The LTP-induced insertion of postsynaptic glutamate receptors is associated to the enlargement of spine head and long-term depression (LTD) to the spine shrinkage. In this review, we summarize recent evidence emerged from meta-analysis of brain imaging data from ADHD patients, risk loci from global genome-wide analysis and new reports focused on spine molecular structure and dynamics using in vivo imaging in neocortex and hippocampus.

(1) Background: Attention Deficit Hyperactivity Disorder (ADHD) and Developmental Language Disorder (DLD) are neurodevelopmental disorders that affect various areas of chil-dren’s development, such as language. There is an emerging idea that ADHD is characterised by the presence of language difficulties, which could be explained by the high comorbidity between ADHD and DLD. The purpose of this study is to analyse the empirical evidence of language com-petence in children aged 6–17 years old, diagnosed with ADHD and/or DLD. (2) Method: Fifteen studies with experimental designs were identified from Scopus, PsycINFO and WoS databases, reporting on language skills in children diagnosed with ADHD and/or DLD. Studies relating ex-ecutive functioning to language skills in this target population were also included. (3) Results: The literature is heterogeneous and different components of language are also examined. Even though the results are contradictory they convincingly demonstrate that there are overlapping symptoms between ADHD and DLD, such as language skills and executive functions. (4) Conclusions: the differences in the samples limit the generalisability of the results. Therefore, this review highlights the importance of considering language skills when designing individualised interventions for the population with ADHD and DLD, both in comorbidity and in isolation.

Cognitive impairment in patients with Parkinson’s disease (PD), which may occur in various severities, represents one of the commonest and most disabling non-motor manifestations during the course of the disease, causing a negative impact on patients’ quality of life. Eventually, it becomes a burden for the family members and/or the caregivers of patients, as it progresses to PD dementia. Current pharmacological treatments for cognitive impairment in PD exhibit partial efficacy, while novel effective therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline, and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, improvement of mitochondrial function, regulation of synaptic plasticity, impact on gut-brain axis, modulation of neuroinflammation, upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this overview, we aim to cover the clinical aspects of PD associated cognitive impairment, highlighting recent evidence on emerging treatment approaches that are currently under investigation at a preclinical and clinical level.

ackground: This study aimed to examine the effects of a woodworking program on psychosocial health in older adults who had mild cognitive impairment (MCI) or mild dementia (MD) in Korea. Setting: The study was carried out in a dementia center in Seoul in Korea. Population: A total of 61 participants who had MCI or MD were allocated into two groups: the experimental group (EG, n = 35) and the control group (CG, n = 26). Methods: This study was carried out using a nonequivalent control group pre-test–post-test design. The EG participated in the woodworking program a total of 10 times for 120 min per session twice a week for 5 weeks, and the CG did not participate in the woodworking program. Both groups completed the same survey before and after the intervention. In the survey, demographic characteristics, psychological health (life satisfaction, depression, self-efficacy, and resilience), and social health (social isolation and social support) were measured. Results: In the within-group comparison, there was no significant difference between any factors of the CG before and after the intervention. In contrast, the EG had a significant improvement before and after the woodworking program. Participants in the EG with MCI and MD significantly improved their social support (p < 0.05). Psychological factors (life satisfaction, depression, and self-efficacy) were positively changed, although not significantly. Conclusions: The woodworking program promoted psychosocial health, such as life satisfaction, resilience, and social support, among older adults with mild cognitive impairment and mild dementia.

A frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed over past decades. Accordingly, much evidence has been reported which indicates that microvascular endothelial dysfunction, due to cerebrovascular risk factors (e.g., atherosclerosis, obesity, diabetes, smoking, hypertension, aging), precedes cognitive decline in Alzheimer's disease and contributes to its pathogenesis. By incorporating appropriate drug(s) into biomimetic (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), and crosses the blood-brain barrier (BBB). Such targeting allows for various Alzheimer's-related cell types to be simultaneously searched out, in vivo, for localized drug treatment. This in vivo targeting advantage may be particularly important for repurposing an FDA-approved drug, especially one which has shown the added ability to restore some cognitive functions in certain animal models of Alzheimer's disease (e.g., the anticancer drug bexarotene); this (candidate repurposing) drug up to now, by itself (i.e, without nanocarrier), displayed poor CNS penetration in human subjects.

Network neuroscience delves into comprehending the intricate arrangement and interactions within the neural networks of the brain. By merging insights from both neuroscience and network theory, it investigates the brain's structure and function through the lens of interconnected nodes (symbolizing brain regions) and edges (symbolizing the connections among these regions) forming a dynamic network. Graph metrics play a pivotal role in neuroscience by providing quantifiable insights into the intricate connectivity patterns within the brain's neural networks. Frequently, nodes are extracted from functional or structural atlases, which can lead to diverse shapes and sizes. Nevertheless, our understanding of how these differing node characteristics and definitions impact the computed graph metrics in neuroimaging data remains limited. This study adopts a data-driven methodology to delineate functional nodes, subsequently examining the influence of their sizes on resultant graph metrics. By employing the Neuromark framework, an entirely automated independent component analysis (ICA) is applied to resting state fMRI data. Through this, functional network connectivity (FNC) matrices are computed—capturing Pearson correlations between component-time courses—while employing a proportional threshold to streamline node connections based on these correlations. Subsequently, various global and local graph metrics are computed, offering insights into network characteristics. Global metrics provide an overarching summary of the network structure, while local measures delve into structural intricacies at the individual component level. Node sizes are computed based on voxel counts surpassing a designated threshold. Next, we calculated the Pearson correlation between the obtained node sizes and the graph metrics, which we term 'node-metric coupling' (NMC). Our findings revealed consistent and noteworthy correlations between the values of graph metrics and the dimensions of brain nodes. To delve deeper into the implications of this correlation, we examined the node-metric coupling within a dataset comprising Alzheimer's disease, mild cognitive impairment, and control subjects. The disparities observed in node-metric coupling among these groups underscore the necessity of accounting for this factor during analysis. The two principal outcomes of this study are as follows: Firstly, the substantial interplay between varying node sizes within a given atlas and the resultant graph metrics; and secondly, the potential utility of node-metric coupling as a viable biomarker for brain disorders. These discoveries hold significant ramifications. While comparing studies employing diverse atlases is already a challenge, our work highlights an additional, critical source of variability: accounting for node sizes. Consequently, the association between intra-atlas node size and graph metric should be thoughtfully acknowledged in future neuroimaging investigations.

