Annals of Neurology最新文献

{"title":"Efficacy and Safety of Ofatumumab Treatment for Anti-NMDA Receptor Autoimmune Encephalitis (OFF-AE): A Prospective, Multicenter Cohort Study.","authors":"Kundian Guo, Fuhua Peng, Jia Liu, Youming Long, Shougang Guo, Honghao Wang, Gang Yu, Yanlin Zhang, Xiong Han, Ewen Tu, Yake Zheng, Jialu Huang, Yanxia Zhou, Dongmei An, Guanyan Lin, Baojie Wang, Yuanyuan Wang, Ping Yang, Yu Jiang, Beijia Cui, Zhenyu Yang, Maiqi Du, Meiling Jiang, Limin Qin, Xueying Kong, Xue Gong, Xu Liu, Linjun Cai, Jinmei Li, Dong Zhou, Zhen Hong","doi":"10.1002/ana.27218","DOIUrl":"https://doi.org/10.1002/ana.27218","url":null,"abstract":"<p><strong>Objective: </strong>Ofatumumab presents a potentially promising alternative to current second-line immunotherapy for refractory anti-N-methyl-D-aspartate receptor autoimmune encephalitis (NMDAR-AE). We aimed to evaluate the efficacy and safety of ofatumumab as a novel second-line immunotherapy for NMDAR-AE.</p><p><strong>Methods: </strong>This prospective, multicenter, nested cohort study compared patients with NMDAR-AE from the CHina Autoimmune encephalitiS outcomE study registry (CHASE) recruited between October 2011 and February 2024, treated with and without ofatumumab. The primary outcome was the proportion reaching a favorable functional outcome (modified Rankin Scale [mRS] score ≤2) at the last follow-up. Secondary outcomes included mRS scores and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores over the first 24-month follow-up and the proportion with further mRS score improvement after ofatumumab initiation. A propensity score matching was performed to balance major confounders.</p><p><strong>Results: </strong>A total of 715 patients with AE were screened. Fifty-eight propensity score-matched patients with NMDAR-AE each in the ofatumumab group and non-ofatumumab group were analyzed. Fifty-four patients (93.1%) in the ofatumumab group achieved further mRS score improvement with a median time of 14 days from ofatumumab initiation, and 53 (91.4%) reached a favorable functional outcome at the last follow-up. For those who failed first-line immunotherapy, the ofatumumab group demonstrated a faster mRS score and CASE score improvement and more frequently reached a favorable functional outcome at the last follow-up compared with the non-ofatumumab group (87.9% vs. 64.7%, odds ratio [OR] 3.95; 95% confidence interval [CI] 1.12-13.94; p = 0.026). No serious adverse events associated with ofatumumab treatment were reported.</p><p><strong>Interpretation: </strong>Ofatumumab showed substantial efficacy and safety, particularly in patients who failed first-line immunotherapy, warranting its consideration in NMDAR-AE management. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481799","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":"Regional Cerebral Atrophy Contributes to Personalized Survival Prediction in Amyotrophic Lateral Sclerosis: A Multicentre, Machine Learning, Deformation-Based Morphometry Study.","authors":"Isabelle Lajoie, Sanjay Kalra, Mahsa Dadar","doi":"10.1002/ana.27196","DOIUrl":"https://doi.org/10.1002/ana.27196","url":null,"abstract":"<p><strong>Objective: </strong>Accurate personalized survival prediction in amyotrophic lateral sclerosis is essential for effective patient care planning. This study investigates whether grey and white matter changes measured by magnetic resonance imaging can improve individual survival predictions.</p><p><strong>Methods: </strong>We analyzed data from 178 patients with amyotrophic lateral sclerosis and 166 healthy controls in the Canadian Amyotrophic Lateral Sclerosis Neuroimaging Consortium study. A voxel-wise linear mixed-effects model assessed disease-related and survival-related atrophy detected through deformation-based morphometry, controlling for age, sex, and scanner variations. Additional linear mixed-effects models explored associations between regional imaging and clinical measurements, and their associations with time to the composite outcome of death, tracheostomy, or permanent assisted ventilation. We evaluated whether incorporating imaging features alongside clinical data could improve the performance of an individual survival distribution model.</p><p><strong>Results: </strong>Deformation-based morphometry uncovered distinct voxel-wise atrophy patterns linked to disease progression and survival, with many of these regional atrophies significantly associated with clinical manifestations of the disease. By integrating regional imaging features with clinical data, we observed a substantial enhancement in the performance of survival models across key metrics. Our analysis identified specific brain regions, such as the corpus callosum, rostral middle frontal gyrus, and thalamus, where atrophy predicted an increased risk of mortality.