{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:52:33Z","timestamp":1781880753898,"version":"3.54.5"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003995","name":"Anhui Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["1908085MH249"],"award-info":[{"award-number":["1908085MH249"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Spinal muscular atrophy (SMA) is a neurodegenerative disorder characterized by the degeneration of motor neurons in the spinal cord. It remains uncertain whether the cognitive performance of adult patients with SMA is impaired. The objective of this study was to assess the cognitive profile of adult Chinese patients with SMA and the association between clinical features and cognitive ability, particularly executive function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This cross-sectional study included 22 untreated adult patients with type III SMA and 20 healthy subjects. The following variables were assessed: general intelligence, memory, attention, language, executive function, depression, anxiety, and other demographic and clinical parameters. In addition, physical function was evaluated using the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), and the 6-Minute Walk Test (6MWT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SMA patients had lower scores than healthy subjects in the Verbal Fluency Test, Stroop effect, Total Errors, Perseverative Responses, Perseverative Errors, and Non-perseverative Errors in the Wisconsin Card Sorting Test, showing impaired abilities of SMA patients in executive function. In the Attention Network Test (ANT), the results indicated that the SMA patients also had selective deficits in their executive control networks. Ambulant patients had better executive function test performance than non-ambulant ones. Compromised executive abilities in patients with SMA were correlated with a younger age at onset, poorer motor function, and higher levels of anxiety and depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study presented the distribution of cognitive impairment in a Chinese cohort with SMA. Patients with type III SMA showed selective deficits in executive function, which may be associated with disease severity, physical impairment, depression and anxiety. Future cognitive studies, accounting for motor and emotional impairment, are needed to evaluate if executive impairment is driven by specific brain changes or by those confounding factors.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1226043","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T10:30:00Z","timestamp":1699007400000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Cognitive impairment in Chinese adult patients with type III spinal muscular atrophy without disease-modifying treatment"],"prefix":"10.3389","volume":"14","author":[{"given":"Ying","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aonan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjuan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/s1474-4422(21)00367-7","article-title":"Safety and efficacy of once-daily Risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (sunfish part 2): a phase 3, double-blind, randomised","volume":"21","author":"Mercuri","year":"2022","journal-title":"Placebo-Controlled Trial Lancet Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/j.jmoldx.2016.05.004","article-title":"Mutation Spectrum of the survival of motor neuron 1 and functional analysis of variants in Chinese spinal muscular atrophy","volume":"18","author":"Qu","year":"2016","journal-title":"J molecular diagnostics: JMD"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/s1474-4422(12)70061-3","article-title":"Childhood spinal muscular atrophy: controversies and challenges","volume":"11","author":"Mercuri","year":"2012","journal-title":"Lancet Neurol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"487","DOI":"10.3233\/jnd-160177","article-title":"Type 0 spinal muscular atrophy: further delineation of prenatal and postnatal features in 16 patients","volume":"3","author":"Grotto","year":"2016","journal-title":"J Neuromus Dis"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1080\/1028415x.2020.1871212","article-title":"Nutrition status survey of type 2 and 3 spinal muscular atrophy in Chinese population","volume":"25","author":"Zhou","year":"2022","journal-title":"Nutr Neurosci"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1002\/mus.26201","article-title":"Social participation of adult patients with spinal muscular atrophy: frequency, restrictions, satisfaction, and correlates","volume":"58","author":"Kruitwagen-van Reenen","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.2147\/tcrm.s172291","article-title":"Clinical evidence supporting early treatment of patients with spinal muscular atrophy: current perspectives","volume":"15","author":"Dangouloff","year":"2019","journal-title":"Ther Clin Risk Manag"},{"key":"ref8","first-page":"544","article-title":"Downward shift in Iq in persons with Duchenne muscular dystrophy compared to those with spinal muscular atrophy","volume":"93","author":"Ogasawara","year":"1989","journal-title":"American J mental retardation: AJMR"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/s0960-8966(02)00048-2","article-title":"Cognitive function in children with spinal muscular atrophy","volume":"12","author":"Sieratzki","year":"2002","journal-title":"Neuromus Disord: NMD"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.3390\/brainsci11091184","article-title":"Cognitive impairment in adult patients with 5q-associated spinal muscular atrophy","volume":"11","author":"Kizina","year":"2021","journal-title":"Brain Sci"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.nmd.2022.05.005","article-title":"Cognitive profiles and clinical factors in type III spinal muscular atrophy: a preliminary study","volume":"32","author":"Lenzoni","year":"2022","journal-title":"Neuromus Disord: NMD"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.3389\/fneur.2019.01098","article-title":"Patient-reported prevalence of non-motor symptoms is low in adult patients suffering from 5q spinal muscular atrophy","volume":"10","author":"G\u00fcnther","year":"2019","journal-title":"Front