Annals of Neurology最新文献

{"title":"Annals of Neurology: Volume 100, Number 2, August 2026","authors":"","doi":"10.1002/ana.78313","DOIUrl":"https://doi.org/10.1002/ana.78313","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daily-Life, Sensor-Derived Tremor Measures Are Sensitive to Progression in Early Parkinson's Disease","authors":"Nienke A. Timmermans MSc,&nbsp;Ioan Gabriel Bucur PhD,&nbsp;Diogo C. Soriano PhD,&nbsp;Erik Post MSc,&nbsp;Hayriye Cagnan PhD,&nbsp;Sooyoon Shin PhD,&nbsp;Max A. Little PhD,&nbsp;Yordan P. Raykov PhD,&nbsp;Bastiaan R. Bloem MD, PhD,&nbsp;Rick C. Helmich MD, PhD,&nbsp;Luc J.W. Evers PhD","doi":"10.1002/ana.78236","DOIUrl":"10.1002/ana.78236","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Sensitive outcome measures are critical for evaluating the efficacy of novel treatments for Parkinson's disease (PD). In this study, we assess the sensitivity to change of sensor-derived daily-life tremor measures over 2 years in unmedicated and medicated persons with early PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used 2-year continuous wrist sensor data (median wear time: 22 hours/day) from the Personalized Parkinson Project (n = 462 medicated; n = 78 unmedicated at baseline), in combination with annual clinical evaluations of tremor severity. From the gyroscope data, we derived previously validated weekly measures for tremor time and power, which were smoothed over time using piecewise linear trend estimation. One- and 2-year standardized response means (SRMs) were computed to compare the sensitivity to change between the sensor-derived tremor measures and clinical tremor scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In unmedicated participants with tremor, sensor-derived tremor measures demonstrated a high sensitivity to progression (2-year SRMs ranged from 0.67 to 1.09), which was significantly larger than clinical tremor scores (2-year SRMs ranged from 0.21 to 0.41). In medicated participants, sensor-derived tremor time decreased (2-year SRM of −0.18), which was associated with both an increase in dopaminergic medication dose and higher disease duration. In contrast, the sensor-derived tremor power measures and clinical rest tremor scores (measured in the OFF state) increased slightly (2-year SRMs ranging from 0.11 to 0.27).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Before initiation of symptomatic treatment, sensor-derived daily-life tremor measures are substantially more sensitive to progression than clinical tremor scores, making them a promising tool to evaluate the efficacy of disease-modifying treatments in early PD. ANN NEUROL 2026;100:282–294</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"282-294"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimorbidity and Associations with Cognition and Alzheimer's Disease Biomarkers","authors":"Xiaqing Jiang PhD,&nbsp;Sid E. O'Bryant PhD,&nbsp;Robert A. Rissman PhD,&nbsp;Leigh A. Johnson PhD,&nbsp;Meredith N. Braskie PhD,&nbsp;Kristine Yaffe MD,&nbsp;the HABS-HD Study Team","doi":"10.1002/ana.78238","DOIUrl":"10.1002/ana.78238","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Multimorbidity, the coexistence of 2 or more chronic conditions, has been linked to cognitive aging and Alzheimer's disease (AD) and AD-related dementias, yet the mechanisms remain unclear. We aimed to examine the associations of multimorbidity with cognition and biomarkers across multiple mechanistic pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We cross-sectionally analyzed 3,808 dementia-free participants (mean age 64.9 ± 8.5 years, 62% female) from the Health and Aging Brain Study: Health Disparities. Multimorbidity burden was assessed using a latent construct derived from chronic conditions identified through objective measures, medical history, and self-report. A latent factor score for cognition was estimated using confirmatory factor analysis and neuropsychological tests. Using linear and logistic regression, we examined the associations of multimorbidity burden with biomarkers of AD (positron emission tomography [PET] amyloid, plasma β-amyloid 42/40, and phosphorylated tau [p-tau] measures), neurodegeneration (cortical thickness, hippocampal volume, and plasma neurofilament light and total tau), and cerebral small vessel disease (SVD) (magnetic resonance imaging white matter hyperintensities, cerebral microbleeds, and lacunes).