Mild cognitive impairment (MCI) and mild dementia are a clinically relevant health problem in the elderly and Alzheimer's disease being the most common neurodegenerative disorder. Furthermore, MCI and mild dementia are characterized by a deterioration of cognitive function and their diagnosis is mainly based on cognitive examination and, the prognosis of the disease seems to be an essential reason for the diagnosis, because there is a high risk of cognitive decline in the two syndromes. This review describes the effectiveness of Ginkgo biloba (EGb761®) leaf extract for the treatment of dementia syndrome and EGb761® combination therapy with other medications for symptomatic dementia. Tebonin® is a drug of plant origin based on the active ingredient “Ginkgo biloba”. This drug has shown encouraging results, improving cognitive function, neuropsychiatric disorders and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild dementia. Nowadays, there is little evidence to support the efficacy of EGb761® combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb761® in mixed therapy.

Although the most common forms of brain injury in preterm infants have been associated with adverse neurodevelopmental outcomes, existing MRI scoring systems lack specificity, do not incorporate clinical factors, and are technically challenging to perform. The objective of this study was to develop a web-based, clinically-focused prediction system which differentiates severe from normal-moderate neurodevelopmental outcomes at two years. Infants were retrospectively identified as those who were born ≤30 weeks gestation, had MR imaging at term-equivalent age, and neurodevelopmental testing at 18-24 months. Each MRI was scored on injury in three domains (intraventricular hemorrhage, white matter injury, and cerebellar hemorrhage) and clinical factors strongly predictive of outcome were investigated. A binary logistic regression model was then generated from the composite of clinical and imaging components. A total of 154 infants were included (mean GA = 26.1±1.8 weeks, BW = 889.1±226.2 grams). The final model (imaging score + ventilator days + delivery mode + antenatal steroids + ROP requiring surgery) had strong discriminatory power for severe disability (AUC=0.850), with a PPV of 76% and NPV of 90%. Available as a web-based tool, it can be useful for prognostication and targeting early intervention services to infants who may benefit most from such services.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative condition caused by repeated traumatic brain injuries (TBIs) leading to cognitive, behavioral, and motor dysfunctions. This study examined the relationship between cognitive impairment and clinical syndromes among 145 CTE patients aged 18 to 75 years who underwent inpatient treatment at the Ternopil Regional Clinical Psychoneurological Hospital between 2021 and 2022. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), with results classified into four categories: normal, mild impairment, moderate impairment, and dementia. Statistical analysis revealed significant associations between cognitive impairment and specific neuroimaging changes, including ventricular dilatation. Clinical syndromes, such as cognitive disorder syndrome, also showed significant associations with cognitive impairment (p &lt; 0.001). Using logistic regression, we developed a predictive model to estimate the probability of cognitive impairment based on various clinical features, including memory loss, attention deficits, and sleep disturbances. The model demonstrated high accuracy, with a receiver operating characteristic (ROC) curve showing a sensitivity of 91.0% and a specificity of 92.5%, yielding an area under the curve (AUC) of 0.964 (95% CI: 0.934 - 0.994). These findings suggest that specific neuroimaging and clinical features can predict cognitive impairment in CTE patients.

The Global Burden of Disease Study (GBD 2019 Diseases and Injuries Collaborators) found that diabetes significantly increases the overall burden of disease, leading to a 24.4% increase in disability-adjusted life years. Persistently high glucose levels in diabetes can cause structural and functional changes in proteins throughout the body, and the accumulation of protein aggregates in the brain is associated with the progression of Alzheimer's Disease (AD).To address this burden of type 2 diabetes mellitus (T2DM), a combined aerobic and resistance exercise program was developed based on the recommendations of the American College of Sports Medicine. The prospectively registered clinical trials (https://www.clinicaltrials.gov/ct2/show/NCT04626453, https://www.clinicaltrials.gov/ct2/show/NCT04812288) involved two groups: an Intervention group of older sedentary adults with T2DM and a Control group of healthy older adults who could be either active or sedentary. The completion rate for the 2-month exercise program was high, with participants completing on an average of 89.14% of the exercise sessions. This indicated that the program was practical, feasible, and well-tolerated, even during the COVID pandemic. It was also safe, requiring minimal equipment and no supervision. The exercise instructions were easy to understand, making them suitable for older adults with cognitive decline.The near-infrared spectroscopy (NIRS) based brain and muscle oxygenation study provided evidence on brain overactivation among older adults with T2DM, supporting the compensatory theory. It also demonstrated that the 2-month combined exercise intervention effectively reduced brain overactivation and contributed to improved cognitive function. Operational modal analysis showed an exercise-related effect on the very low-frequency hemodynamic oscillations cluster, which may be associated with better vascular muscle and/or perivascular neurogenic regulation. Furthermore, we personalized the exercise duration and interval based on muscle oxygenation during physical tasks, leading to improvements in muscle oxidative capacity within just two months. This finding has practical implications for physical therapists, as they can target muscle oxygenation changes during physical tests to prescribe appropriate exercise doses for enhancing physical performance.

