Search Results (103)

Background: Out-of-hospital cardiac arrest (OHCA) survivors and their relatives may face challenges following hospital discharge, relating to mood, cognition, and returning to normal day-to-day activities. Identified research gaps include a lack of knowledge around what type of intervention is needed to best navigate recovery. In this study, we investigate the feasibility and patient acceptability of a new virtual psychoeducational group intervention for OHCA survivors and their relatives and compare it to a control group receiving a digital information booklet. Methods: V-CARE is a comparative, single-blind randomized pilot trial including participants at selected sites of the STEPCARE trial, in the United Kingdom and Sweden. Inclusion criteria are a modified Rankin Scale (mRS) ≤ 3 at 30-day follow-up; no diagnosis of dementia; and not experiencing an acute psychiatric episode. One caregiver per patient is invited to participate optionally. The intervention group in V-CARE receives four semi-structured, one-hour-long, psychoeducational sessions delivered remotely via video call by a trained clinician once a week, 2–3 months after hospital discharge. The sessions cover understanding cardiac arrest; coping with fatigue and memory problems; managing low mood and anxiety; and returning to daily life. The control group receives an information booklet focused on fatigue, memory/cognitive problems, mental health, and practical coping strategies. Results: Primary: feasibility (number of patients consented) and acceptability (retention rate); secondary: satisfaction with care (Client Satisfaction Questionnaire 8 item), self-management skills (Self-Management Assessment Scale) and, where available, health-related outcomes assessed in the STEPCARE Extended Follow-up sub-study including cognition, fatigue, mood, quality of life, and return to work. Conclusions: If preliminary insights from the V-CARE trial suggest the intervention to be feasible and acceptable, the results will be used to design a larger trial aimed at informing future interventions to support OHCA recovery. Full article

Alzheimer’s disease (AD) has become an increasingly pressing concern for the aging population. Current AD treatments mainly focus on cognitive and neuropsychiatric symptoms—with few FDA-approved treatments targeting disease progression itself. The amyloid cascade hypothesis describes the formation and accumulation of β-amyloid (Aβ) oligomers and plaques as a primary event in AD pathogenesis. This hypothesis has served as the foundation of disease-modifying treatment development over the last decade. Recently, glutaminyl cyclase (QC) has been identified as a potential drug target in the amyloid cascade. QC catalyzes the cyclization of Aβ to form pyroglutamated Aβ (pEAβ). pEAβ acts as the seed for the formation of Aβ plaques, thus preventing the formation of pEAβ via QC inhibition, and offers a promising therapeutic strategy against AD. Here, we offer an overview of the pathway QCI research has followed—from the initial testing of imidazole-based inhibitor scaffolds to QCI structural optimization via pharmacophore identification, Varoglutamstat entering clinical trials, and further avenues of bettering specificity and potency for future QCI development. Full article

Tau protein plays a pivotal role in maintaining neuronal structure and function through its regulation of microtubule stability and neuronal polarity. Encoded by the MAPT gene, Tau exists in multiple isoforms due to alternative mRNA splicing, with differential expression in the central and peripheral nervous systems. In healthy neurons, tau mRNA is selectively localized and translated in axons, a process tightly regulated by untranslated regions (UTRs) and RNA-binding proteins such as HuD and FMRP. Pathologically, Tau undergoes hyperphosphorylation, misfolding, and aggregation, which contribute to neurodegeneration in a range of disorders collectively known as tauopathies. Alzheimer’s disease (AD) is the most prevalent tauopathy, where abnormal Tau accumulation in the temporal and frontal lobes correlates with cognitive decline and behavioral symptoms. Other tauopathies, including Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), Frontotemporal Dementia with Parkinsonism (FTDP-17), and Pick’s disease, are distinguished by the predominance of specific Tau isoforms (3R or 4R), cellular distribution, and affected brain regions. Notably, astroglial tauopathies highlight the pathological role of Tau accumulation in glial cells, expanding the understanding of neurodegeneration beyond neurons. Despite advances in imaging biomarkers (e.g., Tau-PET) and molecular diagnostics, effective disease-modifying therapies for tauopathies remain elusive. Ongoing research targets Tau through immunotherapies, splicing modulators, kinase inhibitors, and antisense oligonucleotides, aiming to mitigate Tau pathology and its deleterious effects. Understanding the multifaceted roles of Tau in neuronal and glial contexts is critical for developing future therapeutic strategies against tauopathies. Full article

