Search Results (110)

Background: The cerebral compliance (or compensatory reserve) index, RAP, is a critical yet underutilized physiological marker in the management of moderate-to-severe traumatic brain injury (TBI). While RAP offers promise as a continuous bedside metric, its broader cerebral physiological context remains partly understood. This study aims to characterize the burden of impaired RAP in relation to other key components of cerebral physiology. Methods: Archived data from 379 moderate-to-severe TBI patients were analyzed using descriptive and threshold-based methods across three RAP states (impaired, intact/transitional, and exhausted). Agglomerative hierarchical clustering, principal component analysis, and kernel-based clustering were applied to explore multivariate covariance structures. Then, high-frequency temporal analyses, including vector autoregressive integrated moving average impulse response functions (VARIMA IRF), cross-correlation, and Granger causality, were performed to assess dynamic coupling between RAP and other physiological signals. Results: Impaired and exhausted RAP states were associated with elevated intracranial pressure (p = 0.021). Regarding AMP, impaired RAP was associated with elevated levels, while exhausted RAP was associated with reduced pulse amplitude (p = 3.94 × 10⁻⁹). These two RAP states were also associated with compromised autoregulation and diminished perfusion. Clustering analyses consistently grouped RAP with its constituent signals (ICP and AMP), followed by brain oxygenation parameters (brain tissue oxygenation (PbtO₂) and regional cerebral oxygen saturation (rSO₂)). Cerebral autoregulation (CA) indices clustered more closely with RAP under impaired autoregulatory states. Temporal analyses revealed that RAP exhibited comparatively stronger responses to ICP and arterial blood pressure (ABP) at 1-min resolution. Moreover, when comparing ICP-derived and near-infrared spectroscopy (NIRS)-derived CA indices, they clustered more closely to RAP, and RAP demonstrated greater sensitivity to changes in these ICP-derived CA indices in high-frequency temporal analyses. These trends remained consistent at lower temporal resolutions as well. Conclusion: RAP relationships with other parameters remain consistent and differ meaningfully across compliance states. Integrating RAP into patient trajectory modelling and developing predictive frameworks based on these findings across different RAP states can map the evolution of cerebral physiology over time. This approach may improve prognostication and guide individualized interventions in TBI management. Therefore, these findings support RAP’s potential as a valuable metric for bedside monitoring and its prospective role in guiding patient trajectory modeling and interventional studies in TBI. Full article

Introduction: Mild traumatic brain injury (mTBI) in older adults (≥65 years) is often underestimated, despite being associated with significant morbidity. Age-related vulnerability, comorbidities, and medication use may exacerbate outcomes. This study aimed to identify predictors of brain health and functional recovery in older adults following mTBI, focusing on acute symptoms, CT imaging findings, and sociodemographic factors. Methods: We analyzed a cohort of 93 older adult patients with mTBI (GCS 13–15) who were prospectively enrolled at a tertiary neurosurgical center. All patients underwent baseline CT, structured clinical assessment, and follow-up at six months with standardized instruments (Glasgow Outcome Scale–Extended-GOSE, 12-Item Short Form Health Survey (quality-of-life measure)-SF-12, Rivermead Post-Concussion Symptoms Questionnaire-RPQ, Patient Health Questionnaire-9 (depression measure)-PHQ-9, PTSD (Post Traumatics Stress Disorder) Checklist for DSM (Diagnostic and Statistical Manual for Mental Disorders)-PCL-5, Timed up and Go Test (mobility measure-TUG test). Multivariate regression was performed to identify independent predictors of recovery. Results: At six months, 94.9% of older adults achieved functional independence (GOSE ≥ 5), though only 43% attained complete recovery (GOSE = 8). Patients with acute intracranial lesions on CT had worse physical outcomes, including slower mobility (mean TUG 17.6 vs. 16.3 s, p = 0.012). Severe acute headache independently predicted poorer recovery (lower GOSE and SF-12 PCS). Lower educational attainment correlated with worse functional and quality-of-life outcomes, consistent with reduced cognitive reserve. Psychological outcomes (PTSD and depression rates) were not associated with CT findings but were influenced by social support and sex. Prompt anticoagulation reversal in patients on anticoagulants markedly reduced hemorrhagic complications. Discussion: Older adults with mTBI generally maintain independence but experience reduced physical health and mobility compared to younger patients. Predictors of poorer outcomes include severe acute symptoms, CT-detected lesions, advanced age, and lower educational levels. Psychosocial support mitigated mental health complications. Conclusions: mTBI in older adults is not benign. Clinical, imaging, and sociodemographic factors collectively shape recovery. Early identification of high-risk patients and targeted interventions are essential to preserve brain health and independence in this growing population. Full article

