Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis.

OBJECTIVE: The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression. METHODS: Through the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n = 343), along with controls, for a total sample size of n = 540, to replicate and extend prior findings in the study of TBI brain age. Cross-sectional T1w-MRI data were aggregated across 7 cohorts, and brain age was established using a similar brain age algorithm to prior work in TBI. RESULTS: Findings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find strong evidence supporting a link between PAD and cognitive performance. INTERPRETATION: This work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability in brain morphometry, eventually leading to further changes in the decades after a single cmsTBI. ANN NEUROL 2024;96:365-377.

The state of health in the European Union (EU-27) in 2019: a systematic analysis for the Global Burden of Disease study 2019.

BACKGROUND: The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This paper reports estimates of disease burden in the EU and individual 27 EU countries in 2019, and compares them with those in 2010. METHODS: We used the Global Burden of Disease 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardised death, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) rates for Level 2 causes, as well as life expectancy and healthy life expectancy (HALE). RESULTS: In 2019, the age-standardised death and DALY rates in the EU were 465.8 deaths and 20,251.0 DALYs per 100,000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases in age-standardised death and YLL rates across EU countries. However, YLD rates remained mainly unchanged. The largest decreases in age-standardised DALY rates were observed for "HIV/AIDS and sexually transmitted diseases" and "transport injuries" (each -19%). "Diabetes and kidney diseases" showed a significant increase for age-standardised DALY rates across the EU (3.5%). In addition, "mental disorders" showed an increasing age-standardised YLL rate (14.5%). CONCLUSIONS: There was a clear trend towards improvement in the overall health status of the EU but with differences between countries. EU health policymakers need to address the burden of diseases, paying specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease.

Accuracy of clinical diagnosis of behavioural variant frontotemporal dementia: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Behavioural variant frontotemporal dementia (bvFTD) characterisation has evolved, but diagnosis remains challenging, relying on clinical diagnostic criteria that have undergone revisions over time. In this systematic review, our aims are to evaluate the accuracy of clinical diagnostic criteria for bvFTD by comparing them against pathological diagnoses and determine potential improvement in performance over the years. METHODS AND ANALYSIS: This systematic review protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines and is registered on PROSPERO. We will search four databases (MEDLINE-PubMed, Web of Science, Embase and LILACS) using tailored search terms on May 1st 2024. Inclusion criteria encompass peer-reviewed articles reporting diagnostic parameters or raw data regarding bvFTD clinical diagnosis based on well-defined criteria. Screening and selection of relevant articles will be independently performed by two reviewers using the Covidence systematic review manager. Discrepancies will be resolved by a third researcher. Pathologic and genetic diagnosis will be the main gold standard, but we will also consider refined diagnoses after a follow-up period. Data will be collected on study design, baseline demographics and sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy. Study quality will be assessed with Quality Assessment of Diagnostic Accuracy Studies-2. If possible, we will conduct a meta-analysis using bivariate random-effect models. Subgroup analyses will consider study settings, gold standards, disease stages and bias. ETHICS AND DISSEMINATION: Ethics approval will not be needed because the data used in this systematic review will be extracted from published studies. Findings will be disseminated through peer-reviewed publications and presentations at relevant scientific conferences, potentially enhancing our understanding of bvFTD clinical diagnosis reliability and guiding future criteria refinements. PROSPERO REGISTRATION NUMBER: CRD42023389063.

The Prognostic Role of Candidate Serum Biomarkers in the Post-Acute and Chronic Phases of Disorder of Consciousness: A Preliminary Study.

INTRODUCTION: Serum biomarkers, such as Neurofilament Light (NF-L), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase (UCH-L1), and Total-tau (T-Tau) have been proposed for outcome prediction in the acute phase of severe traumatic brain injury, but they have been less investigated in patients with prolonged DoC (p-DoC). METHODS: We enrolled 25 p-DoC patients according to the Coma Recovery Scale-Revised (CRS-R). We identified different time points: injury onset (t0), first blood sampling at admission in Neurorehabilitation (t1), and second blood sampling at discharge (t2). Patients were split into improved (improved level of consciousness from t1 to t2) and not-improved (unchanged or worsened level of consciousness from t1 to t2). RESULTS: All biomarker levels decreased over time, even though each biomarker reveals typical features. Serum GFAP showed a weak correlation between t1 and t2 (p = 0.001), while no correlation was observed for serum NF-L (p = 0.955), UCH-L1 (p = 0.693), and T-Tau (p = 0.535) between t1 and t2. Improved patients showed a significant decrease in the level of NF-L (p = 0.0001), UCH-L1 (p = 0.001), and T-Tau (p = 0.002), but not for serum GFAP (p = 0.283). No significant statistical differences were observed in the not-improved group. CONCLUSIONS: A significant correlation was found between the level of consciousness improvement and decreased NF-L, UCH-L1, and T-Tau levels. Future studies on the association of serum biomarkers with neurophysiological and neuroimaging prognostic indicators are recommended.

MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study.

Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE.

The Use of Biofluid Markers to Evaluate the Consequences of Sport-Related Subconcussive Head Impact Exposure: A Scoping Review.

BACKGROUND: Amidst growing concern about the safety of sport-related repetitive subconcussive head impacts (RSHI), biofluid markers may provide sensitive, informative, and practical assessment of the effects of RSHI exposure. OBJECTIVE: This scoping review aimed to systematically examine the extent, nature, and quality of available evidence from studies investigating the effects of RSHI on biofluid markers, to identify gaps and to formulate guidelines to inform future research. METHODS: PRISMA extension for Scoping Reviews guidelines were adhered to. The protocol was pre-registered through publication. MEDLINE, Scopus, SPORTDiscus, CINAHL, PsycINFO, Cochrane Library, OpenGrey, and two clinical trial registries were searched (until March 30, 2022) using descriptors for subconcussive head impacts, biomarkers, and contact sports. Included studies were assessed for risk of bias and quality. RESULTS: Seventy-nine research publications were included in the review. Forty-nine studies assessed the acute effects, 23 semi-acute and 26 long-term effects of RSHI exposure. The most studied sports were American football, boxing, and soccer, and the most investigated markers were (in descending order): S100 calcium-binding protein beta (S100B), tau, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), phosphorylated tau (p-tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and hormones. High or moderate bias was found in most studies, and marker-specific conclusions were subject to heterogeneous and limited evidence. Although the evidence is weak, some biofluid markers-such as NfL-appeared to show promise. More markedly, S100B was found to be problematic when evaluating the effects of RSHI in sport. CONCLUSION: Considering the limitations of the evidence base revealed by this first review dedicated to systematically scoping the evidence of biofluid marker levels following RSHI exposure, the field is evidently still in its infancy. As a result, any recommendation and application is premature. Although some markers show promise for the assessment of brain health following RSHI exposure, future large standardized and better-controlled studies are needed to determine biofluid markers' utility.

Serum N-Glycan Profiling of Patients with Narcolepsy Type 1 Using LC-MS/MS.

The neurological condition known as narcolepsy type 1 (NT1) is an uncommon condition marked by extreme daytime sleepiness, cataplexy, sleep paralysis, hallucinations, disrupted nocturnal sleep, and low or undetectable levels of orexin in the CSF fluid. NT1 has been hypothesized to be an immunological disorder; its treatment is currently only symptomatic, and misdiagnosis is not uncommon. This study compares the N-glycome of NT1 patients with healthy controls in search of potential glycan biomarkers using LC-MS/MS. A total of 121 candidate N-glycans were identified, 55 of which were isomeric N-glycan structures and 65 were not. Seventeen N-glycan biomarker candidates showed significant differences between the NT1 and control cohorts. All of the candidate glycan biomarkers were isomeric except HexNAc6Hex7Fuc0NeuAc1 (6701) and HexNAc6Hex7Fuc1NeuAc2 (6712). Therefore, with isomeric and nonisomeric structures, a total of 20 candidate N-glycan biomarkers are reported in this study, and interestingly, all are either sialylated or sialylated-fucosylated and upregulated in NT1 relative to the control. The distribution levels of all the identified N-glycans show that the sialylated glycan type is the most abundant in NT1 and is majorly disialylated, although the trisialylated subtype is three-fold higher in NT1 compared to the healthy control. The first isomers of HexNAc5Hex6Fuc0NeuAc3 (5603), HexNAc6Hex7Fuc0NeuAc2 (6702), and HexNAc6Hex7Fuc1NeuAc4 (6714) expressed a high level of fold changes (FC) of 1.62, 2.19, and 2.98, respectively. These results suggest a different N-glycome profile of NT1 and a relationship between sialylated glycan isomers in NT1 disease development or progression. The revelation of N-glycan expression alterations in this study may improve NT1 diagnostic methods, understanding of NT1 pathology, and the development of new targeted therapeutics.

Corrigendum: Time-Trends in Air Pollution Impact on Health in Italy, 1990-2019: An Analysis from the Global Burden of Disease Study 2019.

[This corrects the article DOI: 10.3389/ijph.2023.1605959.].