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Greater multimorbidity burden was associated with worse cognition and biomarkers of AD (PET amyloid standardized uptake value ratios and positivity, p-tau181, and p-tau217), neurodegeneration (neurofilament light, total tau, cortical thickness, and hippocampal volume), and SVD (white matter hyperintensity volume and presence of lacune and cerebral microbleeds).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Among dementia-free individuals, higher multimorbidity burden was associated with biomarkers for greater AD pathology, neurodegeneration, and SVD. These findings support a more holistic approach to managing chronic disease burden, which has the potential to reduce overall pathophysiological burden and delay cognitive decline. ANN NEUROL 2026;100:370–379</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"370-379"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic, Prognostic Value, and Pathological Associations of Levodopa Responsiveness in Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy","authors":"Vitor Maia Arca MD,&nbsp;Justina Jurkeviciene MD,&nbsp;Patrick Cullinane MD,&nbsp;Sarah Wrigley MD,&nbsp;Jacy Bezerra Parmera MD, PhD,&nbsp;Zannatul Farin,&nbsp;Samarth Pimparkar,&nbsp;Yau Mun Lim,&nbsp;Tamas Revesz MD, FRCPath, DSc,&nbsp;Zane Jaunmuktane MD, FRCPath,&nbsp;Thomas Warner MD, FRCP, PhD,&nbsp;Eduardo de Pablo-Fernández MD, PhD","doi":"10.1002/ana.78257","DOIUrl":"10.1002/ana.78257","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to provide clinical and pathological characterization, and evaluation of the diagnostic and prognostic implications of levodopa response in Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Long-duration levodopa response in patients with pathology-confirmed PD, MSA, and PSP was collated from medical records. Associations between definite levodopa response (&gt;50% motor improvement sustained &gt;2 years) with clinical and pathological features were reported. Risk of disease milestones using multivariate Cox regression and diagnostic accuracy parameters were estimated for several measures of levodopa response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fourteen percent of 132 patients with PD (57.1% men, age at onset 60.0 ± 11.8 years) did not have a definite levodopa response associated with older age and postural-instability and gait-difficulty subtype without global or nigral pathological differences. Definite levodopa responders had 55% lower falls, 69% lower dementia risk, and 69% increased survival. Eight percent of 115 patients with MSA (55.7% men, age at onset 57.9 ± 10.4 years) showed a definite levodopa response without distinctive clinical or pathological features, and no impact on disease milestones. Two percent of 191 patients with PSP (64.4% men, age of onset 67.6 ± 7.6 years) showed a definite levodopa response associated with a PSP-parkinsonism subtype, and more frequent and severe Lewy copathology. Definite levodopa response showed excellent diagnostic accuracy (sensitivity 86.4% and specificity 95.8%) to distinguish PD from MSA and PSP. Short-duration (acute dopaminergic drug challenge) response had suboptimal diagnostic value and modest correlation with long-duration response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Levodopa response in PD, MSA, and PSP has important clinical, pathological, diagnostic, and prognostic implications. ANN NEUROL 2026;100:305–318</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"305-318"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939467","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":"Hematoma Interleukin-1 Receptor Antagonist Concentrations Predict Long-Term Outcome in Acute Human Intracerebral Hemorrhage","authors":"Adrian R. Parry-Jones,&nbsp;Blessing Nyakutsikwa,&nbsp;Michael H. Askenase,&nbsp;Matthew Gittins,&nbsp;Mary Newland,&nbsp;Siobhan Crilly,&nbsp;Paul R. Kasher,&nbsp;Yvonne Davidson,&nbsp;Federico Roncaroli,&nbsp;Stuart M. Allan,&nbsp;Lauren H. Sansing,&nbsp;Wendy Ziai,&nbsp;Daniel F. Hanley MD,&nbsp;INFLAME-ICH Investigators","doi":"10.1002/ana.78237","DOIUrl":"10.1002/ana.78237","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The interleukin (IL)-1, IL-6, and C-reactive protein (CRP) pathway is central to the immune response after intracerebral hemorrhage (ICH). We tested for associations between hematoma and plasma cytokine concentrations and patient outcomes in Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III (MISTIE III) participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Inflammation after minimally invasive evacuation of ICH (INFLAME)-ICH was a sub-study nested in MISTIE III. Daily hematoma fluid was collected from surgical patients and peripheral blood for all patients. Multiple regression models compared hematoma cytokine concentrations to the modified Rankin scale (mRS) score at 1 year. Correlations between hematoma and plasma cytokine concentrations were tested. We compared plasma cytokines in patients randomized to surgery (vs medical). Gene expression in monocyte/macrophages and neutrophils were compared in a subset of participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 89 patients were recruited (47 surgical, 42 medical). Mean hematoma IL-1 receptor antagonist (IL-1Ra) (odds ratio [OR]: 5.92; 95% confidence interval [CI]: 1.08–32.54; n = 38) and mean hematoma IL-6 (OR: 3.23; 95% CI: 1.33–7.81; n = 45) were independently associated with good outcome (mRS, 0–3) at 1 year. Higher hematoma IL-1β was associated with higher plasma CRP (β-coefficient: 21.0; 95% CI: 4.4–37.5; <i>n</i> = 117 paired samples). No differences were seen in plasma IL-6, CRP and IL-1Ra in patients by treatment group. <i>IL1B</i>, <i>IL6</i>, and <i>IL1RN</i> transcripts in monocyte/macrophages correlated with respective protein concentrations in hematoma fluid.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Hematomal IL-1Ra within a week of ICH is independently associated with a good outcome at 1 year, supporting further investigation of IL-1Ra in ICH. IL-6 is independently associated with a good outcome at 1 year, which might suggest a role in enhancing repair and recovery. ANN NEUROL 2026;100:345–360</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"345-360"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Frailty Rather than Age Alone Mediates the Lack of Benefit for Endovascular Thrombectomy in the Elderly Population of the RESILIENT Trial","authors":"Rui Kleber do Vale Martins-Filho MD, PhD,&nbsp;Thiago Oscar Goulart MD, PhD,&nbsp;Octavio Marques Pontes-Neto MD, PhD,&nbsp;Fabricio O. Lima MD, PhD,&nbsp;Leticia C. Rebello MD,&nbsp;Mario B. Faria MD,&nbsp;Francisco Mont'Alverne MD, PhD,&nbsp;Bruno S. M. Parente MD,&nbsp;Leonardo A. Carbonera MD,&nbsp;Millene Rodrigues Camilo MD, PhD,&nbsp;Diego Bandeira MD,&nbsp;Gisele S. Silva MD, PhD,&nbsp;Viviane F. Zétola MD, PhD,&nbsp;Jamary M. Oliveira-Filho MD, PhD,&nbsp;Daniel C. Bezerra MD, PhD,&nbsp;David S. Liebeskind MD,&nbsp;Sheila Cristina Ouriques Martins MD, PhD,&nbsp;Raul G. Nogueira MD","doi":"10.1002/ana.78247","DOIUrl":"10.1002/ana.78247","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to determine whether baseline computed tomography (CT) markers of cerebral small vessel disease (cSVD), as a surrogate of brain frailty, explain the association between age and functional outcome, potentially accounting for the reduced apparent benefit of mechanical thrombectomy (MT) in elderly patients in the RESILIENT trial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>RESILIENT was a multicenter, prospective, randomized, open-label trial with blinded outcome assessment conducted in Brazil. Patients with anterior circulation large-vessel occlusion stroke were randomized to MT plus guideline-based care or guideline-based care alone, including intravenous alteplase when eligible. A vascular neurologist blinded to clinical data evaluated baseline CT scans for cSVD markers (leukoaraiosis, lacunes, and atrophy) to derive a composite cSVD score. Multivariable logistic regression identified independent predictors of good functional outcome (modified Rankin Scale [mRS] = 0–2 at 90 days). Treatment effects were assessed across subgroups defined by age (&lt;70 or ≥70 years) and cSVD score (0–1 vs 2–3). Mediation analysis quantified the indirect effect of age on outcome through cSVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with good outcomes were younger, had lower National Institutes of Health Stroke Scale (NIHSS) scores, better collaterals, lower glucose levels, lower cSVD burden, and were more frequently treated with MT. Independent predictors of good outcome included lower NIHSS, MT, lower cSVD score, and lower glucose levels. MT benefit was restricted to patients &lt;70 years with low cSVD burden (odds ratio [OR] = 4.16, 95% confidence interval [CI] = 1.6–10.4, <i>p</i> &lt; 0.01). No benefit was observed in older patients or in those with cSVD &gt; 1. Mediation analysis showed that cSVD significantly mediated the association between age and outcome (average causal mediation effect [ACME] = –0.003, 95% CI = –0.005 to 0.00, <i>p</i> = 0.010).