This study focuses on mimicking constitutive phosphorylation in the N-terminus of the myosin regulatory light chain (S15D-RLC) as a rescue strategy for the mutation-induced cardiac dysfunction in transgenic (Tg) models of restrictive (RCM) and dilated (DCM) cardiomyopathy caused by mutations in myosin essential (ELC) or regulatory (RLC) light chains. S15D-RLC phosphomimetic was reconstituted in left ventricular papillary muscle (LVPM) fibers from two mouse models of cardiomyopathy, RCM-E143K ELC and DCM-D94A RLC, along with their corresponding Tg-ELC and Tg-RLC wild type (WT) mice. The beneficial effects of S15D-RLC in rescuing cardiac function were manifested by S15D-RLC-induced destabilization of the super-relaxed (SRX) state that was observed in both models of cardiomyopathy. S15D-RLC promoted a shift from the SRX state to the disordered relaxed (DRX) state, increasing the number of heads readily available to interact with actin and produce force. Additionally, S15D-RLC reconstituted fibers demonstrated significantly higher maximal isometric force per cross-section of muscle compared with reconstitution with WT-RLC protein. The effects of the phosphomimetic S15D-RLC were compared to those observed for Omecamtiv Mecarbil (OM), a myosin activator shown to bind to the catalytic site of cardiac myosin and increase myocardial contractility. A similar SRX↔DRX equilibrium shift was observed in OM=treated fibers as in S15D-RLC-reconstituted preparations. Additionally, treatment with OM resulted in significantly higher maximal pCa 4 force per cross-section of muscle fibers in both cardiomyopathy models. Our results suggest that both treatments with S15D-RLC and OM may improve the function of myosin motors and cardiac muscle contraction in RCM-ELC and DCM-RLC mice.

People with specific TREM2 gene variants are more prone to develop Alzheimer's disease (AD). The TREM2 receptor regulates the number of myeloid cells, phagocytosis, and the inflammatory response via interacting with apolipoproteins and amyloid. Higher TREM2 expression has been found to protect against AD. When TREM2 activity increases, the activity of genes involved in the activation of microglia cells decreases. This can improve the efficiency of phagocytosis. When TREM2 is highly expressed and the inflammasome is activated, the results are not always congruent. Therefore, this study aimed to discover how sTREM2 levels in CSF and plasma samples relate to other indices of AD pathology. We examined 98 AD plasma samples, 35 plasma samples of subjects with mild cognitive impairment (MCI), 11 healthy controls (HC) plasma samples, as well as 155 AD CSF samples, 90 MCI CSF samples, and 50 HC CSF samples. CSF sTREM2 levels were higher in the AD group than in the MCI and HC groups, in contrast to plasma sTREM2. This shows that CSF sTREM2 levels could be used to distinguish between healthy and AD patients. CSF sTREM2 levels were significantly correlated with neurofibrillary changes, cognitive decline, and inflammasome activity in AD patients. While our findings are consistent with previous research, future studies will need to include more patients and employ standardized methodological approaches to add CSF sTREM2 to the list of biomarkers for AD.

Background: Cognitive-behavioral alterations can occur after an acquired brain injury. It is a stressful situa-tion for patient and relatives. Objectives: To develop and evaluate a synchronous online training program on emotional intelligence (EI) for caregivers of adult patients with cognitive-behavioral impairment due to acquired brain injury. Methods: A quasi-experimental study was designed, a target population of ten caregivers attended to a one-month virtual synchronous course about EI. The emotional status of caregivers was registered one-month-previous and one-month-post program using comparative measures: The Trait Meta-Mood Scale (TMMS-24) and the Positive and Negative Affect Schedule (PANAS). Results: Median age of the ten caregivers was 48 years, 80% of women with a median care-time of 6 years. 50% of them were spouses of the patients. 60% of the patients were affected by stroke (hemorrhagic or ischemic cause). The main cognitive impairment of the patients reported by relatives was memory deficit. After re-ceiving training, favorable changes were found regarding emotional affect measured with the PANAS, both positive (increase) and negative (decrease), as well as with the TMMS-24-mood-repair area (p < 0.05). Conclusions: Training in EI helps caregivers to make their mood more positive and improve aspects of their emotional intelligence such as emotional regulation.

The purpose of this study was to investigate the effect of circuit training on β-amyloid, BDNF, and cognitive function in untrained obese elderly Korean women. The subjects for the study were aged 65–70 years, composed of the circuit training group(n=12) and control group(n=11). The 60-minute combined exercise was performed 3 times per week for 16 weeks. Exercise intensity was progressively increased from 40% HRR to 70% HRR. The test data were analyzed by paired t-test, independent t-test, and two-way repeated measures ANOVA, and the alpha level of .05 was set for all tests of significance. The findings of this study were as follows: β-amyloid significantly decreased after the exercise group had compared to before the exercise and BDNF and cognitive function significantly increased after the exercise group had compared to before the exercise. However, there were no significant changes in β-amyloid, BDNF, and cognitive function in the control group Therefore, it is suggested that the circuit training used in this study could be an effective exercise method for improving the risk factors of cognitive impairment in obese elderly Korean women.

Constant exposure to a variety of environmental factors has become increasingly problematic. A variety of illnesses are initiated or aided by the presence of certain perturbing factors. In the case of autism spectrum disorder, the environmental component begins to play an important part in de-termining the overall picture. Moreover, the lack of therapies to relieve existing symptoms com-plicates the fight against this condition. As a result, the use of animal models has made biomedical research easier and more suited for disease investigations. The current study used zebrafish as an animal model to mimic a real-life scenario: acute exposure to an increased dose of pesticides, fol-lowed by prospective intervention-based therapy with vitamin B12 (vit. B12). It is known that vit. B12 is involved in brain function, nerve tissue and red blood cell formation. Aside from this, the role of vit. B12 in the redox processes was recognized for its help against free radicals. To investigate the vit. B12 effect, fish were divided in four different groups and exposed to a pesticide mixture (600 μg L-1 fipronil + 600 μg L-1 pyriproxyfen) and 0.24 μg L-1 vit. B12 for 14 days. The impact of the compound was assessed daily by EthoVision software for behavioral observations, especially for sociability, quantified by the social interaction test. In addition, at the end of the study, the activities of su-peroxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were measured. Results showed significant improvements for locomotor activity parameters and a pos-itive influence of vitamin on sociability. Regarding the state of oxidative stress, a high activity was found for SOD and GPx in the case of vit. B12, while the mixture of pesticides and vitamin had a lower level of MDA. In conclusion, the study brings new data about the effect of vit. B12 in zebrafish, highlighting the potential use of vitamin supplementation to maintain and help the organism function.