Background: Fatigue is a prevalent and debilitating symptom in people with multiple sclerosis (pwMS), significantly impairing quality of life. While the cerebellum is traditionally associated with motor control, emerging evidence suggests its involvement in cognitive, emotional, and integrative functions. This study aimed to explore the relationship between fatigue components (physical, cognitive, and psychosocial), clinical disability, and cerebellar structural changes in pwMS acquired via magnetic resonance imaging (MRI). Methods: Participants of this cross-sectional study underwent clinical assessments for fatigue (Modified Fatigue Impact Scale) and disability (Expanded Disability Status Scale). Cerebellar volumes were measured using high-resolution MRI and voxel-based morphometry (VBM) to identify correlations between fatigue subdomains and specific cerebellar subregions. Statistical analyses included group comparisons and correlation tests. Results: Forty-four pwMS were included. Fatigued MS patients exhibited reduced sensorimotor cerebellar volumes compared to non-fatigued counterparts. Physical fatigue correlated negatively with sensorimotor cerebellum volume, while cognitive fatigue showed an inverse relationship with limbic cerebellum regions. Interestingly, psychosocial fatigue was positively associated with limbic cerebellum volume, contrary to initial hypotheses. Higher disability scores were linked to atrophy in cognitive and limbic cerebellar regions. Conclusions: The findings highlight the cerebellum’s multifaceted role in MS-related fatigue, with distinct subregions contributing to physical, cognitive, and psychosocial fatigue components. These results underscore the cerebellum’s critical function as a hub for motor, cognitive, and emotional integration. Future longitudinal studies incorporating objective measures and advanced imaging are essential to elucidate these relationships further and inform targeted therapeutic strategies for pwMS. Full article

The International CCN Society has been organizing workshops and conferences for the past two decades to advance our understanding of the biology and pathophysiology of the cellular communication network (CCN) proteins. The 12th CCN Workshop broadened the scope of discussions, introducing topics like CCN-dependent and -independent signaling networks involved in brain development, cellular senescence, efferocytosis, neurobiology, and the application of DNA-fabricated origami structures. This expansion proved fruitful and should continue in future events. Fostering collaborations across various fields has created a dynamic environment for innovative ideas, driving substantial progress to tackle both basic scientific questions and clinically relevant challenges. Three standout presentations sparked significant discussions and highlighted key advancements in these areas. These include the work of Li-Jen Lee (Neurobiology and Cognitive Science Center, National Taiwan University) on the involvement of the CCN2 protein in depressive and aggressive behaviors in mice; the studies of Anna Zampetaki (King’s College London British Heart Foundation Centre, School of Cardiovascular & Metabolic Medicine and Sciences) and Brahim Chaqour (University of Pennsylvania, Perelman School of Medicine, Dept of Molecular Ophthalmology) on the metabolome and mechanosensing in iPSC-derived human blood vessel organoids and in the microvasculature of genetically modified mice, and the talk of Björn Högberg (Karolinska Institutet, Department of Medical Biochemistry and Biophysics) on the promises of DNA origami. We believe that these examples illustrate better future directions, as they offer an opportune moment to pursue initiatives that broaden the focus of the CCN Workshops and other projects like ARBIOCOM (website link included below) that support collaboration among research societies, educational institutions, and private biomedical industries, all working together to further our understanding of biosignaling and cellular communication networks for the development of new drug discovery methods and disease treatments. Full article

Background: Aging is a well-established independent risk factor for both cognitive impairment and sleep disorders, including obstructive sleep apnea (OSA), a modifiable yet underrecognized condition. OSA has been implicated in biological mechanisms contributing to Alzheimer’s disease, including amyloid-β accumulation, tau phosphorylation, and neuroinflammation. This underscores the need to optimize OSA diagnosis in individuals with an increased risk of dementia. Methods: This cross-sectional observational study enrolled adults aged 60–85 years with a CAIDE dementia risk score ≥6. Subjective sleep was evaluated using validated questionnaires (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and the Oviedo Sleep Questionnaire), while objective sleep data were obtained through a single-night peripheral arterial tonometry (PAT)-based wearable device, complemented by a 7-day sleep diary. Participants also completed the STOP-BANG and Berlin questionnaires, with clinically relevant findings communicated to participants. Results: Among 322 participants (48.8% women; mean age 71.4 ± 6.4 years), moderate-to-severe OSA (apnea–hypopnea index [AHI] ≥ 15) was identified in 48.49%, despite the absence of prior diagnoses. Subjective screening tools frequently underestimated OSA severity compared to objective assessments. While no significant sex-based differences were noted, higher AHI values correlated strongly with increased body mass index and elevated dementia risk scores. Conclusions: A marked discrepancy between subjective and objective sleep measurements complicates the accurate diagnosis and management of most sleep disorders, including OSA. Sleep disorders remain significantly underdiagnosed in individuals at increased risk for dementia. Integrating wearable technologies and structured tools such as sleep diaries into routine assessments can enhance diagnostic precision, enabling timely interventions for these modifiable risk factors of dementia. Full article