</p><p><strong>Interpretation: </strong>This study suggests that brain atrophy patterns measured by deformation-based morphometry provide valuable insights beyond clinical assessments for prognosis. It offers a more comprehensive approach to prognosis and highlights brain regions involved in disease progression and survival, potentially leading to a better understanding of amyotrophic lateral sclerosis. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476165","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":"Fluoxetine Treatment in Epilepsy of Infancy with Migrating Focal Seizures Due to KCNT1 Variants: An Open Label Study.","authors":"Marina Trivisano, Ilaria Mosca, Licia Salimbene, Angela De Dominicis, Paolo Ambrosino, Deborah Puzo, Ilenio Servettini, Cinzia Correale, Chiara Falamesca, Cristina Filosomi, Bianca Goffredo, Maria Virginia Soldovieri, Maurizio Taglialatela, Nicola Specchio","doi":"10.1002/ana.27213","DOIUrl":"https://doi.org/10.1002/ana.27213","url":null,"abstract":"<p><strong>Objective: </strong>Gain-of-function (GoF) variants in KCNT1 encoding for potassium channels are associated with different epilepsy phenotypes, including epilepsy of infancy with migrating focal seizures (EIMFS), other early infantile developmental and epileptic encephalopathies, and focal epilepsy. Fluoxetine blocks currents from both wild-type (WT) and mutant KCNT1 channels with GoF in vitro features. In this study, we tested the hypothesis that treatment with fluoxetine might improve clinical outcome in patients with EIMFS carrying GoF variants in KCNT1 channels showing in vitro sensitivity to fluoxetine blockade.</p><p><strong>Methods: </strong>We enrolled three pediatric patients carring de novo KCNT1 genetic variants linked to EIMFS. Functional and pharmacological studies to assess fluoxetine's ability to counteract in vitro variant-induced functional effects were performed with patch-clamp electrophysiology on heterologous channel expression in mammalian Chinese hamster ovary cells. Neuropsychological assessment, electroencephalogram and seizure diary were evaluated at baseline and every 3 months during the study. Electrocardiography and blood levels of medications were monitored for safety.</p><p><strong>Results: </strong>All 3 KCNT1 variants displayed GoF effects in vitro. Exposure to fluoxetine (10μM) blocked both WT and mutant KCNT1 channels, therefore, counteracting variant-induced functional effects. Treatment with fluoxetine caused a variable reduction of seizure frequency (25-75%). Improvement in visual attention, participation, and muscle tone was also reported. No adverse events were reported except for transient dyskinesia in 1 patient, which was probably related to an increase in fluoxetine plasma level.</p><p><strong>Interpretation: </strong>Fluoxetine may be a potential targeted medication in EIMFS caused by KCNT1 GoF variants. Further research is needed to assess its long-term efficacy and safety. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466685","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":"Cyclic Alternating Pattern Dynamics in Individuals at Risk for Developing Parkinson's Disease.","authors":"Andrew Dagay, Shlomit Katzav, Danielle Wasserman, Valentina Gnoni, Anat Mirelman, Riva Tauman","doi":"10.1002/ana.27217","DOIUrl":"https://doi.org/10.1002/ana.27217","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to investigate the differences in cyclic alternating patterns (CAP) metrics, a non-rapid eye movement (NREM) sleep physiological rhythm, among recently diagnosed patients with Parkinson's disease (PD), and individuals at high and low risk for developing PD based on genetic and prodromal risk.</p><p><strong>Methods: </strong>In this cross-sectional exploratory study, participants underwent clinical, cognitive, and motor evaluation to compute risk based on the Movement Disorder Society (MDS) prodromal criteria and a standard overnight polysomnography. CAP rate, CAP index, A index subtypes, number of CAP sequences, and CAP sequence duration were computed from the electroencephalogram (EEG) signal.