A case of chronic lymphocytic leukaemia with initial symptoms of cognitive impairment

A case of chronic lymphocytic leukaemia with initial symptoms of cognitive impairment | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A case of chronic lymphocytic leukaemia with initial symptoms of cognitive impairment Baoye Ye, Yilin Huang, Wanying Lai This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5849396/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Chronic lymphocytic leukaemia (CLL) is a type of leukaemia that is often ignored in the initial stages. Slight fever, fatigue and night sweats are common presentations, but cognitive decline is rare. Case presentation: A 69-year-old patient with early-stage CLL presented with rapid cognitive decline. The patient was taken by his wife to seek medical attention in our hospital. In his medical reports from other hospitals, the Mini-mental State Examination(MMSE) score was 10, and the Montreal Cognitive Assessment(MoCA) score was zero since he could not cooperate. MRI revealed bilateral hippocampal atrophy. The apolipoprotein E (APOE) gene test revealed that his genotype was e3/e4. A blood test also revealed high leucocyte and lymphocyte counts. Peripheral blood lymphocyte immunotyping was subsequently performed, and the results revealed abnormal monoclonal mature B cells. The final diagnosis was CLL. Discussion: To our knowledge, memory loss is rare in the primary phase of CLL. However, we linked this patient’s cognitive impairment with CLL. chronic lymphocytic leukaemia cognitive impairment initial symptoms Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Patients with CLL are usually older at diagnosis, and CLL is more prevalent in men than in women, indicating that the clinical course is highly variable[ 1 ]. CLL is characterized by large numbers of mature CD5+, CD10-, and small B lymphocytes with typical clonal proliferation and aggregation in the blood, bone marrow, lymph nodes and spleen[ 2 ]. A diagnosis of CLL requires ≥ 5000 clonal B lymphocytes/µL in the peripheral blood; CD5, CD19, and CD23 antigen expression; and light-chain surface immunoglobulin restriction confirmed by flow cytometry and lasting for at least three months[ 3 , 4 , 5 ]. The typical clinical presentation of CLL includes leukaemic involvement of the bone marrow, peripheral blood and lymphoid organs, which cause systemic symptoms such as fever, night sweats, fatigue and weight loss as the disease progresses[ 6 ]. CLL is the most common leukaemia in adults in the United States and Europe, with a lifetime risk of one in 175; however, symptomatic central nervous system involvement in CLL is extremely rare and is reported in less than 1% of CLL patients[ 1 , 7 ]. Here, we present a patient who initially presented with cognitive impairment and was finally diagnosed with CLL. Case description A 69-year-old man presented to our department with rapid cognitive decline for several months. His past medical history included diabetes mellitus type 2, and his most recent glycated haemoglobin level was 8.4%. The patient was diagnosed with severe cognitive impairment approximately 6 months prior, with a 10/30 score on the Mini-Mental State Examination (MMSE) and a 0/30 score on the Montreal Cognitive Assessment (MoCA). Magnetic resonance imaging (MRI) of the brain revealed bilateral inferior temporal lobe atrophy and widespread T2 hyperintensities throughout the frontal lobe, parietal lobe, temporal lobe, bilateral periventricular region, and brainstem. The apolipoprotein E (APOE) gene test revealed that his gene type was e3/e4 (Figure 1). His medical reports revealed an abnormal blood test result 6 months prior, namely, a leukocyte count of 20.69×10 9 /L and a lymphocyte count of 18.15×10 9 /L. Thyroid function, HIV, and RPR test results and serum vitamin C and folic acid levels were all normal. A complete blood count test was subsequently performed in our hospital, and the results were similar to those of the previous test, with a leukocyte count of 20.55×10 9 /L and a lymphocyte count of 16.66×10 9 /L. Peripheral blood immunophenotyping was subsequently performed by flow cytometric