Neurology最新文献

{"title":"Clinical Reasoning: Episodes of Uncontrollable Crying in a 52-Year-Old Man With a Sphenopetroclival Tumor.","authors":"Zeynep Özdemir,Stjepana Kovac,Walter Stummer,Michael Müther","doi":"10.1212/wnl.0000000000213847","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213847","url":null,"abstract":"A 52-year-old man presented with progressive gait disturbances. MRI demonstrated a large extra-axial tumor in the cerebellopontine angle compressing the brainstem and resulting in hydrocephalus. While taking the patient's history, episodes of uncontrollable crying with sudden onset occurred multiple times. In this case report, we present and discuss the differential diagnoses of episodes of uncontrollable crying without emotional affect in adults and the possible underlying etiology.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"46 1","pages":"e213847"},"PeriodicalIF":9.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Better Communication With the Public: Understanding Science Phobia and Mistrust as Neurobiological Phenomena.","authors":"Nina F Schor","doi":"10.1212/wnl.0000000000213862","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213862","url":null,"abstract":"Much has been written recently about science mistrust and illiteracy and consequent phobia of recommendations and interventions that have grown out of that science. Both reinforcing and reversing these phenomena depend on strategies aimed at brain networks that generate them. The neurogenesis of specific phobias involves a network that includes the amygdala and the hypothalamus and their connection through the stria terminalis. Decreased GABAergic inhibition of this circuit results in limbic activation and induction of fear pathways. The neurogenesis of mistrust involves suppression of a network that includes the central amygdala and the shell of the nucleus accumbens, both of which are rich in oxytocin receptors and yield dopaminergic output. Oxytocin signaling mediates trust, whereas, at least in men, dihydrotestosterone signaling mediates mistrust. The possibility of involvement of these limbic circuits in both science phobia and mistrust may underlie the high efficacy of emotionally focused communication in reinforcing them. Yet, recent efforts to reverse science phobia and mistrust have more often involved intellectually focused communication. Assuming limbic network origins of science phobia and mistrust, this commentary presents and discusses the use of emotionally focused communication and explicit, public identification of manipulative techniques and innuendo to influence the prevalence of these phenomena.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"271 1","pages":"e213862"},"PeriodicalIF":9.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"General vs Nongeneral Anesthesia for Endovascular Thrombectomy in Patients With Large Core Strokes: A Prespecified Secondary Analysis of SELECT2 Trial.","authors":"Amrou Sarraj,Spiros Blackburn,Michael G Abraham,Muhammad S Hussain,Santiago Ortega-Gutierrez,Michael Chen,Scott E Kasner,Leonid Churilov,Clark W Sitton,Deep K Pujara,Sophia Sundararajan,Yin C Hu,Nabeel A Herial,Ronald F Budzik,William J Hicks,Nirav Vora,Juan F Arenillas,Mercedes De Lara Alfonso,Maria E Ramos Araque,Jenny P Tsai,Mohammed A Abdulrazzak,Osman Kozak,Bernard Yan,Peter J Mitchell,Dennis J Cordato,Nathan W Manning,Andrew Cheung,Ricardo A Hanel,Amin N Aghaebrahim,Teddy Y Wu,Pere Cardona Portela,Andres J Paipa Merchán,Chirag D Gandhi,Fawaz Al-Mufti,Edgar A Samaniego,Laith Maali,Abed Qureshi,Colleen G Lechtenberg,Sabreena Slavin,Lee Rosterman,Daniel Gibson,Adam N Wallace,Daniel Sahlein,Natalia Pérez de la Ossa,Maria Hernández Pérez,Joanna D Schaafsma,Jordi Blasco,Arturo Renú,Navdeep Sangha,Steven Warach,Timothy J Kleinig,Michael Mullen,Lucas Elijovich,Faris Shaker,Faisal K Al-Shaibi,Hannah Johns,Kelsey R Duncan,Amanda Opaskar,Marc J Popovic,Michael Altose,Abhishek Ray,Wei Xiong,Jeffrey Sunshine,Michael DeGeorgia,Thanh N Nguyen,Johanna T Fifi,Stavropoula Tjoumakaris,Pascal Jabbour,Vitor Mendes Pereira,Maarten G Lansberg,Greg W Albers,Cathy Sila,Nicholas Bambakidis,Stephen Davis,Lawrence Wechsler,Michael D Hill,James C Grotta,Marc Ribo,Ameer E Hassan,Bruce C Campbell,","doi":"10.1212/wnl.0000000000213819","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213819","url":null,"abstract":"BACKGROUND AND OBJECTIVESThe association of anesthesia approach during endovascular thrombectomy (EVT) with clinical outcomes in large strokes