Malnutrition afflicts millions of the world’s children and predisposes to death from diarrhea and infectious diseases. Children with severe acute malnutrition (SAM) are at highest risk. Our review of the endocrinology and metabolomics of SAM implicates critical roles for white adipose tissue and its regulatory hormones and growth factors in the adaptation to nutritional deprivation and the restoration of metabolic homeostasis: white adipose provides substrates and energy for hepatic glucose production and cardiopulmonary and central nervous system function, and products of fat metabolism inhibit muscle glucose uptake and utilization and spare muscle protein. Collectively, these effects maintain glucose availability for the brain, red blood cells, and renal medulla and conserve muscle mass. White adipose tissue also secretes leptin, which facilitates the immune response and may protect against mortality from infection. Euglycemia and survival in SAM are thereby prioritized over linear growth, which is suppressed owing to inhibition of insulin-like growth factor 1 production and action. Diversion of energy from growth serves to maintain essential bodily functions in critically ill malnourished children, who have limited energy reserves. Thus, short-term reductions in growth rate have adaptive benefits in SAM. Under favorable conditions, clinical and metabolic recovery are accompanied by catch-up growth, which can mitigate, and in many cases reverse, the stunting of growth in childhood. Nevertheless, clinical recovery can be complicated by preferential accrual of central fat and a relative deficiency of lean/skeletal mass, with potential long-term complications including insulin resistance, glucose intolerance, and metabolic syndrome. Full article

Exercise-induced hypertension (EIH) has increasingly been observed among middle-aged long-distance runners, raising concerns about cardiovascular risk. This study aimed to investigate acute changes in cardiovascular biomarkers associated with vascular inflammation, oxidative stress, antioxidant defense, endothelial function, and myocardial burden in runners with EIH. Thirty-seven middle-aged male runners (aged 40–65 years) were categorized into a normal blood pressure group (NBPG; systolic blood pressure <210 mmHg, n = 23) and an EIH group (EIHG; ≥210 mmHg, n = 14) based on maximal systolic blood pressure during a graded exercise test (GXT). Participants performed a 30 min treadmill run at 80% heart rate reserve, and blood samples were collected before and after exercise. The biomarkers analyzed included high-sensitivity C-reactive protein (hs-CRP), derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), nitric oxide (NO), superoxide dismutase (SOD), and N-terminal pro-brain natriuretic peptide (NT-proBNP). The results show that the EIHG exhibited increased NT-proBNP and SOD levels, along with a reduced NO response, indicating elevated myocardial stress and impaired vasodilation. hs-CRP was positively correlated with multiple hemodynamic indices, and SOD levels were associated with maximal systolic pressure and myocardial burden. These findings highlight the need for individualized monitoring and cardiovascular risk management in runners with EIH. Full article

Background and Clinical Significance: Pituitary apoplexy is an extremely rare condition in children and adolescents with a rapid onset due to acute hemorrhage, infarction, or both in the pituitary gland. Most frequently, pituitary apoplexy is an asymptomatic or subclinical entity. Few cases of pituitary apoplexy with concurrent SARS-CoV-2 infection or COVID-19 vaccination have been reported. Case Presentation: We present the case of a 13-year-8-month-old boy who presented in our pediatric endocrinology department for the evaluation of short stature. He was previously diagnosed with secondary hypothyroidism and was treated with levothyroxine. At admission, clinical examination revealed a height of 141 cm (−2.68 SD/−2.4 SD corrected for mid-parental height), normal weight (60th centile), Tanner-stage G2P1, and delayed bone age. Basal IGF1 was normal, but the tests performed to assess the GH reserve confirmed the GH deficiency (peak GH value 3.11 ng/mL after clonidine/0.95 ng/mL after insulin). The brain MRI revealed a subacute pituitary hemorrhage. Thrombophilia and coagulopathies were excluded by further testing. Anti-SARS-CoV-2 (anti-S-protein IgG) antibodies (>200 BAU/mL) were compatible with COVID-19 infection, indicating a possible association between these two entities. At 3-month follow-up, physical examination showed a 3 cm height gain and advancing pubertal development (G4P2). Newer MRI found changes consistent with resolving hemorrhage. The patient was provided immediately with recombinant human GH and aromatase inhibitor therapy to maximize GH treatment response. During follow-up, the rGH dose was adjusted based on IGF1 values, and after 3 years and 10 months, rGH treatment was stopped, reaching a height of 172.3 cm (−0.51 SD) and surpassing the initial prediction of 164.5 cm. Conclusions: Pituitary apoplexy, an even rarer complication in the pediatric population, may be associated with SARS-CoV-2 infection. Further studies are necessary to better understand the intertwining of those conditions. Full article