In this study, the impact of lentil hull soluble dietary fibers (SDFs) on colitis and behavioral deficits in mice was assessed. Structural characterizations of SDFs confirmed that cellulase-modified soluble dietary fiber exhibited better physicochemical properties: more porous microstructure; similar polysaccharide structure; more stable particle size distribution; higher crystallinity; better adsorption capacity; and lower viscosity. Additionally, we explored its potential cognitive benefits via the gut-brain axis by behavioral tests, histopathology, 16S rRNA sequencing, gas chromatography and metabolomics analysis. The results showed that SDFs significantly improved inflammatory symptoms in colon and brain and cognitive behaviors. LSDF had better efficacy than HSDF. LSDF intervention decreased the harmful bacteria abundance (Bacteroides, Flexispira and Escherichia, etc.) and increased beneficial bacteria abundance (Aggregatibacter and Helicobacter, etc.). LSDF also affected brain metabolites through the sphingolipid metabolism. Spearman correlation analysis showed that there was a positive correlation between harmful bacteria with inflammatory factors (LPS, IL-1β, IL-6, and TNF-α, etc.) and sphingolipid metabolites, while beneficial bacteria were positively correlated with brain-derived neurotrophic factor (BDNF), IL-10, and cognitive behavior. This study highlights the value of SDFs in future diet-based therapeutic strategies targeting gut-brain interactions. Full article

Neonatal encephalopathy suspected to be due to hypoxic ischaemic encephalopathy (NESHIE) carries the risk of death or severe disability (cognitive defects and cerebral palsy). Previous genetic studies on NESHIE have predominantly focused on exomes or targeted genes. The objective of this study was to identify genetic variants associated with moderate–severe NESHIE through whole-genome, unbiased analysis. Variant filtering and prioritization were performed, followed by association testing both on a case–control basis and to compare the grades of severity and/or progression. Association testing on neonates with NESHIE (N = 172) and ancestry-matched controls (N = 288) produced 71 significant genetic variants (false discovery rate corrected p-value < 6.2 × 10⁻⁴), all located in non-coding regions and not previously implicated in NESHIE. Disease-associated variants in non-coding regions are considered to affect regulatory functions, possibly by modifying gene expression, promoters, enhancers, or DNA structure. The most significant variant was at position 6:162010973 in the Parkin RBR E3 ubiquitin protein ligase (PRKN) intron. Intronic variants were also identified in genes involved in inflammatory processes (SLCO3A1), DNA repair (ZGRF1), synaptogenesis (CNTN5), haematopoiesis (ASXL2), and the transcriptional response to hypoxia (PADI4). Ten variants were associated with a higher severity or lack of improvement in NESHIE, including one in ADAMTS3, which encodes a procollagen amino protease with a role in angiogenesis and lymphangiogenesis. This analysis represents one of the first efforts to analyze whole-genome data to investigate the genetic complexity of NESHIE in diverse ethnolinguistic groups of African origin and provides direction for further study. Full article