Neurol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.nmd.2017.01.017","article-title":"Matching pairs difficulty in children with spinal muscular atrophy type I","volume":"27","author":"Polido","year":"2017","journal-title":"Neuromus Disord: NMD"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1590\/1980-57642018dn13-040011","article-title":"Cognitive performance of children with spinal muscular atrophy: a systematic review","volume":"13","author":"Polido","year":"2019","journal-title":"Dementia & neuropsychologia"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1089\/gtmb.2014.0002","article-title":"Subtle mutation detection of Smn1 gene in Chinese spinal muscular atrophy patients: implication of molecular diagnostic procedure for Smn1 gene mutations","volume":"18","author":"Bai","year":"2014","journal-title":"Genet Test Mol Biomarkers"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13023-020-01661-9","article-title":"Executive function is inversely correlated with physical function: the cognitive profile of adult spinal muscular atrophy (Sma)","volume":"16","author":"Mix","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e0172346","DOI":"10.1371\/journal.pone.0172346","article-title":"Revised Hammersmith scale for spinal muscular atrophy: a Sma specific clinical outcome assessment tool","volume":"12","author":"Ramsey","year":"2017","journal-title":"PloS One"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1002\/mus.25430","article-title":"Revised upper limb module for spinal muscular atrophy: development of a new module","volume":"55","author":"Mazzone","year":"2017","journal-title":"Muscle Nerve"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3233\/prm-160360","article-title":"Physical therapy services received by individuals with spinal muscular atrophy (SMA)","volume":"9","author":"Dunaway","year":"2016","journal-title":"J Pediatr Rehabil Med"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1080\/21678421.2020.1732424","article-title":"An overview of screening instruments for cognition and behavior in patients with Als: selecting the appropriate tool for clinical practice","volume":"21","author":"Gosselt","year":"2020","journal-title":"Amyotrophic lateral sclerosis & frontotemporal degeneration"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1001\/archneur.56.3.303","article-title":"Mild cognitive impairment: clinical characterization and outcome","volume":"56","author":"Petersen","year":"1999","journal-title":"Arch Neurol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.cortex.2021.03.005","article-title":"Cognitive reserve and regional brain volume in amyotrophic lateral sclerosis","volume":"139","author":"Temp","year":"2021","journal-title":"Cortex; a journal devoted to the study of the nervous system and behavior"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"395","DOI":"10.3389\/fneur.2017.00395","article-title":"Mismatch negativity as an Indicator of cognitive sub-domain dysfunction in amyotrophic lateral sclerosis","volume":"8","author":"Iyer","year":"2017","journal-title":"Front Neurol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1037\/neu0000413","article-title":"Word-list intrusion errors predict progression to mild cognitive impairment","volume":"32","author":"Thomas","year":"2018","journal-title":"Neuropsychology"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1162\/089892902317361886","article-title":"Testing the efficiency and Independence of attentional networks","volume":"14","author":"Fan","year":"2002","journal-title":"J Cogn Neurosci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1146\/annurev-neuro-062111-150525","article-title":"The attention system of the human brain: 20 years after","volume":"35","author":"Petersen","year":"2012","journal-title":"Annu Rev Neurosci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1471-2202-2-14","article-title":"Assessing the heritability of attentional networks","volume":"2","author":"Fan","year":"2001","journal-title":"BMC Neurosci"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1744-9081-9-23","article-title":"Effects of painful stimulation and acupuncture on attention networks in healthy subjects","volume":"9","author":"Liu","year":"2013","journal-title":"Behav Brain Functions: BBF"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1080\/01688639608408991","article-title":"Discriminability of the Wisconsin card sorting test using the standardization sample","volume":"18","author":"Axelrod","year":"1996","journal-title":"J Clin Exp Neuropsychol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.bandc.2009.03.005","article-title":"The Wisconsin card sorting test and the cognitive assessment of prefrontal executive functions: a critical update","volume":"71","author":"Nyhus","year":"2009","journal-title":"Brain Cogn"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.3390\/jcm9082605","article-title":"A computational study of executive dysfunction in amyotrophic lateral sclerosis","volume":"9","author":"Steinke","year":"2020","journal-title":"J Clin Med"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.jad.2012.12.001","article-title":"What does the Hamd mean?","volume":"148","author":"Leucht","year":"2013","journal-title":"J Affect Disord"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s12888-020-02560-w","article-title":"Reliability, validity and cut-off score of the Chinese version of the panic disorder severity scale self-report form in patients with panic disorder","volume":"20","author":"Liu","year":"2020","journal-title":"BMC Psychiatry"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3760\/cma.j.issn.0254-6450.2017.01.021","article-title":"Reliability and validity of depression scales of Chinese version: a systematic review","volume":"38","author":"Sun","year":"2017","journal-title":"Zhonghua liuxingbingxue zazhi"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/s0960-8966(01)00274-7","article-title":"Intelligence and cognitive function in children and adolescents with spinal muscular atrophy","volume":"12","author":"von Gontard","year":"2002","journal-title":"Neuromus Disord: NMD"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e548","DOI":"10.1542\/peds.2004-0668","article-title":"Spinal