Traumatic brain injuries (TBIs) are a serious problem affecting individuals of all ages. Mitochondrial dysfunctions represent a significant form of secondary injury and may serve as a promising target for therapeutic intervention. Our research demonstrated that craniotomy, which precedes the experimental induction of trauma in mice, can cause considerable damage to mitochondrial DNA (mtDNA), disrupt the regulatory expression of angiogenesis, and increase inflammation. However, the reduction in the mtDNA copy number and glial activation occur only after a direct impact to the brain. We explored two potential therapeutic agents: the dietary supplement L-carnitine—a potential reserve source of ATP for the brain—and the cardiac drug mildronate, which inhibits L-carnitine but activates alternative compensatory pathways for the brain to adapt to metabolic disturbances. We found that L-carnitine injections could protect against mtDNA depletion by promoting mitochondrial biogenesis. However, they also appeared to aggravate inflammatory responses, likely due to changes in the composition of the gut microbiome. On the other hand, mildronate enhanced the expression of genes related to angiogenesis while also reducing local and systemic inflammation. Therefore, both compounds, despite their opposing metabolic effects, have the potential to be used in the treatment of secondary injuries caused by TBI. Full article

Over 400 articles on the pathophysiology of brain aging, neuroaging, and neurodegeneration were reviewed, with a focus on epigenetic mechanisms and numerous non-coding RNAs. In particular, this review the accent is on microRNAs, the discovery of whose pivotal role in gene regulation was recognized by the 2024 Nobel Prize in Physiology or Medicine. Aging is not a gradual process that can be easily modeled and described. Instead, multiple temporal processes occur during aging, and they can lead to mosaic changes that are not uniform in pace. The rate of change depends on a combination of external and internal factors and can be boosted in accelerated aging. The rate can decrease in decelerated aging due to individual structural and functional reserves created by cognitive, physical training, or pharmacological interventions. Neuroaging can be caused by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle, and environmental factors, which are especially noticeable in space environments where adaptive changes can trigger aging-like processes. Numerous candidate molecular biomarkers specific to neuroaging need to be validated to develop diagnostics and countermeasures. Full article

The purpose of this study is analyse the differences in cognitive health, geriatric fitness, and brain activity between female elderly people with and without mild cognitive impairment (MCI) to contribute to the development of strategies for the prevention and management of MCI. The study included 56 female elderly residents of G city, and the participants were divided into an MCI group (32) and a non-MCI group (24). Cognitive health was assessed by an MMSE, and geriatric physical fitness was measured by various indicators such as strength, flexibility, and balance ability. Brain activity was measured by EEG(Electroencephalogram) to record concentration, stress, and left and right brain activity. Data were processed using independent samples t-tests and multiple regression analyses. The results showed that the MCI group was older, had more chronic diseases, and had a lower MMSE scores compared to the non-MCI group. In geriatric fitness measures, the non-MCI group had higher scores in handgrip strength and balance ability. In brain activity analyses, the MCI group had higher workloads and left brain activity than the non-MCI group, but there was no significant correlation with overall cognitive health. Regression analyses showed that, among the elderly physical fitness variables, vigour had a significant effect on cognitive health, suggesting that physical robustness may enhance cognitive reserve. The MCI group had lower cognitive health and physical fitness compared to the non-MCI group and showed some differences in brain activity. In particular, handgrip strength had a significant effect on cognitive health, suggesting that an exercise programme focused on strength training may be an effective intervention for the prevention and management of MCI. Full article