</p><p><strong>Results: </strong>The study included 30 patients with early PD (mean age = 62.80 ± 7.69, disease duration = 1.10 ± 1.09), 26 participants at risk for PD (age = 64.88 ± 10.09), and 36 participants with low risk for PD (age = 56.83 ± 7.41). Despite comparable macrosleep architecture, most CAP measures were significantly lower in patients with PD compared with the low-risk group, whereas the at-risk group showed transitional values between PD and the low-risk group. The A2 index was significantly lower in both the at-risk and PD groups from the low-risk group (at risk = 7.59 ± 4.59; PD = 7.71 ± 5.83; and low risk = 12.85 ± 8.63; p = 0.010). Lower CAP rate and lower CAP index were associated with greater disease severity (r = -0.23 and - 0.24, respectively).</p><p><strong>Interpretation: </strong>Patients with early clinical PD exhibit alterations in CAP dynamics despite having comparable macrosleep architecture. Alterations of the NREM microsleep structure may occur early in the neurodegenerative process and the A2 index may be an early event in the evolution of the disease with the potential to serve as an early marker for disease progression. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466683","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":"Distinct Alterations of Inflammatory Biomarkers in Cluster Headache: A Case Control Study.","authors":"Nunu Laura Timotheussen Lund, Connar Stanley James Westgate, Marie-Louise Kulas Søborg, Agneta Henriette Snoer, Rigmor Højland Jensen, Thomas Folkman Hansen, Anja Sofie Petersen","doi":"10.1002/ana.27205","DOIUrl":"https://doi.org/10.1002/ana.27205","url":null,"abstract":"<p><strong>Objective: </strong>Investigate the immune system's role in cluster headache by analyzing cytokines in people with cluster headache and headache-free controls, and explore if certain cytokines could predict a specific phenotype.</p><p><strong>Methods: </strong>We measured 45 cytokines in adult participants from the Danish Cluster Headache Biobank in a prospective case-control setup. People with cluster headache were diagnosed according to the International Classification of Headache Disorders third-edition. Controls were matched for age and sex.</p><p><strong>Results: </strong>A total of 412 were analyzed deriving from 99 with chronic cluster headache, 108 with episodic cluster headache (ECH) in bout, 105 with ECH in remission, and 100 successfully matched controls. Compared with controls, 13 cytokines were altered for ECH in bout (p < 0.05), 3 in remission (p < 0.05), and 10 for chronic cluster headache (p < 0.05). Oncostatin m was significantly elevated in all 3 disease states compared with controls (p < 0.05). Overall, the investigated cytokines showed distinct patterns of alterations between chronic cluster headache and episodic cluster headache in bout and, interestingly, IL-1β was significantly associated with having chronic cluster headache rather than episodic in bout in a logistic regression model adjusting for potential confounders (p < 0.05).</p><p><strong>Interpretation: </strong>Findings show that the immune system is altered in all 3 states of cluster headache compared with controls. Oncostatin m was elevated, constituting a promising target for future studies. The distinct alterations between episodic and chronic cluster headache are striking and urges further research of the immune system in cluster headache to better understand its potential role in prediction of disease activity and treatment response. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466684","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":"Longitudinal Metabolomics in Amyotrophic Lateral Sclerosis Implicates Impaired Lipid Metabolism.","authors":"Kai Guo, Masha G Savelieff, Dae-Gyu Jang, Samuel J Teener, Lili Zhao, Junguk Hur, Stephen A Goutman, Eva L Feldman","doi":"10.1002/ana.27208","DOIUrl":"https://doi.org/10.1002/ana.27208","url":null,"abstract":"<p><strong>Objective: </strong>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by altered metabolome and energy homeostasis, manifesting with body mass index changes and hypermetabolism-both prognostic of disease progression and survival. The cross-sectional ALS metabolome has been characterized, but longitudinal correlations to functional decline are lacking.</p><p><strong>Methods: </strong>We longitudinally evaluated metabolomes from ALS plasma and terminal postmortem spinal cord and brain motor cortex tissue. We constructed 3 plasma models. A linear mixed effects model correlated all metabolite levels across all timepoints to their corresponding functional scores. An interaction model predicted a longitudinal change in function from baseline metabolites, whereas a progression model identified metabolites linked to a 20% or 50% drop in function. In postmortem samples, differential metabolites in onset versus second spinal cord segments served as a surrogate of disease progression. Mendelian randomization assessed potential causality from metabolites.