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Baseline CT markers of cSVD were independently associated with poorer outcomes and mediated the association between age and functional outcome in the RESILIENT trial, potentially explaining the lack of MT efficacy in older patients. ANN NEUROL 2026;100:361–369</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"361-369"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147865974","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":"Genetic-Proteomic Integration Identifies Predictive Plasma Proteins for Multiple Sclerosis","authors":"Yuan Ding MSc,&nbsp;Dylan Hamitouche,&nbsp;Simon Thebault MD, PhD,&nbsp;Patrick Kearns MBChB, MPH,&nbsp;Ahmed Abdelhak MD, PhD,&nbsp;Adil Harroud MD","doi":"10.1002/ana.78256","DOIUrl":"10.1002/ana.78256","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Multiple sclerosis (MS) develops after a prolonged preclinical phase. Identifying circulating biomarkers that capture this early biology can improve risk stratification and guide intervention. We aimed to identify plasma proteins driving MS susceptibility using large-scale proteogenomic integration and to evaluate their prediagnostic predictive value and effects on severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used cis-acting protein quantitative trait loci (pQTL) for 2,545 plasma proteins (n = 80,824). Predicted protein levels were tested for association with MS risk in 14,802 cases and 26,703 controls using Mendelian randomization and colocalization. Splicing annotations were integrated to interpret platform-specific discrepancies. We validated candidates as predictors of incident MS in prediagnostic United Kingdom Biobank samples (124 cases, 52,515 controls; median 5.9 years prediagnosis) and assessed associations with disease severity (n = 12,584).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 39 proteins associated with MS risk. Most formed a densely connected network enriched in immune regulatory pathways, B- and T-cell costimulation, cytokine signaling, and Epstein–Barr virus-related pathways. Transcriptomic enrichment was strongest in B-cell subsets. Splicing data suggested that discordances between proteomic platforms reflect distinct proteoforms. Among 28 genetically implicated proteins measured in prediagnostic samples, 8 were associated with time to MS diagnosis, demonstrating enrichment beyond chance expectation (<i>p</i>_binom = 4.92 × 10⁻⁵). DKKL1 showed concordant protective associations across risk, incidence, and severity. Integrating pQTLs improved fine-mapping resolution at colocalized loci by &gt;10-fold and nominated 13 putative novel risk loci.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This integrated genetic-proteomic framework identifies causal proteins, refines risk loci, and supports the development of early predictive biomarkers with translational potential. These findings support genetically anchored biomarkers for preclinical disease detection and intervention. ANN NEUROL 2026;100:268–281</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"268-281"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147985753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Memoriam: J. Richard Baringer, MD (1935–2025)","authors":"John E. Greenlee MD, FANA, FAAN,&nbsp;John W. Rose MD, FANA, FAAN,&nbsp;Kathleen B. Digre MD, FANA, FAAN, FAHS, FNANOS,&nbsp;Mark B. Bromberg MD, FANA, FAAN, FAANEM","doi":"10.1002/ana.78295","DOIUrl":"https://doi.org/10.1002/ana.78295","url":null,"abstract":"&lt;p&gt;Dr John Richard (Dick) Baringer died peacefully on July 22, 2025, bringing to a close a long and extraordinarily productive life within and beyond the field of neurology. Dick had celebrated a joyous 90th birthday on January 19, 2025, but then declined rapidly in health over the next several months. In his death, the world lost an outstanding clinician–scientist and human being.