Goal: Current methodologies for assessing cerebral compliance using pressure sensor technologies are prone to errors and issues with inter- and intra-observer consistency. RAP, a metric for measuring intracranial compensatory reserve (and therefore compliance), holds promise. It is derived using the moving correlation between intracranial pressure (ICP) and the pulse amplitude of ICP (AMP). RAP remains largely unexplored in cases of moderate to severe acute traumatic neural injury (also known as traumatic brain injury (TBI)). The goal of this work is to explore the general description of (a) RAP signal patterns and behaviors derived from ICP pressure transducers, (b) temporal statistical relationships, and (c) the characterization of the artifact profile. Methods: Different summary and statistical measurements were used to describe RAP’s pattern and behaviors, along with performing sub-group analyses. The autoregressive integrated moving average (ARIMA) model was employed to outline the time-series structure of RAP across different temporal resolutions using the autoregressive (p-order) and moving average orders (q-order). After leveraging the time-series structure of RAP, similar methods were applied to ICP and AMP for comparison with RAP. Finally, key features were identified to distinguish artifacts in RAP. This might involve leveraging ICP/AMP signals and statistical structures. Results: The mean and time spent within the RAP threshold ranges ([0.4, 1], (0, 0.4), and [−1, 0]) indicate that RAP exhibited high positive values, suggesting an impaired compensatory reserve in TBI patients. The median optimal ARIMA model for each resolution and each signal was determined. Autocorrelative function (ACF) and partial ACF (PACF) plots of residuals verified the adequacy of these median optimal ARIMA models. The median of residuals indicates that ARIMA performed better with the higher-resolution data. To identify artifacts, (a) ICP q-order, AMP p-order, and RAP p-order and q-order, (b) residuals of ICP, AMP, and RAP, and (c) cross-correlation between residuals of RAP and AMP proved to be useful at the minute-by-minute resolution, whereas, for the 10-min-by-10-min data resolution, only the q-order of the optimal ARIMA model of ICP and AMP served as a distinguishing factor. Conclusions: RAP signals derived from ICP pressure sensor technology displayed reproducible behaviors across this population of TBI patients. ARIMA modeling at the higher resolution provided comparatively strong accuracy, and key features were identified leveraging these models that could identify RAP artifacts. Further research is needed to enhance artifact management and broaden applicability across varied datasets. Full article

Acute ischemic stroke (AIS) is frequently associated with long-term post-stroke cognitive impairment (PSCI) and dementia. While the mechanisms behind PSCI are not fully understood, the brain and cognitive reserve concepts are topics of ongoing research exploring the ability of individuals to maintain intact cognitive performance despite ischemic injuries. Brain reserve refers to the brain’s structural capacity to compensate for damage, with markers like hippocampal atrophy and white matter lesions indicating reduced reserve. Cognitive reserve involves the brain’s ability to optimize performance and use alternative networks to maintain function. Advanced methods of MRI and EEG processing may better assess brain reserve and cognitive reserve, with emerging predictive models integrating these measures to improve PSCI prediction. This article provides the design of a hospital-based study investigating the predictive role of functional connectivity and MRI radiomics in assessing PSCI occurrence one year after AIS. One hundred forty-four patients will be enrolled following strict inclusion/exclusion criteria. The patients will undergo comprehensive assessments, including neuropsychological testing, brain MRI, and quantitative EEG (QEEG), across four visits over a year. The primary outcome will be PSCI occurrence, and it will be assessed at six and twelve months after AIS. Secondary outcomes will include PSCI severity, recurrent AIS, and mortality. Statistical analyses will be performed to identify predictive factors using Cox proportional hazards models, and predictive models based on QEEG, MRI radiomics, and clinical data will be built. Early detection of AIS patients prone to developing PSCI might outline more effective therapeutic approaches, reducing the social and economic burden of ischemic stroke. Full article

Background: Sleep plays a crucial role in cognitive performance and cognitive changes in aging. In the current study, we investigated the role of sleep duration genetics in cognitive changes over time and the moderating effect of age. Methods: Participants were drawn from the Reference Abilities Neural Network and the Cognitive Reserve studies of Columbia University. Each participant underwent an evaluation of sleep function and an extensive neuropsychological assessment. Published GWAS summary statistics from a polygenic score for sleep duration (Sleep PGI) were used to derive Sleep PGI in our study. We examined whether this Sleep PGI is associated with cognitive changes over a 5-year follow-up and if age moderates this effect. Analysis was performed after first being adjusted for age group (young: 20–44; middle: 45–64; old: 65–80), sex, education, the first four principal components, intracranial volume (ICV), mean cortical thickness, and total gray matter volume. We included ICV, mean thickness, and total gray matter volumes as time-varying covariates. We further included interactions of time with age and the first four PCs. Results: A total of 96 white-only participants were included, aged 24 to 78 years old. In the fully adjusted model, age-specific analysis showed that in younger individuals, higher Sleep PGI was associated with lower rates of cognitive decline in speed of processing. Conclusion: Genetic variants associated with sleep duration significantly influence performance in speed of processing, with age playing a critical moderating role, over and above brain morphometry. A genetic predisposition for longer sleep duration can work as a protective factor against decline in the speed of processing in young adults. 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