</p><p><strong>Results: </strong>In plasma, all models primarily selected lipid metabolites and sub-pathways, in addition to amino acids, xenobiotics, and various less frequently selected pathways. Among lipids, fatty acids and sphingomyelins were predominant, along with plasmalogens, phosphatidylcholines, and lysophospholipids. Sex interaction findings were nominal. In the spinal cord, sphingomyelin and long-chain saturated and monounsaturated fatty acids were more abundant in the onset segment tissue, whereas phosphatidylcholines and phosphatidylethanolamines were less abundant. Mendelian randomization suggested that impaired carnitine and short chain acylcarnitine metabolism may be genetically determined in ALS, along with various antioxidant derivatives.</p><p><strong>Interpretation: </strong>Our findings suggest metabolomic changes primarily involving different lipid classes and carnitine metabolism may underscore ALS severity and progression. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456425","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":"Brain Metabolic Features of FUS-ALS: A 2-[¹⁸F]FDG-PET Study.","authors":"Antonio Canosa, Umberto Manera, Rosario Vasta, Grazia Zocco, Francesca Di Pede, Sara Cabras, Filippo De Mattei, Francesca Palumbo, Barbara Iazzolino, Emilio Minerva, Luca Sbaiz, Maura Brunetti, Salvatore Gallone, Maurizio Grassano, Enrico Matteoni, Giulia Polverari, Giuseppe Fuda, Federico Casale, Paolina Salamone, Giovanni De Marco, Giulia Marchese, Cristina Moglia, Andrea Calvo, Marco Pagani, Adriano Chiò","doi":"10.1002/ana.27201","DOIUrl":"https://doi.org/10.1002/ana.27201","url":null,"abstract":"<p><strong>Objective: </strong>We aimed at evaluating the brain metabolic features of fused in sarcoma amyotrophic lateral sclerosis (FUS-ALS) compared with sporadic ALS (sALS), using 2-[fluorine-18] fluoro-2-deoxy-D-glucose positron emission tomography (2-[¹⁸F]FDG-PET).</p><p><strong>Methods: </strong>We employed the 2-sample t-test model of SPM12, implemented in MATLAB, to compare 12 FUS-ALS cases with 40 healthy controls (HC) and 48 sALS, randomly collected from the series of patients who underwent brain 2-[¹⁸F]FDG-PET at the ALS Center of Turin (Italy) at diagnosis from 2009 to 2019. In the comparisons between cases and HC, we included age at PET and sex as covariates. Because FUS-ALS usually shows early onset in spinal regions, in the comparison between FUS-ALS and sALS, we included singularly the following covariates in a second step, to evaluate the determinants of eventual metabolic differences: age at PET, sex, and onset (spinal/bulbar).</p><p><strong>Results: </strong>sALS patients showed significant relative hypometabolism in bilateral fronto-temporo-occipital cortex and right insula as compared with FUS-ALS. After adjusting for age, the relative hypometabolism remained in the bilateral precentral gyrus and in the right middle and inferior temporal gyrus. As compared with HC, FUS patients displayed a significant relative hypermetabolism in the pontobulbar region and right cerebellar tonsil, dentate nucleus, and uvula, while sALS showed relative hypometabolism in bilateral frontal and occipital cortices and in left temporal and parietal regions.</p><p><strong>Interpretation: </strong>Patients with FUS-ALS show relative preservation of motor cortex metabolism compared with those with sALS, possibly reflecting the prevalence of lower motor neuron impairment in their phenotype. Prospective studies are necessary to investigate the possible role of 2-[¹⁸F]FDG-PET as a biomarker to track disease spreading in clinical trials. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456422","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":"A Multicenter Study of Hereditary Transthyretin Amyloidosis in China.","authors":"Xujun Chu, Juan Kang, Jingwen Xu, Haishan Jiang, Zhi-Ying Wu, Qingping Wang, Wei Li, Jia Li, Xinghua Luan, Chong Sun, Zhangyu Zou, Min Zhu, Bin Chen, Xiaoxuan Liu, Meihong Zhou, Kang Du, Tao Huang, Dongsheng Fan, Zaiqiang Zhang, Daojun Hong, Jie Lin, Li Cao, Min Qian, Zhaoxia Wang, Yun Yuan, Yuwei Da, Hao Yu, Ruxu Zhang, Lingchao Meng","doi":"10.1002/ana.27203","DOIUrl":"https://doi.org/10.1002/ana.27203","url":null,"abstract":"<p><strong>Objective: </strong>Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant genetic disease characterized by the misfolding and deposition of the transthyretin (TTR) protein. This study aimed to describe the clinical and genetic characteristics of ATTRv in a large multicenter Chinese cohort.