Brain communications最新文献

{"title":"The relationship between leisure time physical activity patterns, Alzheimer's disease markers and cognition.","authors":"Sarah-Naomi James, Carole H Sudre, Josephine Barnes, David M Cash, Yu-Jie Chiou, William Coath, Ashvini Keshavan, Kirsty Lu, Ian Malone, Heidi Murray-Smith, Jennifer M Nicholas, Michele Orini, Thomas Parker, Pamela Almeida-Meza, Nick C Fox, Marcus Richards, Jonathan M Schott","doi":"10.1093/braincomms/fcae431","DOIUrl":"10.1093/braincomms/fcae431","url":null,"abstract":"<p><p>We assessed the association between leisure time physical activity patterns across 30 years of adulthood with a range of <i>in vivo</i> Alzheimer's disease-related neurodegenerative markers and cognition, and their interplay, at age 70. Participants from the 1946 British birth cohort study prospectively reported leisure time physical activity five times between ages 36 and 69 and were dichotomized into (i) not active (no participation/month) and (ii) active (participated once or more/month) and further derived into: (0) never active (not active); (1) active before 50's only (≤43 years); (2) active from 50's onwards only (≥53 years); (3) always active (active throughout). Participants underwent 18F-florbetapir Aβ and magnetic resonance imaging at age 70. Regression analyses were conducted to assess the direct and the moderating relationship between leisure time physical activity metrics, Alzheimer's disease-related neurodegeneration markers (including Aβ status, hippocampal and whole-brain volume, and cortical thickness in Alzheimer's disease signature regions) and cognition. All models were adjusted for childhood cognition, education and childhood socioeconomic position, and examined by sex. Findings drawn from 468 participants (49% female) demonstrated a direct association between being active before 50 years old (≤43 years) and throughout life (up to age 69 years), with larger hippocampal volume at age 70 (<i>P</i> < 0.05). There was little evidence that leisure time physical activity had direct effects on other brain health measures (all <i>P</i> > 0.05). However, leisure time physical activity patterns modified and attenuated the association between poorer cognitive functioning at age 70 and a range of Alzheimer's disease-related neurodegenerative markers (Aβ status; hippocampal and whole-brain volume; cortical thickness in Alzheimer's disease regions) (all <i>P</i> < 0.05). We found suggestive evidence that women with early markers of Alzheimer's disease-related neurodegeneration were most sensitive to leisure time physical activity patterns: a lifetime of inactivity in women exacerbated the manifestation of early Alzheimer's disease markers (Aβ and cortical thickness-related cognition), yet, if women were active across life or early in life, it mostly buffered these negative relationships. Engagement in leisure time physical activity in the life course is associated with better cognitive functioning at age 70, even in those with early markers of Alzheimer's disease. If causal, this is likely via multiple pathways, potentially through the preservation of hippocampal volume, as well as via cognitive resilience pathways delaying cognitive manifestations of early markers of Alzheimer's disease, particularly in women. Our findings warrant further research to shed light on the mechanisms of physical activity as a potential disease-modifying intervention of brain health and cognitive resilience.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcae431"},"PeriodicalIF":4.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unmasking paramagnetic rim multiple sclerosis lesions: the advantages of quantitative susceptibility mapping over phase imaging.","authors":"Àlex Rovira, Deborah Pareto","doi":"10.1093/braincomms/fcaf037","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf037","url":null,"abstract":"<p><p>This scientific commentary refers to 'Quantitative susceptibility mapping is more sensitive and specific than phase imaging in detecting chronic active multiple sclerosis lesion rims: pathological validation', by Gillen <i>et al</i>. (https://doi.org/10.1093/braincomms/fcaf011).</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf037"},"PeriodicalIF":4.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The challenge of long-term stroke outcome prediction and how statistical correlates do not imply predictive value.","authors":"Christoph Sperber, Laura Gallucci, Marcel Arnold, Roza M Umarova","doi":"10.1093/braincomms/fcaf003","DOIUrl":"10.1093/braincomms/fcaf003","url":null,"abstract":"<p><p>Personalized prediction of stroke outcome using lesion imaging markers is still too imprecise to make a breakthrough in clinical practice. We performed a combined prediction and brain mapping study on topographic and connectomic lesion imaging data to evaluate (i) the relationship between lesion-deficit associations and their predictive value and (ii) the influence of time since stroke. In patients with first-ever ischaemic stroke, we first applied high-dimensional machine learning models on lesion topographies or structural disconnection data to model