Numerous encryption methods have been published to secure IoT devices in the last decade. Existing encryption methods still have disadvantages when it comes to securing IoT devices. On the other hand, a new encryption method using brain signals in IoT devices is gaining attention as a new solution. The encryption method based on brain signals essentially involves a hypothesis called imposed recall based on ironic process theory. The imposed recall was created with the expectation that imposing a specific choice on the subjects during the acquisition of brain signals would allow for better separation of EEG data. This paper presents experiments and approaches to prove the validity of the imposed recall hypothesis. With the experiments, the effects of ironic process theory on brain signal-based encryption can be observed. While performing the tests, varying approaches, including Granger causality, were applied to analyze the results. The results show that the imposed recall hypothesis can successfully reconstruct EEG data. The structured signals were determined to be effective in capturing matches of brain signals on subjects at different time intervals. Thus, the imposed recall hypothesis can be used in various fields, such as authentication, questioning, and identification, by reserving brain signals to be obtained from individuals. In addition, it was reported that it is possible to acquire the ability to provide security in both devices with limited hardware, such as IoT devices or complex systems. Full article

Background: In response to the rising mental health concerns and cognitive decline associated with the human brain’s neurogenesis, which continues until the tenth decade of life but declines with age and is suppressed by poor environments, this pilot study investigates how physical environments may influence public health proxy measures of neurogenesis in humans. This pilot study focuses on the residential environment where people spend most of their time and age in place, exploring the dependency of depression, anxiety, and cognitive impairment variations on spatial and lifestyle variables. Methods: A total of 142 healthy adults in England completed a survey consisting of PHQ-8, GAD-7, and CFI questionnaires and other questions developed to capture the variance in spatial and lifestyle factors such as time spent at home, house type layout complexity, spaciousness, physical activity, routine and spatial novelty, and perceived loneliness. Results: Extensive time spent at home has adverse effects on all measures, while multi-storey houses perform better than single-story houses with positive correlations with physical activity and spatial novelty. Separate regression models on the variance in depression, as the most salient dependent variable and reliably associated with neurogenesis, reveal that getting out of the house explains 20.5% of the variance in depression symptoms. At the scale of the house, multi-storey houses explain 16.5% of the variance. Both percentages are closer to the effect of loneliness, which we found to explain 26.6% of the variance in depression. Conclusions: The built environment appears to be significantly associated with changes in cognitive function and mental health symptoms associated with neurogenesis. This pilot study shows the equally important effect of physical and social enrichment, offering critically needed insights for neuroarchitecture and brain health research that is interested in public health. Full article

In mammals, the maintenance of energy homeostasis relies on complex mechanisms requiring tight synchronization between peripheral organs and the brain. Thyroid hormones (THs), through their pleiotropic actions, play a central role in these regulations. Hypothyroidism, which is characterized by low circulating TH levels, slows down the metabolism, which leads to a reduction in energy expenditure as well as in lipid and glucose metabolism. The objective of this study was to evaluate whether the metabolic deregulations induced by hypothyroidism could be avoided through regulatory mechanisms involved in metabolic flexibility. To this end, the response to induced hypothyroidism was compared in males from two mouse strains, the wild-derived WSB/EiJ mouse strain characterized by a diet-induced obesity (DIO) resistance due to its high metabolic flexibility phenotype and C57BL/6J mice, which are prone to DIO. The results show that propylthiouracil (PTU)-induced hypothyroidism led to metabolic deregulations, particularly a reduction in hepatic lipid synthesis in both strains. Furthermore, in contrast to the C57BL/6J mice, the WSB/EiJ mice were resistant to the metabolic dysregulations induced by hypothyroidism, mainly through enhanced lipid metabolism in their adipose tissue. Indeed, WSB/EiJ mice compensated for the decrease in hepatic lipid synthesis by mobilizing lipid reserves from white adipose tissue. Gene expression analysis revealed that hypothyroidism stimulated the hypothalamic orexigenic circuit in both strains, but there was unchanged melanocortin 4 receptor (Mc4r) and leptin receptor (LepR) expression in the hypothyroid WSB/EiJ mice strain, which reflects their adaptability to maintain their body weight, in contrast to C57BL/6J mice. Thus, this study showed that WSB/EiJ male mice displayed a resistance to the metabolic dysregulations induced by hypothyroidism through compensatory mechanisms. This highlights the importance of metabolic flexibility in the ability to adapt to disturbed circulating TH levels. Full article