Neurodegenerative disorders (NDs) cause progressive neuronal loss and are a significant public health concern, with NDs projected to become the second leading global cause of death within two decades. Huntington’s disease (HD) is a rare, progressive ND caused by an autosomal-dominant mutation in the huntingtin (HTT) gene, leading to severe neuronal loss in the brain and resulting in debilitating motor, cognitive, and psychiatric symptoms. Given the complex pathology of HD, biomarkers are essential for performing early diagnosis, monitoring disease progression, and evaluating treatment efficacy. However, the identification of consistent HD biomarkers is challenging due to the prolonged premanifest HD stage, HD’s heterogeneous presentation, and its multiple underlying biological pathways. This study involves a 10-year bibliometric analysis of HD biomarker research, revealing key research trends and gaps. The study also features a comprehensive literature review of emerging HD biomarkers, concluding the need for better stratification of HD patients and well-designed longitudinal studies to validate HD biomarkers. Promising candidate wet HD biomarkers— including neurofilament light chain protein (NfL), microRNAs, the mutant HTT protein, and specific metabolic and inflammatory markers— are discussed, with emphasis on their potential utility in the premanifest HD stage. Additionally, biomarkers reflecting brain structural deficits and motor or behavioral impairments, such as neurophysiological (e.g., motor tapping, speech, EEG, and event-related potentials) and imaging (e.g., MRI, PET, and diffusion tensor imaging) biomarkers, are evaluated. The findings underscore that the discovery and validation of reliable HD biomarkers urgently require improved patient stratification and well-designed longitudinal studies. Reliable biomarkers, particularly in the premanifest HD stage, are crucial for optimizing HD clinical management strategies, enabling personalized treatment approaches, and advancing clinical trials of HD-modifying therapies. Full article

Background: The segmentation of electroencephalography (EEG) signals into a limited number of microstates is of significant importance in the field of cognitive neuroscience. Currently, the microstate analysis algorithm based on global field power has demonstrated its efficacy in clustering resting-state EEG. The task-related EEG was extensively analyzed in the field of brain–computer interfaces (BCIs); however, its primary objective is classification rather than segmentation. Methods: We propose an innovative algorithm for analyzing task-related EEG microstates based on spatial patterns, Riemannian distance, and a modified deep autoencoder. The objective of this algorithm is to achieve unsupervised segmentation and clustering of task-related EEG signals. Results: The proposed algorithm was validated through experiments conducted on simulated EEG data and two publicly available cognitive task datasets. The evaluation results and statistical tests demonstrate its robustness and efficiency in clustering task-related EEG microstates. Conclusions: The proposed unsupervised algorithm can autonomously discretize EEG signals into a finite number of microstates, thereby facilitating investigations into the temporal structures underlying cognitive processes. Full article

The concept of cognitive reserve (CR) has been a cornerstone in cognitive aging research, offering a framework to explain how life experiences like education, occupation, bilingualism, and physical exercise may buffer individuals from cognitive decline in the face of aging or neurological disease. However, this paper argues that the CR model, while influential, may have outlived its usefulness due to inherent limitations that constrain future research directions and unintentionally encourage “magical thinking”. Specifically, CR’s definition, which relies on cognitive performance being “better than expected” based on known measures of brain structure and function, makes the concept temporally bound to current scientific understanding, potentially stifling novel insights into cognition. In contrast, we propose a shift to a cognitive capacity (CC) framework, which views cognitive performance as being always determined by the brain’s structural and functional capacities, without needing to invoke expectations based on incomplete knowledge. The CC framework is broader, encompassing factors that either promote or demote cognitive performance by directly modifying brain structure and function. This reconceptualization opens avenues for investigating cognitive enhancement not only in the context of aging or disease but also in young, healthy individuals. By emphasizing causal pathways between brain changes and cognitive outcomes, this perspective provides a more flexible and testable approach to understanding the mechanisms behind cognitive performance and its modulation across the lifespan. Full article

Background/Objectives: Traumatic craniomaxillofacial (CMF) injuries are associated with various symptoms/concerns that affect patients’ quality of life. The assessment of outcomes from the patient perspective has been limited by the absence of patient-reported outcome (PRO) measures tailored to this patient population. To address this need, we employed a mixed methods, multi-step process to first identify the most important symptoms/concerns and then use this information to construct a PRO symptom battery. Methods: CMF clinicians and patients who had sustained traumatic CMF injuries participated in semi-structured interviews to elicit the symptoms/concerns considered the most important. The data were analyzed using an iterative coding procedure and symptom/concern frequency was tabulated. The findings were used to develop a conceptual model of the most important symptoms to include in a PRO battery. Existing items were modified as needed and new items were drafted to ensure adequate coverage of the symptoms. Results: The resulting AO CMF Injury Symptom Battery includes four modules specific to the injury site (oral, ocular, nasopharyngeal, ear) and five universal modules (pain/sensation, cognitive, cosmetic, psychosocial, and injury impact). Conclusions: The AO CMF Injury Symptom Battery offers promise for assessing symptoms only patients can report on in clinical research and practice. Ongoing research will examine the battery’s psychometric properties. Full article