is unexplored. We aimed to evaluate whether general anesthesia (GA), compared with non-GA, was associated with better functional outcomes in the SELECT2 trial.METHODSIn a prespecified secondary analysis of the SELECT2 trial that enrolled patients with large strokes on noncontrast CT (Alberta Stroke Program Early CT Score [ASPECTS] 3-5), CT perfusion/MRI (core volume ≥50 mL), or both, functional outcomes were compared in EVT-treated patients who received GA or non-GA and whether this association was modified by stroke severity (NIH Stroke Scale score), ischemic injury estimates, and collateral status was evaluated. The primary outcome was 90-day functional status (ordinal modified Rankin Scale [mRS]). Secondary outcomes were functional independence (mRS scores 0-2), independent ambulation (mRS scores 0-3), complete dependence or death (mRS scores 5-6), and mortality.RESULTSOf 178 EVT patients (median [interquartile range] age 66 [58-75] years, stroke severity 19 [15-23], CT-ASPECTS 4 [3-5], and core volume 101.5 [70-138] mL, 71 women [39.9%]), 104 (58%) received GA. Time from randomization to arterial puncture was longer with GA (40 [23-59] minutes) vs non-GA (27 [18-47] minutes), but procedural duration (GA: 57 [31.5-77] minutes vs non-GA: 49.5 [30-71] minutes) was similar. Successful reperfusion (modified treatment in cerebral infarction [mTICI] score 2b-3) rates were similar (GA 81 (78%) vs non-GA 62 (84%), adjusted relative risk [aRR] 0.91, 95% CI 0.79-1.06). In addition, mRS distribution did not differ between GA and non-GA groups (adjusted generalized odds ratio 1.21, 95% CI 0.86-1.70), as well as independent ambulation (GA: 41% vs non-GA: 34%, aRR 1.22, 95% CI 0.86-1.74) and functional independence (GA: 22% vs non-GA: 18%, aRR 1.32, 95% CI 0.75-2.35). Stroke severity, ASPECTS, ischemic core volume, or collaterals did not modify the association between anesthesia and functional outcome (all p-interaction >0.05). Patients experienced systolic blood pressure (SBP) variability ≥40 mm Hg and minimum intraprocedural SBP (<100 mm Hg) more frequently with GA, but this did not modify GA association with functional outcomes (p-interaction = 0.77 and 0.89, respectively).DISCUSSIONIn patients with large core strokes randomized in SELECT2, EVT outcomes did not differ significantly based on anesthesia approach (GA or non-GA) without heterogeneity across stroke severity and size. While GA was associated with higher SBP variability and lower minimum SBP, this did not modify GA association with functional outcomes. While allocation to anesthesia approach was nonrandomized, our findings suggest that optimizing institutional protocols for preferred anesthesia technique, whether GA or non-GA, may enhance EVT procedural outcomes.TRIAL REGISTRATION INFORMATIONClinicalTrials.gov ID: NCT03876457.CLASSIFICATION OF EVIDENCETh","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"18 1","pages":"e213819"},"PeriodicalIF":9.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Diagnosis of Intracerebral Hemorrhage in Patients With Acute Stroke by Measuring Prehospital GFAP Levels on a Point-of-Care Device (DETECT).","authors":"Love-Preet Kalra,Sabina Zylyftari,Kristaps Blums,Stephan Barthelmes,Hannsjoerg Baum,Stephan Meckel,Andreas Heilgeist,Sebastian Luger,Christian Foerch","doi":"10.1212/wnl.0000000000213823","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213823","url":null,"abstract":"BACKGROUND AND OBJECTIVESThe rapid identification of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke is decisive for prehospital triage and initiation of targeted therapies. Glial fibrillary acidic protein (GFAP) is a highly promising blood-biomarker indicating ICH. In this study, we investigated the potential of a new GFAP test run on a point-of-care platform for distinguishing ICH from ischemic stroke (IS) and stroke mimics (SM) in the prehospital phase.METHODSThis prospective diagnostic accuracy study was conducted at the RKH Klinikum Ludwigsburg, a tertiary care hospital in Baden-Württemberg, Germany. Patients with symptoms of acute stroke admitted within 6 hours of symptom onset were enrolled. Blood samples were collected in the prehospital phase. Plasma GFAP measurements were performed on the i-STAT-Alinity device (duration: 15 minutes) in-hospital. The gold standard was the final diagnosis categorized ICH, IS, or SM.RESULTSA total of 353 patients were enrolled (mean age 74.6 ± 13.4 years; 46.7% female). GFAP concentrations were elevated in patients with ICH (n = 