Inflammatory activation within the brain was linked to a decrease in cognitive abilities, however the molecular mechanisms implicated in the development of inflammatory-related cognitive dysfunction and its prevention are poorly understood. This study compared responses of hippocampal transcriptomes 3 months after the striatal infusion of lipopolysaccharide, alone (LPS; 30 µg) resulting in memory loss, or with dexamethasone (DEX; 5 mg/kg intraperitoneal) pretreatment, which abolished the long-term LPS-induced memory impairment. After LPS alone, a significant elevation in the expression of immunity/inflammatory-linked genes, including chemokine (Cxcl13), cytokines (Il1b, Tnfsf13b), and major histocompatibility complex (MHC) class II members (Cd74, RT1-Ba, RT1-Bb, RT1-Da, RT1-Db1) was revealed. DEX pretreatment did not change expression of these genes, but significantly affected expression of genes encoding ion channels, primarily calcium and potassium channels, regulators of glutamate (Slc1a2, Grm5, Grin2a) and GABA (Gabrr2, Gabrb2) neurotransmission which enriched in such GO biological processes as “Regulation of transmembrane transport”, “Cognition”, “Learning”, “Neurogenesis”, and “Nervous system development”. Taken together, the data suggest that: (1) pretreatment with DEX did not markedly affect LPS-induced prolonged inflammatory response; (2) DEX pretreatment can affect processes associated with glutamatergic signaling and nervous system development, possibly involved by that in the recovery of memory impairment induced by LPS

This paper addresses the grammatical challenges associated with the development of clause complexity, focusing on the performance of a group of monolingual Spanish-speaking schoolchildren with Specific Language Impairment/Developmental Language Disorder (SLI/DLD) in a longitudinal corpus of oral narrative samples. The study examines the presence of interclause relations of subordination and equivalence (hypotaxis and parataxis) in language samples of two groups: an experimental group made up of 24 schoolchildren with SLI/DLD and a control group made up of 24 schoolchildren with typical development (TD). The results show that while both groups use parataxis as the most common relation between clauses in all school grades, there is a significant decrease in paratactic relations and a significant increase in hypotactic relations from first to fourth grade of primary education. Although the development patterns are highly similar, the SLI/DLD group shows greater difficulties in mastering more complex (hypotactic) relations in fourth grade compared to the control group, indicating that they are less sophisticated in the use of these types of complex relations. These findings suggest that focused support on the most complex structures is needed towards the fourth grade of primary education, given the demands of the school academic register from 6 and 7 years of age, and the potential problems that the development of clause complexity can cause in school-age children.

Introduction:Few robust studies have analyzed association between cognitive tests and the marital status of Mild Cognitive Impairment (MCI) group with ADNI dataset. To test the hypothesis that Rey Auditory Verbal Learning test (RAVLT) cognition performance with marital status is associated with greater odds of MCI group than either RAVLT independently, we used TADPOLE data to evaluate cross-sectional associations between RAVLT performance in immediate response, learning, forgetting, and perception of forgetting with marital status and MCI. Methods: Subjects with MCI and Normal Cognition were included. Logistic regression models indicate associations between four RAVLT subgroups (low and high performance of immediate response, immediate response with learning, performance of immediate response with learning and forgetting, performance of immediate response with learning, forgetting and perception of forgetting) and MCI group. Models adjust for age, sex, race, marital status, ethnicity, education, APOE4 genotype, hippocampus, whole-brain, ventricles and ICV. Results: The sample (n=6560) had a mean age of 77 / 67 years, 44% were female, 58% in MCI group. Only all RAVLT subgroups test with age 61 to 70(OR 0.26, 95% CI 0.15-0.45), age 71 or older(OR 0.07, 95% CI,0.04-0.12), race:black/african american(OR 0.13, 95% CI 0.03-0.52)race:more than one(OR 0.05, 95% CI 0.01-0.24), marital status:never married(OR 0.2, 95% CI 0.12-0.34). Conclusion: Studies are needed to evaluate other cognitive test with missing data within TADPOLE dataset as modifiable risk factor for MCI.

Subjective cognitive decline (SCD) would correspond to a preclinical phase of Alzheimer's disease. The aim of this study was to find associations between lifestyle individual factors compatible scores with cognitive impairment (CI) in SCD people. Methods: This is a case-control study to detect SCD, CI and potential associated factors in 497 patients over 50 years in Community Pharmacies. Three screening tests detected possible CI and patients with at least one test compatible with CI were referred to Primary Care to be evaluated. Results: In self-complaint patients statistically significant with depressive feelings were found (86.8%) with benzodiazepines consumers (83.9%) and female patients (81.2%). Thirty percent of our sample obtained scores compatible with CI. Being older than 70 years old increased the odds of obtaining scores compatible with CI. High level education, reading and internet use were able to reduce the odds of positive scores compatible with CI (37%-91%, 7%-18% and 67%-86%), whereas, one extra hour television/day increased the risk in 8%-30%. Reading was able to nullify the effect of both internet and TV consumption. Conclusion: Not just the age but also modifiable lifestyle factors are acting in favour of a cognitive decline.

Amnestic mild cognitive impairment (aMCI) is a condition characterized by mild deficits in episodic and semantic memory and learning. The conversion rate of aMCI to Alzheimer disease (AD) is significantly higher in aMCI than in the general population. The aim of this study is to examine whether aMCI is a valid diagnostic category or whether aMCI comprises different subgroups based on cognitive functions. We recruited 60 aMCI patients, 60 with AD and 61 healthy controls who completed neuropsychological tests of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-NP) and biomarkers including serum anion gap (AGAP). Principal component analysis, support vector machine and Soft Independent Modeling of Class Analogy (SIMCA) showed that AD patients and controls were highly significantly discrimanted from each other, while patients with aMCI overlap considerably with normal controls. SIMCA showed that 68.3% of the aMCI patients were assigned to the control class (named: aMCI-HC), 15% to AD (aMCI-AD), while 16.6% did not belong to either class (aMCI-strangers). aMCI-HC subjects showed sings of very mild cognitive decline and impaired recall. aMCI-strangers showed signs of mild cognitive impairment with impaired fluency and naming. aMCI-AD cases showed a cognitive profile reminiscent of AD an increased AGAP levels. In conclusion, our SIMCA model may classify subjects afforded a clinical diagnosis of aMCI according to Petersen’s criteria into three clinically relevant subgroups and help in the early detection of AD by identifying aMCI patients at risk to develop AD and those that have an AD prodrome.