analysis. The results revealed a monoclonal B-lymphocyte population (82.2% lymphocytes, 78.9% abnormal monoclonal B lymphocytes)that was positive for CD45+, CD19, CD5, CD20, CD22, cCD79a, CD23, cKappa, CD200, and CD25 and negative for CD4, CD8, CD3, CD2, CD7, CD56, CD10, CD38, MPO, cCD3, FMC7, CD79b, cLambda, IGM, CD103, and CD11c. In summary, 60015 clonal B lymphocytes/µL were detected in the peripheral blood (Figure 2) in which CD5, CD19, and CD23 antigens were expressed (Figure 3) and the κ/λ ratio was abnormal (Figure 4). All of these results support a diagnosis of CLL. Discussion The diagnosis of cognitive impairment in this patient is accurate, and his memory loss was rapid. The APOE gene test and MRI results indicate that this patient is prone to developing Alzheimer's disease (AD). Previous studies indicate that the ɛ4 allele of the apolipoprotein E gene (APOE ɛ4) is the strongest genetic risk factor for AD[8,9,10]. The patient’s APOE genotype is e3/e4, which supports the diagnosis of AD. AD is a progressive neurological disorder characterized by cognitive decline, and typical AD symptoms begin slowly and worsen over time[11,12]. In this patient, the rapid deterioration of cognition suggests a more complicated situation. The patient underwent blood tests, MRI and APOE gene testing 6 months prior, but he did not attend a follow-up appointment. Therefore, we can only use the patient’s blood test results from 6 months prior. Our further examination results support the diagnosis of CLL. The medical history of the patient revealed that he had type 2 diabetes, but this condition did not necessarily lead to his rapid cognitive deterioration. The patient’s cognitive symptoms may be connected to CLL. We searched for a previous study to verify our theory. Cognitive impairment in chronic lymphocytic leukaemia patients is rare[13,14,15]. A previous study revealed that 36% of patients with CLL with cognitive decline had impaired immediate and delayed memory recall[13]. Memory loss was the most important symptom in this patient, and most of the evidence, including his age, MRI presentation, and APOE gene test results, supported the diagnosis of AD. The only evidence that did not support this diagnosis was the progress of the disease. The rapid decline in his cognition suggested a more complicated condition, and further testing indicated CLL. On the basis of his blood test results, we speculated that the duration of CLL was more than half a year. Although reports of cognitive impairment caused by CLL are rare, this patient’s CLL course indicates that his memory decline is related to CLL. Unfortunately, the patient refused further testing and treatment. Declarations The authors confirm that the wife of this patient (the legal guardian) has consented to participate and publish. Author Contribution Baoye Ye wrote the main manuscript text.Yilin Huang and Wanying Lai prepared figures 1-4.All authors teviewed the manuscript. References Webb LM, Kenderian SS, Angeli AM, Howard MT, Wijdicks EF. Chronic Lymphocytic Leukemia Infiltrating in the Brain. Cureus. 2024 Nov 20;16(11):e74080. doi: 10.7759/cureus.74080. PMID: 39712843; PMCID: PMC11660725. Burger JA.Treatment of chronic lymphocytic leukemia[J].N Engl J Med,2020,383(5):460-473. Wierda WG, Brown J, Abramson JS, Awan F, Bilgrami SF, Bociek G, Brander D, Cortese M, Cripe L, Davis RS, Eradat H, Fakhri B, Fletcher CD, Gaballa S, Hamid MS, Hill B, Kaesberg P, Kahl B, Kamdar M, Kipps TJ, Ma S, Mosse C, Nakhoda S, Parikh S, Schorr A, Schuster S, Seshadri M, Siddiqi T, Stephens DM, Thompson M, Ujjani C, Valdez R, Wagner-Johnston N, Woyach JA, Sundar H, Dwyer M. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024 Apr;22(3):175-204. doi: 10.6004/jnccn.2024.0018. PMID: 38626800. Robak T, Krawczyńska A, Cebula-Obrzut B, Urbaniak M, Iskierka-Jażdżewska E, Robak P. Atypical Chronic Lymphocytic Leukemia-The Current Status. Cancers (Basel). 2023 Sep 5;15(18):4427. doi: 10.3390/cancers15184427. PMID: 37760396; PMCID: PMC10527541. Hallek M, Al-Sawaf O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. Am J Hematol. 