76; median 208 pg/mL [interquartile range 60-5,907]) compared with IS (n = 258; 30 pg/mL [29-51]) and SM (n = 19; 48 pg/mL [29-97]; p < 0.001). The optimal GFAP cutoff point to differentiate ICH from IS and SM was 55 pg/mL (area under the curve of 0.880, 95% CI 0.834-0.925, p < 0.001). IS and SM GFAP levels slightly increased in parallel with increasing age. Hence, different GFAP cutoff points were determined to identify ICH across 3 age groups with moderate to high positive predictive values (PPVs) (90.0%-95.5%; minimum lower CI 55.0%, maximum upper CI 99.3%) (sensitivity values 56.3%-72.4%, specificity values 98.9%-99.0% and negative predictive values [NPVs] 87.5%-92.7%). Vice versa, in patients with a moderate to severe neurologic deficit (NIH Stroke Scale >6), GFAP values <30 pg/mL ruled out ICH with a NPV of 100.0%.DISCUSSIONLaboratory GFAP measurements on a point-of-care platform in blood samples collected from patients with symptoms of acute stroke in the prehospital phase can help to identify ICH with moderate to high PPV. Following confirmation in larger independent cohorts using optimized eligibility criteria and validated age-specific cutoff values, GFAP testing could facilitate optimized triage and the initiation of blood pressure-lowering therapy and anticoagulation reversal in earlier time frames.CLASSIFICATION OF EVIDENCEThis study provides Class II evidence that elevated plasma GFAP levels within 6 hours of symptom onset accurately distinguish patients with ICH from IS and SM.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"48 1","pages":"e213823"},"PeriodicalIF":9.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic Spectrum in Individuals With Pathogenic GABRG2 Loss- and Gain-of-Function Variants.","authors":"Alessandra Rossi,Susan X N Lin,Nathan L Absalom,Sebastian Ortiz-De la Rosa,Vivian W Y Liao,Nazanin A Mohammadi,Sindhu Viswanathan,Tommy Stödberg,Alberto Danieli,Paolo Bonanni,Alec Aeby,Alessandro Orsini,Alice Bonuccelli,Andrea Rüegger,Beatriz G Giraldez,Bertrand Isidor,Burkhard Stüve,Carla Marini,Elisabetta Cesaroni,Christina D Fenger,Christophe Philippe,Colombine Meunier,Damien Lederer,Stéphanie Moortgat,Egidio Spinelli,Elisa Fallica,Fiona Zeiner,Matthias Bauman,Laura Licchetta,Francesca Bisulli,Francesca F Operto,Ira Benkel-Herrenbrueck,Kathleen M Gorman,Katrine M Johannesen,Konrad Platzer,Franziska Schnabel,Lieven Lagae,Mirjam Laufs,Riina Zordania,Stephen Malone,Tullio Messana,Wendy Werckx,Charlotta Jonsson,Zaid Afawi,Thomas Foiadelli,Yosra Halleb,Radka Stoeva,Mélanie Jennesson-Lyver,Gaetan Lesca,Renzo Guerrini,Samuel F Berkovic,Ingrid E Scheffer,Mary Chebib,Elena Gardella,Rikke S Møller,Guido Rubboli,Philip K Ahring","doi":"10.1212/wnl.0000000000213644","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213644","url":null,"abstract":"BACKGROUND AND OBJECTIVESVariants in the GABRG2 gene encoding the γ2 subunit of the γ-aminobutyric acid type A (GABAA) receptor are associated with a spectrum of epilepsy phenotypes. These range from simple febrile seizures to more severe conditions, including developmental and epileptic encephalopathies (DEEs). Despite previous analyses suggesting that pathogenic variants may lead to loss-of-function (LoF) receptors, a correlation between functional analysis and clinical phenotypic diversity remains elusive. We, therefore, aimed to determine why variants in the GABRG2 gene can lead to highly diverse phenotypes.METHODSWe assembled a cohort of unreported probands carrying presumed pathogenic GABRG2 variants. Electroclinical information was systematically collected, and electrophysiologic measurements were conducted for missense variants to explore potential alterations in receptor function.RESULTSWe examined 44 individuals with 35 GABRG2 variants (18 null and 17 missense). Functional assessments of the missense variants revealed that 9 caused LoF and 3 caused gain-of-function (GoF). The remaining 5 did not alter receptor function and are likely not pathogenic. Based on functional analysis and electroclinical data, 37 affected individuals were categorized into 3 groups: null LoF, missense LoF, and GoF variants. Among 19 individuals with null variants, epilepsy was diagnosed in 13, with a median onset of 14 months. The remaining 6 of 19 only had febrile seizures. Developmental delay/intellectual disability (DD/ID) was observed in 1 of 19 and psychiatric features in 4 of 18. By contrast, all 12 individuals with missense LoF variants suffered from epilepsy with a median onset of 15 months. Most