Cognitive function, arthrogryposis, obstetrics palsy, children, motor disorder

Cognitive impairment and sarcopenia may share common risk factors and pathophysiological pathways. This study was performed to examine the association between impairments in specific cognitive domains and sarcopenia (and its defining components) in a large group of community-dwelling older adults. Cross-sectional analysis was performed on the baseline data of 3,014 adults aged 70–84 years enrolled in the Korean Frailty and Aging Cohort Study (KFACS). The final analysis included 1,887 adults underwent dual-energy X-ray absorptiometry and cognitive function assessments. Those with disability in activities of daily living, dementia, severe cognitive impairment, Parkinson’s disease, musculoskeletal complaints, neurological disorders, or who were illiterate were excluded. Cognitive function was assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet, the Frontal Assessment Battery. For sarcopenia, we used the diagnostic criteria of the Asian Working Group for Sarcopenia. The prevalence of sarcopenia was 9.6% for men and 7.6% for women. Sarcopenia (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.04–2.99) and slow gait speed (OR 2.58, 95% CI 1.34–4.99) were associated with cognitive impairment in men. Only slow gait speed (OR 1.88, 95% CI 1.05–3.36) was associated with cognitive impairment in women. Sarcopenia is associated with cognitive impairment mainly due to slow gait speed. Our results suggested that cognitive impairment domains, such as processing speed and executive function, are associated with sarcopenia-related slow gait speed.

Multiple sclerosis (MS) is a persistent inflammatory disease affecting the central nervous system. Bruton's tyrosine kinase (BTK) is an enzyme crucial in the communication process of B cells, which have a significant impact on the development of MS. Recently, BTK inhibitors have emerged as a promising treatment strategy for MS due to their ability to modulate the immune system. In this study, an extensive literature search was performed utilizing multiple databases, such as PubMed, Embase, and Scopus to examine the potential use of BTK inhibitors in managing cognitive disorders experienced by individuals with MS. We found that BTK inhibitors targeting microglia offer potential advantages for managing neurodegeneration associated with cognitive impairments in MS patients by slowing down degeneration processes effectively. Their ability to impact microglial function and penetrate the CNS positions them as promising candidates for improving cognitive function. This study suggests that BTK inhibitors provide new possibilities for managing inflammatory and neurodegenerative phases of MS through their effects on microglia activation pathways. Further research and clinical trials are necessary to fully explore their efficacy in treating MS while addressing barriers related to cognitive impairment.

Background: dementia is a significant health issue worldwide. Mild cognitive impairment (MCI) can transform into dementia over time. General practitioners may be the first to notice the cognitive deficit, so they may need a screening test in the event of suspicion, which they must be able to use under great time pressure. We examined the usability of the Hungarian Test Your Memory (TYM-Hun) self-administered dementia test in general practice, and with the results of the received tests, we tried to draw conclusions regarding the population. Methods: In the four Hungarian cities with medical universities, general practitioners filled out 368 questionnaires with their clients over 50 years of age. Results: the total scores of the test showed a significant correlation with education and the type of occupation, while a significant negative correlation with age. We found the clock drawing test and recall indicates cognitive decline the earliest. Based on the TYM-Hun results, the prevalence levels for MCI and dementia are slightly higher in Hungary than globally. Conclusion: the test can sensitively indicate MCI and early-stage dementia as a screening test, and two of its subtests can raise the possibility of cognitive impairment at an earlier age than the others.

Cognitive impairment in older adults is associated with poor gait performance, physical decline, falls and poor quality of life. This paper analyzes the feasibility and efficacy of a tango-based in-tervention in older people with cognitive impairment living in nursing homes. A multicenter study, with pre and post-test, was carried out. Intervention attendance, well-being, physical abilities (Short Physical Performance Battery), walking performance, functional capacities (Katz Index), and quality of life (Quality of Life in Alzheimer’s Disease) were assessed. Fifty-four participants (84.9 ± 6.7 years, Mini Mental State Examination 14.5 ± 7.4) completed the protocol. Intervention attendance was 92%, and the mean subjective well-being after each session was 4.5 ± 0.5 (on a five-point scale). Statistically significant improvement was found in the quality of life (p = 0.030). Non statistically significant changes were found in walking performance, physical abilities, or in functional capacities. The study shows feasibility and suggests evidence for the effects of Tango therapy on well-being and quality of life. Further studies are necessary to contrast these findings and to verify the role of Tango interventions as a holistic approach to prevent functional decline in older people with cognitive impairment.