2021 Dec 1;96(12):1679-1705. doi: 10.1002/ajh.26367. PMID: 34625994. Ten Hacken E, Eichhorst B. Updates on the biology of chronic lymphocytic leukemia: introductory editorial. Semin Hematol. 2024 Jun;61(3):139-141. doi: 10.1053/j.seminhematol.2024.06.001. PMID: 38991818. Marzolini MAV, Jaunmuktane Z, Roddie C, O'Reilly M, Chiodini P, Peggs KS. Toxoplasmosis initially presenting as neurological sequelae of chimeric antigen receptor T-cell therapy. Lancet Infect Dis. 2019 Jul;19(7):788. doi: 10.1016/S1473-3099(19)30119-7. PMID: 31250826. Oveisgharan S, Yu L, de Paiva Lopes K, Tasaki S, Wang Y, Menon V, Schneider JA, Seyfried NT, Bennett DA. Proteins linking APOE ɛ4 with Alzheimer's disease. Alzheimers Dement. 2024 Jul;20(7):4499-4511. doi: 10.1002/alz.13867. Epub 2024 Jun 10. PMID: 38856164; PMCID: PMC11247662. Fortea J, Pegueroles J, Alcolea D, Belbin O, Dols-Icardo O, Vaqué-Alcázar L, Videla L, Gispert JD, Suárez-Calvet M, Johnson SC, Sperling R, Bejanin A, Lleó A, Montal V. APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease. Nat Med. 2024 May;30(5):1284-1291. doi: 10.1038/s41591-024-02931-w. Epub 2024 May 6. Erratum in: Nat Med. 2024 Jul;30(7):2093. doi: 10.1038/s41591-024-03127-y. PMID: 38710950. He K, Li B, Wang J, Wang Y, You Z, Chen X, Chen H, Li J, Huang Q, Guo Q, Huang YH, Guan Y, Chen K, Zhao J, Deng Y, Xie F. APOE ε4 is associated with decreased synaptic density in cognitively impaired participants. Alzheimers Dement. 2024 May;20(5):3157-3166. doi: 10.1002/alz.13775. Epub 2024 Mar 13. PMID: 38477490; PMCID: PMC11095422. Tenchov R, Sasso JM, Zhou QA. Alzheimer's Disease: Exploring the Landscape of Cognitive Decline. ACS Chem Neurosci. 2024 Nov 6;15(21):3800-3827. doi: 10.1021/acschemneuro.4c00339. Epub 2024 Oct 11. PMID: 39392435; PMCID: PMC11587518. Liu E, Zhang Y, Wang JZ. Updates in Alzheimer's disease: from basic research to diagnosis and therapies. Transl Neurodegener. 2024 Sep 4;13(1):45. doi: 10.1186/s40035-024-00432-x. PMID: 39232848; PMCID: PMC11373277. Williams AM, van Wijngaarden E, Seplaki CL, Heckler CE, Weber MT, Barr PM, Zent CS, Janelsins MC. Cognitive function in patients with chronic lymphocytic leukemia: a cross-sectional study examining effects of disease and treatment. Leuk Lymphoma. 2020 Jul;61(7):1627-1635. doi: 10.1080/10428194.2020.1728748. Epub 2020 Mar 9. PMID: 32148161; PMCID: PMC7384931. Dewaide R, Saevels K. Treatment strategy in chronic lymphocytic leukemia with symptomatic central nervous system involvement: A case report. Clin Case Rep. 2023 Nov 9;11(11):e7965. doi: 10.1002/ccr3.7965. PMID: 37953895; PMCID: PMC10636533. Williams AM, Zent CS, Janelsins MC. What is known and unknown about chemotherapy-related cognitive impairment in patients with haematological malignancies and areas of needed research. Br J Haematol. 2016 Sep;174(6):835-46. doi: 10.1111/bjh.14211. Epub 2016 Jul 8. PMID: 27391367; PMCID: PMC5626568. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5849396","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":403903393,"identity":"2ca38460-3e34-4310-9757-a642de90a677","order_by":0,"name":"Baoye Ye","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYBACAxDB2CAhJ8/e2PjwAwlaLIwNew43G0uQoKUiseFGepsADzFazNkPH5P4uEOCsXHmwzYGCQY7Od0GAlose9LSJGeekWBml05se1DAkGxsdoCQww7kmEnztkmwMc5ObDeQYDiQuI2glvNvzKT/tknwMNw8CCKJ0XIDaAtjm4QEww1GIrVYzniWbNl7RsLAsCcRGMgGRPjFnD/54I2fO+rq57Mff/jwQ4WdHEEtQMCCFIEGhJWDADNRyWQUjIJRMApGMAAAdvRDUQq5VCQAAAAASUVORK5CYII=","orcid":"","institution":"The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Baoye","middleName":"","lastName":"Ye","suffix":""},{"id":403903394,"identity":"fff1e281-cbd3-4561-919c-58c00beff7da","order_by":1,"name":"Yilin Huang","email":"","orcid":"","institution":"The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yilin","middleName":"","lastName":"Huang","suffix":""},{"id":403903395,"identity":"19da6572-e60a-4169-b61e-48ea0e09678a","order_by":2,"name":"Wanying Lai","email":"","orcid":"","institution":"The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Wanying","middleName":"","lastName":"Lai","suffix":""}],"badges":[],"createdAt":"2025-01-17 