{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T07:11:43Z","timestamp":1783581103188,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"APHP"},{"name":"SAMG"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>This study sought to link neurocognitive profiles in sickle cell disease (SCD) patients with clinical characteristics. We conducted a prospective cohort study of adults with SCD who underwent comprehensive neuropsychological assessment at the UMGGR clinic at Henri Mondor Hospital, Cr\u00e9teil (France). A cluster analysis was performed based on neuropsychological testing scores. The association between clusters and clinical profiles was assessed. Between 2017 and 2021, 79 patients with a mean age of 36 [range 19\u201365] years were included. On principal component analysis, a 5-factor model presented the best fit (Bartlett\u2019s sphericity test [\u03c72 (171) = 1345; p &lt; 0.001]), explaining 72% of the variance. The factors represent distinct cognitive domains and anatomical regions. On hierarchical classification, three clusters emerged. Cluster 1 (n = 24) presented deficits in all five factors compared to Cluster 3 (n = 33). Cluster 2 (n = 22) had deficits in all factors, but to a lesser extent than Cluster 1. MoCA scores mirrored the severity of these cognitive deficits. Age, genotype and stroke prevalence did not differ significantly between clusters. However, the time of first stroke occurrence differed significantly between Cluster 1 and 2\u20133: 78% of strokes occurred during childhood, whereas 80% and 83% occurred during adulthood in Clusters 2 and 3, respectively. Educational attainment was also reduced in Cluster 1. SCD patients with childhood stroke seem to be at increased risk of a global cognitive deficit profile. In addition to existing methods of primary and secondary stroke prevention, early neurorehabilitation should be prioritized in order to reduce the long-term cognitive morbidity of SCD.<\/jats:p>","DOI":"10.3390\/jcm12041615","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T02:02:09Z","timestamp":1676858529000},"page":"1615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Early Strokes Are Associated with More Global Cognitive Deficits in Adults with Sickle Cell Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4747-082X","authenticated-orcid":false,"given":"Maryline","family":"Couette","sequence":"first","affiliation":[{"name":"Sickle Cell Referral Centre\u2013UMGGR, University of Paris Est Cr\u00e9teil, Henri Mondor APHP, 94010 Cr\u00e9teil, France"},{"name":"CARMAS (Cardiovascular and Respiratory Manifestations of Acute Lung Injury and Sepsis), University of Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France"},{"name":"IMRB, INSERM, University of Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2434-9234","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Fort\u00e9","sequence":"additional","affiliation":[{"name":"Department of Medecine, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H2X 0C1, Canada"},{"name":"Department of Medicine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3C 3J7, Canada"},{"name":"Centre de Recherche du CHUM, Montr\u00e9al, QC H2X 0A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3624-7251","authenticated-orcid":false,"given":"Damien","family":"Oudin Doglioni","sequence":"additional","affiliation":[{"name":"Sickle Cell Referral Centre\u2013UMGGR, University of Paris Est Cr\u00e9teil, Henri Mondor APHP, 94010 Cr\u00e9teil, France"},{"name":"Laboratoire Inter-Universitaire de Psychologie\u2014Personnalit\u00e9, Cognition, Changement Social (LIP\/PC2S), Universit\u00e9 Grenoble Alpes, 38058 Saint-Martin-d\u2032H\u00e8res, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armand","family":"Mekontso-Dessap","sequence":"additional","affiliation":[{"name":"CARMAS (Cardiovascular and Respiratory Manifestations of Acute Lung Injury and Sepsis), University of Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France"},{"name":"IMRB, INSERM, University of Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Calvet","sequence":"additional","affiliation":[{"name":"INSERM, UMR 1266, Psychiatry and Neurosciences Institute of Paris, Paris-Descartes University, Department of Neurology and Stroke Unit, Sainte-Anne Hospital, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6744-9238","authenticated-orcid":false,"given":"Kevin H. M.","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7007-1344","authenticated-orcid":false,"given":"Pablo","family":"Bartolucci","sequence":"additional","affiliation":[{"name":"Sickle Cell Referral Centre\u2013UMGGR, University of Paris Est Cr\u00e9teil, Henri Mondor APHP, 94010 Cr\u00e9teil, France"},{"name":"IMRB, INSERM, University of Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France"},{"name":"INSERM-U955, Equipe 2, Laboratoire d\u2019Excellence, GRex, Institut Mondor, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5S3","DOI":"10.1016\/S0248-8663(15)60002-9","article-title":"Centre de r\u00e9f\u00e9rence maladies rares \u00ab syndromes dr\u00e9panocytaires majeurs \u00bb [French guidelines for the management of adult sickle cell disease: 2015 update]","volume":"36","author":"Habibi","year":"2015","journal-title":"Rev. Med. Interne"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1136\/bmj.327.7424.1151","article-title":"Managing Sickle Cell