Background: Differential diagnosis between polymyalgia rheumatica (PMR) and seronegative elderly-onset rheumatoid arthritis (SEORA) is not easy, to the point that in the past they were considered the same entity. In these patients, sleep disorders have been scarcely assessed, and considered as expression of mood disorders such as depression and anxiety. Methods: In 38 Caucasian elderly patients (median age: 73.9 ± 8.06 years) consecutively referred to two outpatient clinics from January to May 2018 with diagnosis of PMR and SEORA, sleep impairment was assessed using the Medical Outcomes Study-Sleep scale (MOS-SS). Depression and anxiety were assessed using the Neuropsychiatric Inventory (NPI) score, with point 0 for absent and point 3 for severe. Comorbidities were assessed using the Cumulative Illness Rating Scale (CIRS). Patients taking medications used to treat sleep disturbance or that could favor sleep disturbances were excluded. The study was approved by the local ethics committee and carried out in accordance with the Helsinki Declaration, revised 2013. Every patient signed an informed consent form at the time of the first visit. Results: MOS-SS total point in PMR patients was significantly higher than in SEORA patients (47.60 ± 8.4 vs 28.26 ± 12.4; P = 0.000). After six-month therapy with prednisone (12.5–15 mg/day, followed after 4 weeks by gradual tapering), MOS-SS total point improved in the two groups of patients, with no significant difference (17.0 ± 6.2 vs 17.8 ± 4.2; P = 0.644). No correlation was found between MOS-SS and comorbidities, and between MOS-SS, anxiety or depression. Conclusions: Our data suggest that the assessment of sleep impairment could be very useful in the differential diagnosis between PMR and SEORA. Up today, the reasons why patients with PMR have—at the time of diagnosis—a sleep impairment higher than SEORA are speculative. Further ad hoc complementary studies in multicenter cohorts are needed.

This study aims to develop an elderly care system for improving the interpersonal relationship of the elderly with mild cognitive impairment (MCI) by employing the speaker recognition technique and association functionality of social network platforms. Firstly, the speaker recognition units based on the Gaussian Mixture Model (GMM) and Gaussian Mixture Model-Universal Background Model (GMM-UBM) are implemented to identify the visitor via individual input utterance. After the visitor is identified, the proposed system will be linked to the private database and social network platforms to extract the associated message of two parties. Experimental results indicate that the speaker recognition unit based on GMM-UBM achieves the best performance. Finally, five elderly persons are invited to measure the usability of the proposed system. A questionnaire is used to survey the five elderly persons, and the result indicates that the proposed system is highly potentially applicable in improving the interpersonal relationship of the elderly with MCI.

(1) Background: Older people hospitalized with Covid-19 can reduced the capacity to walk. However, the prevalence of impairment of ambulation capacity still need to be established. Objective: To estimate the prevalence and identify the risk factors associated with the impairment of ambulation capacity at hospital discharge of older people with Covid-19. (2) Methods: A retrospective cohort study. Included age &gt; 60 years, both sexes, hospitalized due to Covid-19. Clinical data was collected from the medical records. Ambulation capacity prior to Covid-19 infection was assessed through the patient report from his relatives. Multiple logistic regressions were performed to identify the risk factors associated with the impairment of ambulation at hospital discharge. (3) Results: Data from 429 older people were randomly. Among the 56.4% who were discharged, 57.9% had reduced ambulation capacity. Factors associated with reduced ambulation capacity at discharge were hospital stay higher than 20 days (OR: 3.5) and dependent ambulation capacity prior to Covid-19 (OR: 11.3). (4) Conclusion: More than half of the older people who survived hospitalized due to Covid-19 had reduced ambulation capacity at hospital discharge. Impaired ambulation prior to the infection, and a longer hospital stay were risks factors for reduced ambulation capacity.

The behavioral variant of frontotemporal dementia (bvFTD) has a devastating effect on multiple domains of daily living. The purpose of this PRISMA-compliant systematic review is to summarize the most important factors associated with functional impairment in this clinical group by critically analyzing the existing literature spanning the period from 2000 to 2023. To be included in the review, the study had to investigate any kind of correlates of functional status in bvFTD patients, using a previously validated instrument of functional assessment. Out of 40 articles assessed for eligibility, 18 met the inclusion criteria. The anatomical pattern of cerebral atrophy at baseline appeared to be the strongest predictor of the rate of functional decline over time, with the frontal-dominant anatomical subtype being associated with a faster rate of functional impairment. Additionally, executive dysfunction as well as apathy appeared to contribute significantly to functional disability in bvFTD patients. A comparative examination of bvFTD in relation to other clinical subtypes of FTD and other types of dementia in general suggests that it’s the predominant atrophy of the frontal lobes along with the subsequent unique combination of cognitive and neuropsychiatric manifestations that account for the pronounced functional limitations observed in these individuals, even from the early stages of the disease.

Diabetes is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of type 2 diabetic patients with MCI are linked to sarcopenia and/or its criterion remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, BMI, duration of diabetes, hypertension, dyslipidemia, smoking, drinking, eGFR, HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This is the first study to show that slow walking speed is a sole determinant for the presence of MCI in patients with type 2 diabetes. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus.

This article propose a didactic, through games, tool based on information and communication technologies, in order to eliminate possible communication barriers and to promote the inclusion of students with hearing impairment in Physical Education classes. To this end, a dossier of traditional games has been developed. These are structured in turn into objectives, materials, organisation, graphic description and a QR code for each game. These codes are linked to different videos hosted on the YouTube platform, in which the explanation of the games, mentioned above, can be visualised graphically using sign language. The whole creative process is described in the article, as well as possible pedagogical applications of the use of the tools created for this purpose in other educational contexts.

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. In the present study, we aimed to determine whether treatment with resveratrol reduces reactive oxygen species (ROS) generation in the brain, thereby reducing cognitive impairment in rats with angiotensin II (Ang-II)-induced early AD. Male WKY rats with Ang-II-induced AD were treated with losartan or resveratrol for 2 weeks. Our results revealed that treatment with resveratrol (10 mg/kg/day) decreased blood pressure, increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased ROS production in the nucleus tractus solitarius (NTS) in the Ang-II groups. In addition, inhibition of Tau^T231 phosphorylation in the hippocampus using resveratrol significantly abolished Ang-II-induced expression of Ab precursors, active caspase 3, and glycogen synthase kinase 3b (GSK-3b)^Y216 while increasing Akt^S473 phosphorylation. Notably, resveratrol reversed impairments in hippocampal-dependent contextual memory induced by deleting NADPH oxidase and NOX2. Overall, our results suggest that resveratrol exerts neuroprotective effects against memory impairment and hippocampal damage in a rat model of early stage AD by reducing oxidative stress. These novel findings indicate that resveratrol may represent a pharmacological option for patients with hypertension at a risk of AD during old age.