common epilepsy diagnoses were febrile seizures plus in 4 of 12 and DEE in 4 of 12. DD/ID affected 9 of 12, and psychiatric features were diagnosed in 8 of 12. Statistical comparisons revealed that null variants were associated with a milder phenotype than missense LoF variants. Finally, 5 of 6 individuals with GoF variants had DEE characterized by early infancy onset at 2 months and severe/profound DD/ID. The sixth individual exhibited mild DD/ID and hypotonia without seizures.DISCUSSIONOur findings indicate that the severity of disease associated with pathogenic GABRG2 variants depends on the functional consequences of the variants. Null variants are associated with a mild phenotype and missense LoF variants with an intermediate phenotype while GoF variants can lead to severe phenotypes.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"10 1","pages":"e213644"},"PeriodicalIF":9.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GFAP for Early ICH Detection: A New Prehospital Tool Emerges?","authors":"Lauren Mamer,Frederick K Korley","doi":"10.1212/wnl.0000000000213910","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213910","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"27 1","pages":"e213910"},"PeriodicalIF":9.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracranial Nonstenosing Atherosclerotic Plaques Assessed With Vessel Wall MRI in Patients With Embolic Stroke of Undetermined Source.","authors":"Federico Mazzacane,Beatrice Del Bello,Elisa Rognone,Carlo Asteggiano,Federica Ferrari,Alessandra Persico,Alfredo Costa,Roberto De Icco,Andrea Morotti,Anna Pichiecchio,Anna Cavallini","doi":"10.1212/wnl.0000000000213833","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213833","url":null,"abstract":"BACKGROUND AND OBJECTIVESArtery-to-artery embolization from vulnerable intracranial nonstenosing atherosclerotic plaques (vNSPs) has been proposed as a major contributor to embolic stroke of undetermined source (ESUS). Vessel wall MRI (VWMRI) offers the potential to identify culprit vNSPs, yet prospective studies in ESUS populations are lacking. This study aimed to assess the role of vNSPs in single-territory ESUS and to evaluate the utility of intracranial VWMRI in the diagnostic workup.METHODSConsecutive patients admitted to the Stroke Unit of the IRCCS Mondino Foundation (Pavia, Italy) with a confirmed ESUS diagnosis after a complete etiologic workup were prospectively enrolled in the study. Patients with multiterritorial ischemic lesions, complicated aortic arch atherosclerosis, or a probable patent foramen ovale-associated stroke were excluded. Intracranial VWMRI at 3-T was performed within 1 month of the index event. Atherosclerotic lesions were considered culprit if demonstrating postcontrast enhancement on T1-weighted images and a location consistent with ischemic lesions' distribution. Quantitative radiologic features of vNSPs were also analyzed.RESULTSA total of 80 patients (mean age 65.6 years, 34 [42.5%] women) were included. VWMRI identified a potentially culprit vNSP in 23 of 80 patients (28.8%, 95% CI 20-39.5). Patients with symptomatic vNSPs were older (72.7 vs 62.8 years, p = 0.002) and more frequently current (43.5 vs 35.1%) or former (30.4 vs 8.8%) smokers (p = 0.014). In a multivariable logistic regression model including major risk factors of intracranial atherosclerosis (age, smoking, hypertension, diabetes, and dyslipidemia), both age (adjusted odds ratio [aOR] 1.12, 95% CI 1.05-1.22, p = 0.002) and smoking status (active smokers: aOR 7.99, 95% CI 1.81-47.8, p = 0.011; former smokers: aOR 8.79, 95% CI 1.73-55.0, p = 0.012) were significantly associated with symptomatic vNSP.DISCUSSIONIntracranial vNSPs may represent a significant underlying cause of single-territory ESUS, and VWMRI could provide an added value in the diagnostic workup of these patients. Older age and smoking exposure were found to be independently associated with the presence of culprit intracranial vNSPs. Further studies are needed to confirm our findings because of the relatively small and monocentric cohort.CLASSIFICATION OF EVIDENCEThis study provides Class IV evidence that VWMRI improves the identification of culprit vNSPs in patients with ESUS.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"652 1","pages":"e213833"},"PeriodicalIF":9.