Disease","volume":"327","author":"Claster","year":"2003","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1056\/NEJM199406093302303","article-title":"Mortality in Sickle Cell Disease. Life Expectancy and Risk Factors for Early Death","volume":"330","author":"Platt","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_4","first-page":"288","article-title":"Cerebrovascular Accidents in Sickle Cell Disease: Rates and Risk Factors","volume":"91","author":"Weiner","year":"1998","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1182\/blood-2014-09-599852","article-title":"Chronic and Acute Anemia and Extracranial Internal Carotid Stenosis are Risk Factors for Silent Cerebral Infarcts in Sickle Cell Anemia","volume":"125","author":"Bernaudin","year":"2015","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1182\/blood-2016-01-694562","article-title":"Silent Cerebral Infarcts and Cerebral Aneurysms are Prevalent in Adults with Sickle Cell Anemia","volume":"127","author":"Kassim","year":"2016","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1182\/blood-2011-05-349621","article-title":"Associated Risk Factors for Silent Cerebral Infarcts in Sickle Cell Anemia: Low Baseline Hemoglobin, Sex, and Relative High Systolic Blood Pressure","volume":"119","author":"DeBaun","year":"2012","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1001\/jama.2010.562","article-title":"Neuropsychological Dysfunction and Neuroimaging Abnormalities in Neurologically Intact Adults with Sickle Cell Anemia","volume":"303","author":"Vichinsky","year":"2010","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1080\/13803395.2016.1149153","article-title":"Cognitive Deficits are Associated with Unemployment in Adults with Sickle Cell Anemia","volume":"38","author":"Sanger","year":"2016","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1093\/jpepsy\/jsz031","article-title":"Cognitive Function in Sickle Cell Disease Across Domains, Cerebral Infarct Status, and the Lifespan: A Meta-Analysis","volume":"44","author":"Prussien","year":"2019","journal-title":"J. Pediatr. Psychol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sahu, T., Pande, B., Sinha, M., Sinha, R., and Verma, H.K. (2022). Neurocognitive Changes in Sickle Cell Disease: A Comprehensive Review. Ann. Neurosci., 09727531221108871.","DOI":"10.1177\/09727531221108871"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"744118","DOI":"10.3389\/fneur.2021.744118","article-title":"The Epidemiology of Neurological Complications in Adults with Sickle Cell Disease: A Retrospective Cohort Study","volume":"12","author":"Maduakor","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1212\/WNL.0000000000000188","article-title":"Neuroimaging Abnormalities in Adults with Sickle Cell Anemia: Associations with Cognition","volume":"82","author":"Mackin","year":"2014","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4172","DOI":"10.1182\/blood-2021-145808","article-title":"Neurocognitive Assessment of Adults with Sickle Cell Disease: A Descriptive Study","volume":"138","author":"Oluwole","year":"2021","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1182\/bloodadvances.2019001142","article-title":"American Society of Hematology 2020 Guidelines for Sickle Cell Disease: Prevention, Diagnosis, and Treatment of Cerebrovascular Disease in Children and Adults","volume":"4","author":"DeBaun","year":"2020","journal-title":"Blood Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e217039","DOI":"10.1001\/jamanetworkopen.2021.7039","article-title":"Screening for Cognitive Dysfunction Using the Rowland Universal Dementia Assessment Scale in Adults with Sickle Cell Disease","volume":"4","author":"Blais","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"560","DOI":"10.14423\/SMJ.0000000000000511","article-title":"Utility of the Montreal Cognitive Assessment as a Screening Test for Neurocognitive Dysfunction in Adults with Sickle Cell Disease","volume":"109","author":"Cichowitz","year":"2016","journal-title":"South Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/bjh.18188","article-title":"The Montreal Cognitive Assessment as a Cognitive Screening Tool in Sickle Cell Disease: Associations with Clinically Significant Cognitive Domains","volume":"198","author":"Early","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/WAD.0000000000000034","article-title":"Diagnostic Criteria for Vascular Cognitive Disorders: A VASCOG Statement","volume":"28","author":"Sachdev","year":"2014","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool for Mild Cognitive Impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1212\/WNL.38.6.900","article-title":"Screening for Dementia by Memory Testing","volume":"38","author":"Grober","year":"1988","journal-title":"Neurology"},{"key":"ref_22","unstructured":"Rey, A. (1959). Test de Copie et de Reproduction de M\u00e9moire de Figures G\u00e9om\u00e9triques Complexes, Editions du centre de psychologie appliqu\u00e9e."},{"key":"ref_23","unstructured":"(2021, November 13). WAIS-IV\u2014Echelle D\u2019intelligence De Wechsler Pour Adultes\u20144eme Edition. Available online: https:\/\/www.pearsonclinical.fr\/wais-iv-nouvelle-version-de-lechelle-dintelligence-de-wechsler-pour-adultes-quatrieme-edition."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1177\/1352458511435717","article-title":"Reliability and Equivalence of Alternate Forms for the Symbol Digit Modalities Test: Implications for Multiple Sclerosis Clinical Trials","volume":"18","author":"Benedict","year":"2012","journal-title":"Mult. Scler."