Sulfated polysaccharides from seaweed are highly active natural substances having valuable applications. In the present paper, attempts have been made to discuss the physicochemical and structural features of polysaccharides isolated from red marine alga Alsidium corallinum (ACPs) and its protective effect in hepatic impairments induced by tebuconazole (TBZ) in rats. Structural features were determined using High performance liquid chromatography, Fourier transformed infrared, and solid state ¹H and ¹³C-Nuclear magnetic resonance analysis. ACPs are found to be hetero-sulfated-anionic polysaccharides that contained carbohydrates, sulfate groups and uronic acids. In vitro biological activities suggested the effective antioxidant and antimicrobial capacities of ACPs. For antioxidant testing in vivo, the biochemical analysis and plasma profiles displayed that oral administration of ACPs could mitigate blood lipid indicators, including total cholesterol, triglyceride, low and high density lipoprotein cholesterol, bilirubin, liver function indexes involving alanine aminotransferase and aspartate aminotransferase, showed that ACPs possessed obvious antioxidant activities. Besides, the intervention of ACPs potentially inhibited lipid peroxidation, protein oxidation, key enzymes of lipid metabolism (<0.001) and increased levels and antioxidant status (<0.05). Histomorphological observation confirmed that ACPs intervention could partially repair liver injuries caused by TBZ. The computational results showed that A. corallinum monosaccharides bound 1JIJ, 1HD2 and 1WL4 receptors with acceptable affinities, which together with deep embedding and molecular interactions support the antioxidant, antimicrobial and hypolipidemic outlined effects in the in vitro and in vivo findings. In view of their prominent antioxidant effects, ACPs stand for promising candidates in liver diseases and need be considered in pharmaceutical applications.

Astragaloside IV (AIV) – triterpenoid saponin from the Astragalus mongholicus roots with the proved acetylcholinesterase (AChE)-inhibitory capability was used as the substance with the potential to attenuate memory impairment. Scopolamine (SCOP), antagonist of muscarinic cholinergic receptors and lipopolysaccharide (LPS), neuroinflammation inducer were used to impair memory processes in the passive avoidance (PA) test in mice. This memory impairment in the SCOP-treated mice was attenuated by the earlier intraperitoneal (ip) administration of AIV in the dose of 25 mg/kg. The reduction of memory impairment by LPS was not observed, therefore AIV does not reverse memory impairments through the anti-inflammatory mechanisms. All the studied doses of AIV did not affect basic locomotor activity of mice. As a result of the post-mortem analysis of mice body tissues, the largest content of AIV was determined in the kidneys, then in the spleen, liver and the smallest one in brain by mass spectrometry.

Background: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the ApoE gene and plasmatic apolipoprotein E (ApoE) levels as MCI biomarkers in Colombian subjects with MCI and controls. Methods: 100 participants were included (71% women, average age, 70 yrs., range 43-91). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Multivariate logistic regression models adjusted by age and gender were performed to examine the risk association of MCI with plasma ApoE and APOE methylation Results: MCI was diagnosed in 41 subjects (average age, 66.5±9.6 yrs.) and compared with 59 controls. Elevated plasma ApoE and APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (P<0.05). Higher CpG-227 methylation correlated with lower risk for MCI (P=0.002). Only CpG-227 was significantly correlated with plasmatic ApoE levels (correlation coefficient=-0.665; P=0.008). Conclusion: Differential APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns can be used as potential biomarkers to identify early stages of MCI.

Abstract: Letter migrations between words in reading aloud (e.g., reading "cane love" as "lane love" or "lane cove") are known to result from a deficit in the visual-orthographic analysis and characterize attentional dyslexia. In spontaneous speech, individuals with impairment in the phonological output buffer may show migrations of phonemes between words. The purpose of this study was to examine whether migrations between words in reading aloud can also result from a deficit in the phonological output buffer, to explore the characteristics of migrations resulting from orthographic input and from phonological output deficits, and to examine methods to distinguish these two sources. Using tasks of reading aloud of 92-182 word pairs, we identified 18 adults and adolescents with developmental dyslexia who made between-word letter migrations in reading aloud, significantly more than age-matched controls (372 adults and 26 7th-graders). To distinguish between orthographic-input and phonological-output sources for these migrations, we administered a test assessing orthographic-input without spoken-output (written-semantic-decision on 140 migratable word pairs) and a test of repetition of 36 auditorily-presented migratable word pairs, assessing spoken output without orthographic-input (and word span tests). These tests indicated that the migrations of ten of the participants with dyslexia resulted from an orthographic-input deficit, and for the other eight participants, migrations resulted from a phonological-output deficit. We identified several differences between the two types of between-word errors: first, whereas the individuals with attentional dyslexia made omissions of a letter that appeared in the same position in the two words, the phonological output buffer group did not make such omissions. In addition, the groups differed in the origin of migration: orthographic input migrations involve letters that are orthographically adjacent, whereas phonological output migrations involve phonemes that have just been spoken or that are prepared together in the phonological buffer for production. This was manifested in that migrations from the line below and from two lines above occurred only in the orthographic input deficit group, and migrations occurred from a word vertically close to the target in the orthographic input group but from a word that has just been spoken (placed diagonally to the target) in the phonological output group. This study thus indicates that between-word migrations in reading-aloud can result not only from attentional dyslexia, but also from a phonological output buffer deficit, and offers ways to distinguish between the two.