&lt;/p&gt;&lt;p&gt;Dick was born in Columbus, Ohio, on January 19, 1935. By age 10 years, at an age when many boys are dreaming of a life as a major professional athlete (or possibly a dreaded pirate), he knew that he wished to become a physician. He received his BS from the Ohio State University in 1955, and his MD from Case Western Reserve University in 1959. Dick trained at Massachusetts General Hospital from 1959 to 1968, first as Intern, Resident, and Fellow in Neurology and Resident in Pathology, and subsequently as Resident in Neurology and Fellow in Neuropathology. He became Assistant in Neurology and Instructor in Neuropathology in 1968.&lt;/p&gt;&lt;p&gt;In 1969, Dick moved to the University of California, San Francisco, as Assistant Chief of the Neurology Service at the Veterans Administration Hospital, San Francisco and as Assistant Professor in Residence, and then Assistant Professor in the Department of Neurology (1960–1973), progressing to Professor in Residence of Neurology and Pathology (1976–1982) and Chief of Neurology at the San Francisco Veterans Administration Hospital (1974–1982). From 1978 to 1979 Dick served as Acting Chair of Neurology at University of California, San Francisco.&lt;/p&gt;&lt;p&gt;While still in Boston, Dick had begun work on the neuropathology of herpes simplex virus encephalitis. Following his move to San Francisco, working with Kenneth Johnson, Stanley Prusiner, Jerry Wolinsky, and many other individuals, he built one of the world's premier programs in central nervous system infections and neurovirology.&lt;/p&gt;&lt;p&gt;In 1982, Dick was recruited to become Chair of the Department of Neurology at the University of Utah School of Medicine, assuming leadership of a department with a faculty of only 10 neurologists, limited national presence, and a tenuous residency program. On July 1, his first day as Chair, his secretary greeted him with: “Dr Baringer, we have a problem: one of the residents who was to join our program this morning has just resigned after being admitted to veterinary school.” Dick took this in his stride, recruited faculty carefully, made the program attractive to aspiring residents, and built strong research efforts in multiple areas, including neuroinfectious disease, neuroimmunology/multiple sclerosis, and neurogenetics. Over his tenure as Chair, he developed a nationally prominent department of over 50 individuals.&lt;/p&gt;&lt;p&gt;Academic medicine is often described as a three-legged stool, with the legs comprising patient care, teaching, and research. Dick excelled in each of these areas. He was a superb clinician across the broad field of neurology. He was a","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"235-237"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148533479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal Fluid Amyloid-β Biomarkers Predict Future Hemorrhage in Patients with Cerebral Amyloid Angiopathy","authors":"Philipp Arndt MD,&nbsp;Malte Pfister MD,&nbsp;Valentina Perosa MD,&nbsp;Hendrik Mattern PhD,&nbsp;Melis Tas MD,&nbsp;Lara Holzheimer MD,&nbsp;Johanna Engel MD,&nbsp;Marc Dörner MD,&nbsp;Marwa Al-Dubai MD,&nbsp;Cornelia Garz,&nbsp;Eya Khadhraoui MD,&nbsp;Sebastian J. Müller MD,&nbsp;Patrick Müller MD,&nbsp;Sven G. Meuth MD, PhD,&nbsp;Katja Neumann PhD,&nbsp;Stefanie Schreiber MD","doi":"10.1002/ana.78241","DOIUrl":"10.1002/ana.78241","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Accurately predicting future hemorrhagic events in patients with cerebral amyloid angiopathy (CAA) remains a major clinical challenge. It is unknown whether cerebrospinal fluid (CSF) biomarkers of amyloid-beta (Aβ) pathology are associated with increased hemorrhage risk in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed consecutive patients meeting Boston criteria version 2.0 for probable CAA with CSF Aβ data obtained during diagnostic workup. The primary outcome was incident intracranial hemorrhage, including lobar intracerebral, convexity subarachnoid, and non-traumatic subdural hemorrhage. Secondary outcomes were ischemic