muscular atrophy: survival pattern and functional status","volume":"114","author":"Chung","year":"2004","journal-title":"Pediatrics"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3390\/brainsci11010008","article-title":"Cognitive performance of patients with adult 5q-spinal muscular atrophy and with amyotrophic lateral sclerosis","volume":"11","author":"Osmanovic","year":"2020","journal-title":"Brain Sci"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1016\/j.celrep.2017.01.035","article-title":"Single-cell analysis of Smn reveals its broader role in neuromuscular disease","volume":"18","author":"Rodriguez-Muela","year":"2017","journal-title":"Cell Rep"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"521","DOI":"10.3389\/fpsyg.2014.00521","article-title":"Self-locomotion and spatial language and spatial cognition: insights from typical and atypical development","volume":"5","author":"Oudgenoeg-Paz","year":"2014","journal-title":"Front Psychol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s11065-006-9002-x","article-title":"Executive function and the frontal lobes: a Meta-analytic review","volume":"16","author":"Alvarez","year":"2006","journal-title":"Neuropsychol Rev"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"80","DOI":"10.3390\/brainsci11010080","article-title":"Gray matter morphometry correlates with attentional efficiency in Young-adult multiple sclerosis","volume":"11","author":"Govindarajan","year":"2020","journal-title":"Brain Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/j.parkreldis.2015.08.035","article-title":"Selective attentional deficit in essential tremor: evidence from the attention network test","volume":"21","author":"Pauletti","year":"2015","journal-title":"Parkinsonism Relat Disord"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"7406","DOI":"10.1073\/pnas.0732088100","article-title":"Mapping the genetic variation of executive attention onto brain activity","volume":"100","author":"Fan","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.wneu.2016.10.095","article-title":"Neurocognitive function surrounding the resection of frontal who grade I Meningiomas: a prospective matched-control study","volume":"98","author":"Hendrix","year":"2017","journal-title":"World Neurosurg"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"3629","DOI":"10.1093\/hmg\/ddi390","article-title":"The activity of the spinal muscular atrophy protein is regulated during development and cellular differentiation","volume":"14","author":"Gabanella","year":"2005","journal-title":"Hum Mol Genet"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1111\/j.1440-1789.2008.00910.x","article-title":"An autopsy case of spinal muscular atrophy type III (Kugelberg-Welander disease)","volume":"29","author":"Kuru","year":"2009","journal-title":"Neuropathol: Official J Japanese Society Neuropathol"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1111\/neup.12784","article-title":"Spinal muscular atrophy type 2 patient who survived 61 years: an autopsy case report","volume":"42","author":"Yamadera","year":"2022","journal-title":"Neuropathol: Official J Japanese Society Neuropathol"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1111\/j.1600-0404.1991.tb04982.x","article-title":"Brain atrophy in Werdnig-Hoffmann disease","volume":"84","author":"Yohannan","year":"1991","journal-title":"Acta Neurol Scand"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"101618","DOI":"10.1016\/j.nicl.2018.101618","article-title":"The spinal and cerebral profile of adult spinal-muscular atrophy: a multimodal imaging study","volume":"21","author":"Querin","year":"2019","journal-title":"NeuroImage Clinical"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1097\/nen.0000000000000144","article-title":"Spectrum of Neuropathophysiology in spinal muscular atrophy type I","volume":"74","author":"Harding","year":"2015","journal-title":"J Neuropathol Exp Neurol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1186\/s12883-015-0473-3","article-title":"Understanding the experiences and needs of individuals with spinal muscular atrophy and their parents: a qualitative study","volume":"15","author":"Qian","year":"2015","journal-title":"BMC Neurol"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s13023-021-01701-y","article-title":"\"I have SMA Doesn't have me\": a qualitative snapshot into the challenges, successes, and quality of life of adolescents and Young adults with SMA","volume":"16","author":"Mazzella","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1002\/mus.25148","article-title":"Correlates of health related quality of life in adult patients with spinal muscular atrophy","volume":"54","author":"Kruitwagen-Van Reenen","year":"2016","journal-title":"Muscle Nerve"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1186\/s13023-021-02008-8","article-title":"Anxiety and depression in school-age patients with spinal muscular atrophy: a cross-sectional study","volume":"16","author":"Yao","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1249\/jsr.0000000000000169","article-title":"The cognitive benefits of exercise in youth","volume":"14","author":"Diamond","year":"2015","journal-title":"Curr Sports Med Rep"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1542\/peds.2018-4032","article-title":"The impact of physical activity on brain structure and function in youth: a systematic review","volume":"144","author":"Valkenborghs","year":"2019","journal-title":"Pediatrics"},{"key":"ref57","first-page":"E41","article-title":"Gender effects on the clinical phenotype in Japanese patients with spinal muscular atrophy","volume":"63","author":"Ar Rochmah","year":"2017","journal-title":"Kobe J Med Sci"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1226043\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T10:30:07Z","timestamp":1699007407000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1226043\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,3]]},"references-count":57,"alternative-id":["10.3389\/fneur.2023.1226043"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2023.1226043","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,3]]},"article-number":"1226043"}}