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Brickenkamp, R., and Zillmer, E. (1998). The D2 Test of Attention, Hogrefe & Huber.","DOI":"10.1037\/t03299-000"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2466\/pms.1958.8.3.271","article-title":"Validity of the Trail Making Test as an Indicator of Organic Brain Damage","volume":"8","author":"Reitan","year":"1958","journal-title":"Percept. Mot. Ski."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1037\/h0054651","article-title":"Studies of Interference in Serial Verbal Reactions","volume":"18","author":"Stroop","year":"1935","journal-title":"J. Exp. Psychol."},{"key":"ref_28","first-page":"207","article-title":"Formal and semantic lexical evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level","volume":"90","author":"Cardebat","year":"1990","journal-title":"Acta. Neurol. Belg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3917\/rne.034.0235","article-title":"La batterie d\u2019\u00e9valuation des connaissances s\u00e9mantiques du GRECO (BECS-GRECO): Validation et donn\u00e9es normatives","volume":"3","author":"Merck","year":"2011","journal-title":"Rev. Neuropsychol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1600-0447.1983.tb09716.x","article-title":"The Hospital Anxiety and Depression Scale","volume":"67","author":"Zigmond","year":"1983","journal-title":"Acta. Psychiatr. Scand."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S2215-0366(19)30291-3","article-title":"Cognitive Function Following a Major Depressive Episode: A Systematic Review and Meta-Analysis","volume":"6","author":"Semkovska","year":"2019","journal-title":"Lancet Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v070.i01","article-title":"MissMDA: A Package for Handling Missing Values in Multivariate Data Analysis","volume":"70","author":"Josse","year":"2016","journal-title":"J. Stat. Softw."},{"key":"ref_33","unstructured":"R Core Team (2019). R: A Language and Environment for Statistical Computing, The R Foundation. version 3.6, Computer software."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1207\/s15327574ijt0502_4","article-title":"Minimum Sample Size Recommendations for Conducting Factor Analyses","volume":"5","author":"Mundfrom","year":"2005","journal-title":"Int. J. Test."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jalz.2017.09.007","article-title":"Progress toward Standardized Diagnosis of Vascular Cognitive Impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study","volume":"14","author":"Skrobot","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_36","first-page":"147","article-title":"Vascular Cognitive Impairment","volume":"25","year":"2019","journal-title":"Continuum"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1055\/s-0039-1678582","article-title":"Vascular Cognitive Disorder","volume":"39","author":"Paradise","year":"2019","journal-title":"Semin. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1002\/gps.5136","article-title":"Cognitive Screening Instruments to Identify Vascular Cognitive Impairment: A Systematic Review","volume":"34","author":"Ghafar","year":"2019","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1161\/STROKEAHA.115.010153","article-title":"First Ischemic Stroke in Sickle-Cell Disease: Are There any Adult Specificities?","volume":"46","author":"Calvet","year":"2015","journal-title":"Stroke"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1056\/NEJM199807023390102","article-title":"Prevention of a First Stroke by Transfusions in Children with Sickle Cell Anemia and Abnormal Results on Transcranial Doppler Ultrasonography","volume":"339","author":"Adams","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0022-3476(95)70204-0","article-title":"Risk of Recurrent Stroke in Patients with Sickle Cell Disease Treated with Erythrocyte Transfusions","volume":"126","author":"Pegelow","year":"1995","journal-title":"J. Pediatr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/jpepsy\/jsz100","article-title":"Correlates of Cognitive Function in Sickle Cell Disease: A Meta-Analysis","volume":"45","author":"Prussien","year":"2020","journal-title":"J. Pediatr. Psychol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"E841","DOI":"10.36076\/ppj.2015\/18\/E841","article-title":"Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter","volume":"18","author":"Ickmans","year":"2015","journal-title":"Pain Physician"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00431-015-2626-1","article-title":"The Impact of Chronic Fatigue Syndrome on Cognitive Functioning in Adolescents","volume":"175","author":"Nijhof","year":"2016","journal-title":"Eur. J. Pediatr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S0022-3999(02)00290-8","article-title":"Cognitive Functioning in Chronic Fatigue Syndrome and the Role of Depression, Anxiety, and Fatigue","volume":"52","author":"Short","year":"2002","journal-title":"J. Psychosom. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1615\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:39:43Z","timestamp":1760121583000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,17]]},"references-count":45,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jcm12041615"],"URL":"https:\/\/doi.org\/10.3390\/jcm12041615","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,17]]}}}