stroke severity (National Institutes of Health Stroke Scale 24 h/3 months) and functional outcome (modified Rankin Scale 3 months) in cross-validation. Second, we mapped the topographic and connectomic lesion impact on both clinical measures. We retrospectively included 685 patients [age 67.4 ± 15.1, National Institutes of Health Stroke Scale 24 h median(IQR) = 3(1; 6), modified Rankin Scale 3 months = 1(0; 2), National Institutes of Health Stroke Scale 3 months = 0(0; 2)]. <i>Predictions</i> for acute stroke severity (National Institutes of Health Stroke Scale 24 h) were better with topographic lesion imaging (<i>R</i>² = 0.41) than with disconnection data (<i>R</i>² = 0.29, <i>P</i> = 0.0015), whereas predictions at 3 months (National Institutes of Health Stroke Scale/modified Rankin Scale) were generally close to chance level. In the analysis of lesion-deficit <i>associations</i>, the correlates of more severe acute stroke (National Institutes of Health Stroke Scale 24 h > 4) and poor functional outcome (modified Rankin Scale 3 months ≥ 2) were left-lateralized. The lesion location impact of both variables corresponded in right-hemisphere stroke with peaks in primary motor regions, but it markedly differed in left-hemisphere stroke. Topographic and disconnection lesion features predict <i>acute</i> stroke severity better than the <i>3-months</i> outcome. This suggests a likely higher impact of lesion-independent factors in the longer term and highlights challenges in the prediction of global functional outcome. Prediction and brain mapping diverge, and the existence of statistically significant associations-as here for 3-months outcomes-does not imply predictive value. Routine neurological scores better capture left- than right-hemispheric lesions, further complicating the challenge of outcome prediction.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf003"},"PeriodicalIF":4.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal relationships between hippocampal volumetric traits and the risk of Alzheimer's disease: a Mendelian randomization study.","authors":"Lining Guo, Yayuan Chen, Zuhao Sun, Jiaxuan Zhao, Jia Yao, Zhihui Zhang, Minghuan Lei, Ying Zhai, Jinglei Xu, Yurong Jiang, Ying Wang, Hui Xue, Mengge Liu, Feng Liu","doi":"10.1093/braincomms/fcaf030","DOIUrl":"10.1093/braincomms/fcaf030","url":null,"abstract":"<p><p>Alzheimer's disease, a common and progressive neurodegenerative disorder, is associated with alterations in hippocampal volume, as revealed by neuroimaging research. However, the causal links between the volumes of the hippocampus and its subfield structures with Alzheimer's disease remain unknown. A genetic correlation analysis using linkage disequilibrium score regression was conducted to identify hippocampal volumetric traits linked to Alzheimer's disease. Following this, to examine the causal links between Alzheimer's disease and hippocampal volumetric traits, we applied a two-sample Mendelian randomization approach, utilizing a bidirectional framework. Seven hippocampal volumetric traits were found as genetically correlated with Alzheimer's disease in the genetic correlation analysis and were then included in the Mendelian randomization analyses. Inverse variance weighted Mendelian randomization analyses revealed that increased volumes in the left whole hippocampus, left hippocampal body, right presubiculum head and right cornu ammonis 1 head were causally related to higher risks of Alzheimer's disease. Conversely, a higher risk of Alzheimer's disease was causally associated with decreased volumes of the left hippocampal body and left whole hippocampus. These results were validated through other Mendelian randomization approaches and sensitivity analysis. Our findings uncover bidirectional causal relationships between Alzheimer's disease and hippocampal volumetric traits, suggesting not only the potential significance of these traits in predicting Alzheimer's disease but also the reciprocal influence of Alzheimer's disease on hippocampal volumes.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf030"},"PeriodicalIF":4.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating conversion from mild cognitive impairment to Alzheimer's disease with structural MRI: a machine learning study.","authors":"Daniela Vecchio, Federica Piras, Federica Natalizi, Nerisa Banaj, Clelia Pellicano, Fabrizio Piras","doi":"10.1093/braincomms/fcaf027","DOIUrl":"10.1093/braincomms/fcaf027","url":null,"abstract":"<p><p>Alzheimer's disease is a disabling neurodegenerative disorder for which no effective treatment currently exists. To predict the diagnosis of Alzheimer's disease could be crucial for patients' outcome, but current Alzheimer's disease biomarkers are invasive, time consuming or expensive. Thus, developing MRI-based computational methods for Alzheimer's disease early diagnosis would be essential to narrow down the phenotypic measures predictive of cognitive decline. Amnestic mild cognitive impairment (aMCI) is associated with higher risk for Alzheimer's disease, and here, we aimed to identify MRI-based quantitative rules to predict aMCI to possible Alzheimer's