Background and Objectives: Cognitive impairment is defined as a reduced ability to perform one or more cognitive functions, potentially leading to dementia if the condition worsens. With dementia being a rapidly growing public health issue affecting approximately 50 million people worldwide, understanding modifiable risk factors such as thyroid disease is crucial for prevention and early diagnosis. Thyroid hormones play a vital role in brain development and functioning, impacting processes such as neuron growth, myelination, and neurotransmitter synthesis. Recent decades have seen thyroid disorders emerging as potential independent risk factors for reversible cognitive impairment. Materials and Methods: The review adheres to PRISMA guidelines, utilizing a structured PICO question to explore whether individuals with thyroid diseases have a higher risk of developing dementia and cognitive impairments compared to those without. The literature search was conducted in PubMed, Cochrane, and ScienceDirect databases, including studies published from 1 January 2019 to 31 December 2023. The literature review discusses nine selected articles. Results: The findings highlight a complex association between thyroid dysfunction and cognitive decline, with some studies indicating significant links, particularly with hypothyroidism, and others suggesting the relationship may depend on the specific type of thyroid dysfunction or cognitive domain affected. Six out of nine articles found a link between thyroid disease and cognitive impairment, while three articles refuted this link. Conclusions: The review reveals a complex and ambiguous relationship between thyroid dysfunction and cognitive impairment. Further research is needed to elucidate the mechanisms underlying these associations and to determine whether thyroid dysfunction may be a modifiable risk factor for dementia. Full article

This paper is devoted to an experimental investigation of cognitive contextuality inspired by quantum contextuality research. This contextuality is related to, but not identical to context-sensitivity which is well-studied in cognitive psychology and decision making. This paper is a part of quantum-like modeling, i.e., exploring the methodology of quantum theory outside of physics. We examined the bistable perception of cup-like objects, which strongly depends on experimental contexts. Our experimental data confirmed the existence of cognitive hysteresis, the important role of memory, and the non-commutative structure of cognitive observables. In physics, quantum contextuality is assessed using Bell-CHSH inequalities, and their violation is incorrectly believed to imply the nonlocality of Nature. The violation of Bell-type inequalities in cognitive and social science strongly indicates that the metaphysical implications of these inequalities are quite limited. In our experiments, modified Leggett–Garg inequalities were also significantly violated, but this only means that experimental data from experiments performed in different contexts cannot be modeled by a unique set of noncontextual, jointly distributed random variables. In our experiments, we know the empirical probability distributions measured in different contexts; thus, we can obtain much more detailed and reliable information about contextuality in human cognition by performing nonparametric compatibility tests. Full article

Objective: High-density lipoprotein cholesterol efflux function may prevent brain amyloid beta deposition and neurodegeneration. However, the relevance of this finding has not been established in the diverse middle-aged population. Methods: We examined 1826 adults (47% Black adults) who participated in the Dallas Heart Study to determine associations between high-density lipoprotein (HDL) measures and brain structure and function. White matter hyperintensities (WMH) and whole-brain grey matter volume (GMV) were measured using brain MRI, and the Montreal Cognitive Assessment (MoCA) was used to measure neurocognitive function. HDL cholesterol efflux capacity (HDL-CEC) was assessed using fluorescence-labeled cholesterol efflux from J774 macrophages, and HDL particle size measures were assessed using nuclear magnetic resonance (NMR) spectroscopy (LipoScience). Multivariable linear regressions were performed to elucidate associations between HDL-CEC and brain and cognitive phenotypes after adjustment for traditional risk factors such as age, smoking status, time spent in daily physical activity, and education level. Results: Higher HDL-CEC and small HDL particle (HDL-P) concentration were positively associated with higher GMV normalized to total cranial volume (TCV) (GMV/TCV) after adjustment for relevant risk factors (β = 0.078 [95% CI: 0.029, 0.126], p = 0.002, and β = 0.063 [95% CI: 0.014, 0.111], p = 0.012, respectively). Conversely, there were no associations between HDL measures and WMH or MoCA (all p > 0.05). Associations of HDL-CEC and small HDL-P with GMV/TCV were not modified by ApoE-ε4 status or race/ethnicity. Interpretation: Higher HDL cholesterol efflux and higher plasma concentration of small HDL-P were associated with higher GMV/TCV. Additional studies are needed to explore the potential neuroprotective functions of HDL. Full article