</p><p><strong>Methods: </strong>Patients from 14 centers were included in the study. The clinical and genetic characteristics of all patients were summarized. The peripheral blood white blood cell mitochondrial DNA (mtDNA) was detected in offspring from different genders.</p><p><strong>Results: </strong>A total of 202 individuals with ATTRv from 148 families were identified. The average age of onset was 50.6 ± 12.4 years. Among these cases, 117 (57.9%) were classified as late-onset (≥50 years) and 85 (42.1%) as early-onset. Overall, the length dependent axonal sensorimotor peripheral neuropathy was the predominant phenotype (89.1%). A total of 42 heterozygous missense variants and 1 deletion variant were identified. The most common variants were Val30Met (19.8%) and Ala97Ser (15.8%) and patients with Val30Met and Ala97Ser were mostly late-onset in our cohort. Thirty-nine of these patients died with a mean age of 56.1 ± 13.5 years. Anticipation according to gender groups of offspring-parent pairs was different, and mother-son pairs showed the largest anticipation. The copies of mtDNA in the mother's offspring outnumbered those of the father's offspring (p < 0.001).</p><p><strong>Interpretation: </strong>This study highlights that ATTRv patients in China exhibit high heterogeneity in their initial symptoms. The most common variants observed in this cohort is Val30Met. The mtDNA copy number shows gender-linked effects. These results can impact ATTRv diagnosis and patient care strategies. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456416","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":"Post-Dissection Double Carotid Lumen With Inversed Slow Flow in the False Lumen Associated with Stroke.","authors":"Dimitri Renard, Salim Allal, Perrine Schmitt","doi":"10.1002/ana.27221","DOIUrl":"https://doi.org/10.1002/ana.27221","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456426","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":"The Use of Antihypertensive Medication and In Vivo Alzheimer's Disease Pathology.","authors":"Musung Keum, Min Soo Byun, Dahyun Yi, Hyejin Ahn, Gijung Jung, Joon Hyung Jung, Nayeong Kong, Jun-Young Lee, Yu Kyeong Kim, Yun-Sang Lee, Koung Mi Kang, Chul-Ho Sohn, Dong Young Lee","doi":"10.1002/ana.27204","DOIUrl":"https://doi.org/10.1002/ana.27204","url":null,"abstract":"<p><strong>Objective: </strong>We investigated whether the use of antihypertensive medication (AHM) is associated with in vivo Alzheimer's Disease (AD) pathologies in older adults with hypertension and examined if the effect differs by drug-class and blood-brain barrier (BBB) permeability of the drug.</p><p><strong>Methods: </strong>This cross-sectional study recruited participants from the Korean Brain Aging Study for the Early Diagnosis and Prevention of Alzheimer's Disease. Participants comprised both cognitively normal and impaired older adults diagnosed with hypertension (n = 408). All participants underwent comprehensive clinical assessment and [¹¹C] Pittsburgh Compound B positron emission tomography (PET) for measurement of cerebral β-amyloid (Aβ) deposition. Additionally, a subset of participants (n = 120) was subjected to [¹⁸F] AV-1451 PET to assess tau deposition.</p><p><strong>Results: </strong>The AHM group (n = 227) exhibited significantly lower Aβ deposition (B [SE] = -0.104 [0.037], p = 0.006) compared to the non-AHM group (n = 181), even after controlling for age, sex, apolipoprotein E ε4-positivity, vascular risk factors, and mean arterial blood pressure. Further analysis by AHM class showed an association between the use of renin-angiotensin system inhibitors (RASi) and less Aβ deposition (B [SE] = -0.143[0.049], p = 0.004). No significant relationships were observed between the use of BBB-permeable AHM and Aβ deposition. Additionally, associations between AHM use and tau deposition did not reach statistical significance.</p><p><strong>Interpretation: </strong>Our findings suggest that AHM use may be associated with lower Aβ burden in older adults with hypertension. Further studies exploring the underlying mechanism, particularly related to RASi, may provide insights into new therapeutic targets for AD. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439619","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}