disease conversion, applying different machine learning algorithms sequentially. At baseline, T1-weighted brain images were collected for 104 aMCI patients and processed to obtain 146 volumetric measures of cerebral grey matter regions [regions of interest (ROIs)]. One year later, patients were classified as converters (aMCI-c = 32) or non-converters, i.e. clinically and neuropsychologically stable (aMCI-s = 72) based on cognitive performance. Feature selection was performed by random forest (RF), and the identified seven ROIs volumetric data were used to implement support vector machine (SVM) and decision tree (DT) classification algorithms. Both SVM and DT reached an average accuracy of 86% in identifying aMCI-c and aMCI-s. DT found a critical threshold volume of the right entorhinal cortex (EC-r) as the first feature for differentiating aMCI-c/aMCI-s. Almost all aMCI-c had an EC-r volume <1286 mm³, while more than half of the aMCI-s patients had a volume above the identified threshold for this structure. Other key regions for the classification between aMCI-c/aMCI-s were the left lateral occipital (LOC-l), the middle temporal gyrus and the temporal pole cortices. Our study reinforces previous evidence suggesting that the morphometry of the EC-r and LOC-l best predicts aMCI to Alzheimer's disease conversion. Further investigations are needed prior to deeming our findings as a broadly applicable predictive framework. However, here, a first indication was derived for volumetric thresholds that, being easy to obtain, may assist in early identification of Alzheimer's disease in clinical practice, thus contributing to establishing MRI as a useful non-invasive prognostic instrument for dementia onset.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf027"},"PeriodicalIF":4.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early subacute frontal callosal microstructure and language outcomes after stroke.","authors":"Veronika Vadinova, Sonia L E Brownsett, Kimberley L Garden, Tracy Roxbury, Katherine O'Brien, David A Copland, Katie L McMahon, Aleksi J Sihvonen","doi":"10.1093/braincomms/fcae370","DOIUrl":"10.1093/braincomms/fcae370","url":null,"abstract":"<p><p>The integrity of the frontal segment of the corpus callosum, forceps minor, is particularly susceptible to age-related degradation and has been associated with cognitive outcomes in both healthy and pathological ageing. The predictive relevance of forceps minor integrity in relation to cognitive outcomes following a stroke remains unexplored. Our goal was to evaluate whether the heterogeneity of forceps minor integrity, assessed early after stroke onset (2-6 weeks), contributes to explaining variance in longitudinal outcomes in post-stroke aphasia. Both word- and sentence-level tasks were employed to assess language comprehension and language production skills in individuals with first-ever left-hemisphere stroke during the early subacute and chronic phases of recovery (<i>n</i> = 25). Structural and diffusion neuroimaging data from the early subacute phase were used to quantify stroke lesion load and bilateral forceps minor radial diffusivity. Multiple linear regression models examined whether early subacute radial diffusivity within the forceps minor, along with other factors (stroke lesion load, age, sex and education), explained variance in early subacute performance and longitudinal recovery (i.e. change in behavioural performance). Increased early subacute radial diffusivity in the forceps minor was associated with poor early subacute comprehension (<i>t</i> = -2.36, <i>P</i> = 0.02) but not production (<i>P</i> = 0.35) when controlling for stroke lesion load, age, sex and education. When considering longitudinal recovery, early subacute radial diffusivity in the forceps minor was not linked to changes in performance in either comprehension (<i>P</i> = 0.11) or production (<i>P</i> = 0.36) under the same control variables. The examination of various language components and processes led to novel insights: (i) language comprehension may be more susceptible to white matter brain health than language production and (ii) the influence of white matter brain health is reflected in early comprehension performance rather than longitudinal changes in comprehension. These results suggest that evaluating baseline callosal integrity is a valuable approach for assessing the risk of impaired language comprehension post-stroke, while also underscoring the importance of nuanced analyses of behavioural outcomes to enhance our understanding of the clinical applicability of baseline brain health measures.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcae370"},"PeriodicalIF":4.