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Principles for Novel Neurologic Therapeutics: An AAN Position Statement.","authors":"Larry B Goldstein,Jonathan R Crowe,Anindita Deb,Justin T Jordan,Jonathan D Santoro,James J Sejvar,Madeline Turbes,Robert E Shapiro","doi":"10.1212/wnl.0000000000213850","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213850","url":null,"abstract":"This statement provides general principles of the American Academy of Neurology's (AAN) approach when invited to provide guidance to policymakers on a variety of types of therapies that may have neurologic treatment benefits, but for which available evidence is limited or for which there is no US Food and Drug Administration-approved indication. In these instances, the AAN recommends an approach in which the patient and neurologist carefully review all available evidence and discuss the potential risks and benefits of the therapy, including when patients are contemplating asserting their right to try.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"55 1","pages":"e213850"},"PeriodicalIF":9.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-Sectional and Longitudinal Associations of Neighborhood Disadvantage With Fluid Biomarkers of Neuroinflammation and Neurodegeneration.","authors":"Marissa A Gogniat,Omair A Khan,Brina Ratangee,Corey J Bolton,Panpan Zhang,Dandan Liu,Kimberly R Pechman,Alexis Yates,Leslie S Gaynor,James Eaton,Amalia Peterson,Katherine A Gifford,Timothy J Hohman,Kaj Blennow,Henrik Zetterberg,Angela L Jefferson","doi":"10.1212/wnl.0000000000213770","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213770","url":null,"abstract":"BACKGROUND AND OBJECTIVESLiving in a socioeconomically disadvantaged neighborhood has an adverse impact on health outcomes, including increased risk of Alzheimer disease (AD). The biological mechanisms underlying this risk are poorly understood. We sought to examine how neighborhood disadvantage relates to core AD pathology, neurodegeneration, and inflammatory biomarkers in community-dwelling older adults cross-sectionally and over time.METHODSParticipants included older adults from the Vanderbilt Memory and Aging Project who underwent fasting blood and CSF acquisition serially over a 9-year follow-up period (mean follow-up = 6.4 years [blood] and 4.0 years [CSF]). Area Deprivation Index (ADI), representing neighborhood disadvantage, was quantified at baseline using 17 components (e.g., housing, income, education, and household characteristics), with higher values indicating greater disadvantage. Ordinary least-squares regressions cross-sectionally related ADI to plasma and CSF inflammatory biomarkers adjusting for age, sex, race/ethnicity, education, modified Framingham Stroke Risk Profile score, APOE ε4 status, and cognitive status. Linear mixed-effects regression models related ADI to longitudinal biomarkers with identical covariates plus follow-up time. Outcomes included CSF chitinase-3-like protein 1 (YKL-40), CSF soluble-triggering receptor expressed on myeloid cells 2, CSF amyloid-β42 (Aβ42), CSF Aβ40/Aβ42 ratio, CSF tau, CSF phosphorylated tau (ptau), plasma high-sensitivity C-reactive protein (CRP), and plasma and CSF neurofilament light chain.RESULTSParticipants (n = 334; 73 ± 8 years old, 59% male, 86% White, non-Hispanic) on average were from relatively less disadvantaged neighborhoods (ADI national decile = 33 ± 25, range = 1-98). Greater neighborhood disadvantage at study entry was cross-sectionally associated with elevated CSF YKL-40 (β = 0.7, p = 0.003) and tau (β = 1.8, p = 0.04) after excluding outliers. Greater neighborhood disadvantage at study entry related to faster longitudinal increases in plasma CRP (β = 0.005, p = 0.03).DISCUSSIONGreater neighborhood disadvantage was associated with elevated inflammatory and AD CSF biomarkers cross-sectionally and longitudinal increases in a nonspecific inflammatory blood biomarker. Findings suggest that neighborhood disadvantage confers risk of systemic inflammation and AD pathology, providing a possible sociobiological mechanism underlying health disparities in aging adults; however, results were limited by use of ADI at study entry.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"17 1","pages":"e213770"},"PeriodicalIF":9.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Sociobiological Mechanisms of Diseases: A Call to Promote Equity in Brain Health.","authors":"Salvatore Mazzeo,Maria Salsone","doi":"10.1212/wnl.0000000000213922","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213922","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"21 1","pages":"e213922"},"PeriodicalIF":9.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}