The aim of this study was to examine the prevalence of self-reported and parent-reported bullying victimization, perpetration, and victimization-perpetration and the associations of autistic social impairment and attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms with bullying involvement in adolescents with high functioning autism spectrum disorder (ASD). A total of 219 adolescents with high functioning ASD participated in this study. The associations of sociodemographic characteristics, parent-reported autistic social impairment on the Chinese Social Responsiveness Scale, and parent-reported ADHD and ODD symptoms on the Short form of the Swanson, Nolan, and Pelham Version IV Scale (SNAP-IV)-Chinese version with self-reported and parent-reported bullying victimization, perpetration, and victimization-perpetration evaluated using the Chinese version of the School Bullying Experience Questionnaire were examined using logistic regression analysis. The agreement between self-reported and parent-reported bullying involvement was low. Compared with bullying involvement experiences reported by adolescents themselves, parents reported higher rates of pure bullying victimization (23.7% vs. 17.8%) and victimization-perpetration (28.8% vs. 9.1%) but a lower rate of pure bullying perpetration (5.9% vs. 9.1%). Deficit in socio-communication increases the risk of being pure victims and victim-perpetrators. Parent-reported victim-perpetrators had more severe ODD symptoms than did parent-reported pure victims. The agreement between self-reported and parent-reported bullying involvement of adolescents with high functioning ASD was low. Deficit in socio-communication and ODD symptoms were significantly associated with a high risk of bullying involvement in adolescents with high functioning ASD.

Background: The Apolipoprotein E4 (ApoE4) genotype is strongly associated with Alzheimer’s disease (AD), although the presence of the ApoE4 allele alone is not sufficient to explain AD. The pathophysiology of amnestic mild cognitive impairment (aMCI) remains unclear. This study aims to examine associations between peripheral blood biomarkers coupled with ApoE4 and episodic and semantic memory. Methods: The CERAD battery was completed and various biomarkers were assayed in 60 subjects with aMCI, 60 with AD and 62 healthy controls. Results: Deficits in semantic and episodic memory were significantly predicted by anion gap and bicarbonate, albumin and glucose coupled with Apo E4. Furthermore, these peripheral biomarkers interacted with ApoE to predict greater memory impairments. Conclusions: Peripheral blood biomarkers may interact with pathways related to ApoE4 to predict greater semantic and episodic memory impairments, thus contributing to the pathophysiology of aMCI and AD. Our data suggest that the transition from aMCI to AD could at least in some cases be associated with significant interactions between ApoE4 and those peripheral blood biomarkers.

Blindness or visual impairment following congenital heart repair is a rare complication. It can be transient or permanent depending in underlying etiology and damage to optic pathway. We report first case of transient blindness following congenital heart repair due to unilateral subdural hematoma in occipital region.

Background: No studies have examined whether interactions between the apolipoprotein E4 (ApoE4) allele and peripheral biomarkers, hypertension, and type 2 diabetes mellitus (T2DM) may impact the neurocognitive, behavioral and social dysfunctions in amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Aims: To clinically define and biologically validate a subgroup of aMCI subjects that take up an intermediate position between controls and AD patients. Methods: In 61 healthy controls, 60 subjects with aMCI, and 60 AD patients we measured the features of aMCI/AD using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). A composite BIORISK score was computed using the ApoE4 allele, serum folate, albumin, white blood cells, fasting blood glucose (FBG), atherogenic index of plasma (AIP), T2DM and hypertension. Results: Clustering and nearest neighbour analyses were unable to validate the aMCI subgroup. We constructed two z unit-based composite scores, the first indicating overall burden of cognitive, social, and behavioural deterioration (OBD), and a second reflecting the interactions between ApoE4, all other biomarkers, hypertension and T2DM (BIORISK). We found that 40.2% of the variance in the OBD score was explained by BIORISK, ApoE4, age and education. The OBD index was used to construct three subgroups (normal, medium, and high OBD) with the medium group (n=45) showing mild cognitive dysfunctions (MCD) in memory, language, orientation, and ADL. People with MCD show OBD and BIORISK scores that are significantly different from controls and AD.Conclusions: Petersen’s aMCI criteria cannot be validated and should be replaced by the more restrictive, biologically validated MCD class.

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

A reduction of melatonin function contributes to the acceleration of Alzheimer's disease (AD), and understanding molecular processes of melatonin-related signaling is critical for intervention of AD progression. Recently, we synthesized and tested a series of melatonin derivates with donepezil fragments in silico and in vitro. In this study, one of the most potent compounds, 3c, was studied in an in vivo rat model of pinealectomy (pin) and subsequent icvAβ1-42 infusion. Melatonin was used as a referent drug. The treatment with melatonin and 3c (10 mg/kg, i.p. for 14 days) exerted a beneficial effect on memory decline and concomitant rise of Aβ1-42 and pTAU in the hippocampus in the pin + icvAβ1-42 rats. Melatonin supplementation facilitated the non-amyloidogenic signaling via a non-receptor (histone deacetylase sirtuin 1, SIRT1) and receptor-related signaling (MT/ERK/CREB). The hybrid 3c derivate up-regulated the MT1A and MT2B receptors, pERK and pCREB. Our findings strongly support the hypothesis that melatonin-related derivates may become a promising drug candidate in AD therapy.

There is increasing interest in identifying biological and imaging markers for the early detection of neurocognitive decline. In addition, non-pharmacological strategies including physical exercise and cognitive interventions may be beneficial for those developing cognitive impairment. The Feuerstein Instrumental Enrichment (FIE) Program is a cognitive intervention based on Structural Cognitive Modifiability and the Mediated Learning Experience (MLE) and aims to promote problem-solving strategies and metacognitive abilities. The FIE program uses a variety of instruments to enhance the cognitive capacity of the individual as a result of mediation. A specific version of the FIE program was developed for the cognitive enhancement of older adults, focusing on strengthening orientation skills, categorization skills, deductive reasoning and memory. We performed a prospective interventional pilot observational study on older subjects with MCI who participated in 30 mediated FIE sessions (two sessions weekly for 15 weeks). Of the 21 subjects who completed the study, there was a significant improvement in memory on the Neurotrax battery comparing pre- and post-intervention scores (pre: M=95.3, SD=12.2, post: M=101.2, SD=7.9, p<.05). Complete sets of anatomical MRI data for voxel-based morphometry, taken at the beginning and the end of the study, were obtained from 16 participants (mean age 83.5 years). Voxel-based morphometry showed an unexpected increase in grey matter (GM) in the anterolateral occipital border and the middle cingulate cortex. These initial findings of our pilot study support the design of randomized trials to evaluate the effect of cognitive training using the FIE Program on brain volumes and cognitive function.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.