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidimensional structural analyses revealed a correlation between thalamic atrophy and white matter degeneration in idiopathic dystonia.","authors":"Jinping Xu, Qinxiu Cheng, Yue Zhang, Yuhan Luo, Linchang Zhong, Huiming Liu, Haoran Zhang, Zhengkun Yang, Jiana Zhang, Zilin Ou, Zhicong Yan, Kangqiang Peng, Gang Liu","doi":"10.1093/braincomms/fcaf026","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf026","url":null,"abstract":"<p><p>Although aberrant changes in grey and white matter are core features of idiopathic dystonia, few studies have explored the correlation between grey and white matter changes in this disease. This study aimed to investigate the coupling correlation between morphological and microstructural alterations in patients with idiopathic dystonia. Structural T1 imaging and diffusion tensor imaging were performed on a relatively large cohort of patients. Multidimensional structural analyses, including voxel-based analyses, voxel-based morphology, fixel-based analyses and surface-based morphometry, were performed to explore these structural alterations. Probabilistic tractography and correlation analyses were employed to examine these relationships. A total of 147 patients with idiopathic dystonia and 137 healthy controls were recruited in this study. There were no significant differences in the cortical morphometry between patients with idiopathic dystonia and healthy controls using voxel- and surface-based morphometry. However, the grey matter volume of the bilateral thalamus, fractional anisotropy in the right anterior corona radiata, right retrolenticular part of the internal capsule and right posterior corona radiata, and the fibre density and cross-section combined in the fibre tract connecting the left ventral posterolateral thalamic nucleus and left area 5 m, were significantly decreased in patients with idiopathic dystonia compared with those in healthy controls. Furthermore, the reduced grey matter volume in the right thalamus not only correlated with the disease duration but also with the reduced fractional anisotropy in the right posterior corona radiata and decreased the fibre density and cross-section combined in the fibre tract connecting the left ventral posterolateral thalamic nucleus and the left area 5 m in patients with idiopathic dystonia. These findings suggest that the thalamus is structurally impaired in idiopathic dystonia and that microstructural disruption in thalamocortical projections occurs secondary to thalamic atrophy.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf026"},"PeriodicalIF":4.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult phenotypes of genetic developmental and epileptic encephalopathies.","authors":"Angeliki Vakrinou, Susanna Pagni, James D Mills, Lisa M Clayton, Simona Balestrini, Sanjay M Sisodiya","doi":"10.1093/braincomms/fcaf028","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf028","url":null,"abstract":"<p><p>Developmental and epileptic encephalopathies constitute a group of severe epilepsies, with seizure onset typically occurring in infancy or childhood, and diverse clinical manifestations, including neurodevelopmental deficits and multimorbidities. Many have genetic aetiologies, identified in up to 50% of individuals. Whilst classically considered paediatric disorders, most are compatible with survival into adulthood, but their adult phenotypes remain inadequately understood. This cross-sectional study presents detailed phenotypes of 129 adults (age range 17-71 years), with genetic developmental and epileptic encephalopathies involving causal variants in 42 genes. We describe diverse disease aspects, and we sought genetic insights from the age-related trends of expression of the genes involved. Most developmental and epileptic encephalopathies (69.7%) are epileptic encephalopathies in adulthood, with the presence of epileptic encephalopathy correlating with worse cognitive phenotypes (<i>P</i> = 0.0007). However, phenotypic variability was observed, ranging from those with epileptic encephalopathy to seizure-free individuals with normal EEG or intermediate clinical and EEG phenotypes. This variability was found across individual genes and age-related gene expression trends, suggesting that other influential factors are likely at play. Mobility, feeding and communication impairments were common, with significant dependence on others for activities of daily living. Neurological and psychiatric comorbidities were most prevalent, along with additional systemic comorbidities observed, particularly musculoskeletal, cardiac and gastrointestinal conditions, highlighting the need for comprehensive and multisystemic monitoring. Despite an average diagnostic delay of 25.2 years, aetiology-based therapeutic interventions were feasible for 54.8% of the cohort, underscoring the critical need for genome-wide genetic testing for adults with these phenotypes. Optimizing seizure control remains necessary, but it may not be sufficient to ensure good outcomes, which may differ significantly from childhood metrics, like cognitive function and independence in daily living. Therapies addressing additional aspects beyond seizures are necessary for improving overall outcomes. Understanding the intricate relationship between molecular pathways and the age-related trends of gene expression is crucial for development of appropriate gene-specific therapies and timely intervention. Whilst prospective data are also needed to define these complexities, such studies of necessity take years to acquire: insights from adults can inform care strategies for both paediatric and adult populations now.