stroke and all-cause mortality. Associations between low CSF Aβ biomarkers and outcomes were analyzed using Cox proportional hazards models, adjusted for disseminated cortical superficial siderosis, and prior intracerebral hemorrhage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 109 patients (median age: 77 years, 42% female), 16 (15%) experienced incident intracranial hemorrhage and 11 (10%) incident ischemic stroke during a median follow-up of 2.93 years (interquartile range: 1.43–5.03). In multivariate Cox regression models low CSF Aβ biomarkers were independently associated with incident intracranial hemorrhage (Aβ₄₀: hazard ratio: 8.04; [95% CI: 2.43–26.59], <i>p</i> &lt; 0.001; Aβ₄₂: hazard ratio 7.10; [95% CI: 1.58–32.00], <i>p</i> = 0.011). CSF Aβ biomarkers were not associated with incident ischemic strokes and all-cause mortality. A composite risk score integrating low CSF Aβ biomarkers and hemorrhagic imaging features identified a high-risk subgroup with 78% hemorrhage incidence (7/9 patients) and a no-risk group without events (0/42 patients).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Low CSF Aβ biomarkers are independently associated with future symptomatic hemorrhage in CAA patients. A composite risk score may support individualized risk stratification and guide clinical decision-making. ANN NEUROL 2026;100:391–399</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"391-399"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Amyloid Beta and Tau Associations with Cerebral Amyloid Angiopathy Presence and Severity","authors":"Francesco Bax MD,&nbsp;Lei Liu MD, PhD,&nbsp;Thijs Wijnzen van Harten PhD,&nbsp;Elif Gokcal MD,&nbsp;Mitchell Jacob Horn MSc,&nbsp;Andrew Warren BS,&nbsp;Adriana Saba MS,&nbsp;Zahra Shirzadi PhD,&nbsp;Zora Y DiPucchio BA,&nbsp;Kristin M Schwab BA,&nbsp;Mahmut Edip Gurol MD, MSc,&nbsp;Anand Viswanathan MD,&nbsp;Jasmeer P Chhatwal MD, PhD,&nbsp;Steven Mark Greenberg MD, PhD","doi":"10.1002/ana.78264","DOIUrl":"10.1002/ana.78264","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim was to determine whether plasma amyloid beta (Aβ) Aβ37, Aβ40, Aβ42, and p-tau217 differ in cerebral amyloid angiopathy (CAA) from controls and associate with specific magnetic resonance imaging (MRI) markers of CAA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single center hospital-based study (Massachusetts General Hospital) enrolling patients with probable or definite CAA per Boston 2.0 criteria among consecutive individuals presenting with spontaneous intracerebral hemorrhage (ICH) and non-acute ICH related symptoms. Control participants were identified among individuals 55 years or older without history of ICH attending outpatient clinics in the same catchment area and time as the CAA cases. Primary outcome tested whether plasma Aβ37, Aβ40, Aβ42, and p-tau217 differ between patients with CAA and controls. Secondary outcome evaluated the correlation with the severity of selected CAA neuroradiological hallmarks on brain MRI scans obtained within 1 year of sample collection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 186 patients with CAA (mean age, 71.2 ± 8.3 years; males, 107 [58%]) and 401 controls (mean age, 73.9 ± 8.3 years; males, 211 [53%]) were included in the study. CAA cases had lower Aβ40 (β = −0.60, 95% CI = −0.80 to −0.40, <i>P</i> &lt; 0.001), Aβ42 (β = −0.48, 95% CI = −0.70 to −0.27, <i>P</i> &lt; 0.001), and higher p-tau217 (β = 0.73, 95 %CI = 0.54 to 0.91, <i>P</i> &lt; 0.001) concentrations compared to controls. Aβ40 was the only fragment reduced independent of ptau217 levels. Within the CAA group, biomarkers were associated with both hemorrhagic (reduced Aβ42 with cortical superficial siderosis) and non-hemorrhagic (reduced Aβ40 and Aβ42 with enlarged perivascular spaces in centrum semiovale, reduced Aβ37 and increased p-tau217 with white matter hyperintensities) MRI hallmarks of CAA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Plasma Aβ40, Aβ42, and p-tau217 differ between CAA patients and controls and are informative on CAA severity as inferred from brain MRI markers. ANN NEUROL 2026;100:380–390</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"380-390"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154341","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}