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf028"},"PeriodicalIF":4.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI versus relapse: optimal activity monitoring for management of progressive multiple sclerosis.","authors":"Gavin Giovannoni, Suzannah Hetherington, Eddie Jones, Patricia Dominguez Castro, Himanshu Karu, Soudeh Ansari, Goeril Karlsson, Virginia de Las Heras, Carol Lines","doi":"10.1093/braincomms/fcaf010","DOIUrl":"10.1093/braincomms/fcaf010","url":null,"abstract":"<p><p>Secondary progressive multiple sclerosis is often categorized as 'active'/'non-active' based on inflammatory activity on MRI, or relapse; however, the value of MRI/relapse as indicators of disease activity in real-world and clinical trial settings merits further investigation. We separately analysed retrospective data from patients with clinically diagnosed secondary progressive multiple sclerosis in the Adelphi Real-World Disease Specific Programme (a cross-sectional survey) in multiple sclerosis (Adelphi: <i>n</i> = 2554) and the placebo group of the Phase III EXploring the efficacy and safety of siponimod in PAtients with secoNDary progressive multiple sclerosis (EXPAND) trial, [EXPAND-PBO (placebo group of the EXPAND): <i>n</i> = 546] to assess: differences between active/non-active disease in the real-world (characteristics; monitoring); the value of MRI and relapse to indicate disease activity; and the number and characteristics of non-active patients with disease activity in the clinical study. In Adelphi, 1889 patients had 'active' disease (≥1 relapse in the year before index date and/or ≥1 new lesion on most recent MRI) versus 665 with 'non-active' disease (no relapses in the previous year and no new lesions on MRI); median age was 48 versus 53 years; 73.5 versus 87.8% had moderate-to-severe disease; 75.7 versus 54.3% were taking disease-modifying treatment; 87.7 versus 58.7% had received an MRI in the past year. Most active cases (<i>n</i> = 1116; 59.1%) were identified by MRI versus 239 (12.7%) by relapse and 534 (28.3%) by MRI plus relapse. In EXPAND-PBO, 263 patients were classified 'active' (≥1 relapse in 2 years before screening and/or ≥1 gadolinium-enhancing lesion) and 270 'non-active' (no relapse in the 2 years before screening and no gadolinium-enhancing lesion[s]) at baseline; similar proportions of these groups had received disease-modifying treatment prior to placebo: 77.2 and 80.7%. Of non-active patients, 53.0% had disease activity on study; in these patients, 74.1% had disease activity identified by MRI, 8.4% by relapse, and 17.5% by MRI plus relapse. In patients classified non-active at baseline: age and percentage with Expanded Disability Status Scale score 6.0-6.5 were similar between patients with disease activity on study versus patients who remained non-active: 48 versus 52 years; 49.7 versus 56.7%, respectively. In real-world and clinical trial settings, MRI could be a better option than relapse for the identification of disease activity. However, in the real-world, fewer non-active patients had received an MRI in the last year than active patients, which is concerning given that most disease activity in EXPAND-PBO was identified via MRI. We highlight difficulties in consistently identifying disease activity and the negative implications of infrequent monitoring of non-active disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf010"},"PeriodicalIF":4.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significant oligodendrocyte progenitor and microglial cell death is a feature of remyelination following toxin-induced experimental demyelination.","authors":"Hallie Gaitsch, Peggy Assinck, Penelope Dimas, Chao Zhao, Laura Morcom, David H Rowitch, Daniel S Reich, Robin J M Franklin","doi":"10.1093/braincomms/fcae386","DOIUrl":"10.1093/braincomms/fcae386","url":null,"abstract":"<p><p>The extent to which glial cell turnover features in successful remyelination is unclear. In this study, the rat caudal cerebellar peduncle-ethidium bromide lesion model was used to profile oligodendroglial and microglial/macrophage cell death and proliferation dynamics over the course of repair. Lesioned and control tissue was co-labelled with antibody markers for cell identity, proliferation, and apoptosis (TUNEL assay), then imaged at full thickness using confocal microscopy and quantified using custom CellProfiler pipelines. Early remyelination time points were marked by an increased density of total proliferating cells, including oligodendrocyte progenitor cells. Late remyelination time points featured increased TUNEL+ oligodendrocyte progenitor cells: however, most TUNEL+ cells within remyelinating lesions were Iba1+ microglia/macrophages. These results indicate that repairing lesions are characterized by a high degree of glial cell death and suggest that monitoring cell death-related by-products might have clinical value in the setting of remyelination.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcae386"},"PeriodicalIF":4.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}