13:08:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5849396/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5849396/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74679724,"identity":"336ba95a-29d9-4599-8722-479e2f2ca62a","added_by":"auto","created_at":"2025-01-24 15:40:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":173899,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5849396/v1/364b1b30ac15de8d0aba5bf1.png"},{"id":74679723,"identity":"88a3d4a1-e66c-4800-9499-47fa5ad692f0","added_by":"auto","created_at":"2025-01-24 15:40:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":208610,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5849396/v1/ac4b0d2948b7887b1f4cccf1.png"},{"id":74680619,"identity":"645ca4f3-4930-4180-84ef-2a661c742c25","added_by":"auto","created_at":"2025-01-24 15:48:14","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":299734,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5849396/v1/e8556afb84f479ee9927de8e.png"},{"id":74679730,"identity":"0c841191-bf1e-4aa7-9da8-b1a6911d78af","added_by":"auto","created_at":"2025-01-24 15:40:14","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":162303,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5849396/v1/693aea2d71da6cf68a1994d1.png"},{"id":74681553,"identity":"320dfd1e-bc03-47eb-b852-968230e437ee","added_by":"auto","created_at":"2025-01-24 15:56:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1010848,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5849396/v1/0c5a8142-b105-44a1-8850-47dbe98cc553.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A case of chronic lymphocytic leukaemia with initial symptoms of cognitive impairment","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePatients with CLL are usually older at diagnosis, and CLL is more prevalent in men than in women, indicating that the clinical course is highly variable[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. CLL is characterized by large numbers of mature CD5+, CD10-, and small B lymphocytes with typical clonal proliferation and aggregation in the blood, bone marrow, lymph nodes and spleen[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. A diagnosis of CLL requires\u0026thinsp;\u0026ge;\u0026thinsp;5000 clonal B lymphocytes/\u0026micro;L in the peripheral blood; CD5, CD19, and CD23 antigen expression; and light-chain surface immunoglobulin restriction confirmed by flow cytometry and lasting for at least three months[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The typical clinical presentation of CLL includes leukaemic involvement of the bone marrow, peripheral blood and lymphoid organs, which cause systemic symptoms such as fever, night sweats, fatigue and weight loss as the disease progresses[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCLL is the most common leukaemia in adults in the United States and Europe, with a lifetime risk of one in 175; however, symptomatic central nervous system involvement in CLL is extremely rare and is reported in less than 1% of CLL patients[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Here, we present a patient who initially presented with cognitive impairment and was finally diagnosed with CLL.\u003c/p\u003e"},{"header":"Case description","content":"\u003cp\u003eA 69-year-old man presented to our department with rapid cognitive decline for several months. His past medical history included diabetes mellitus type 2, and his most recent glycated haemoglobin level was 8.4%. The patient\u0026nbsp;was diagnosed with severe cognitive impairment approximately 6 months prior, with a 10/30 score on the Mini-Mental State Examination (MMSE) and a 0/30 score on the Montreal Cognitive Assessment (MoCA). Magnetic resonance imaging (MRI) of the brain revealed bilateral inferior temporal lobe atrophy and widespread T2 hyperintensities throughout the frontal lobe, parietal lobe, temporal lobe, bilateral periventricular region, and brainstem. The apolipoprotein E (APOE) gene test revealed that his gene type was e3/e4 (Figure 1).\u003c/p\u003e\n\u003cp\u003eHis medical reports revealed an abnormal blood test result 6 months prior, namely, a leukocyte count of 20.69\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L and a lymphocyte count of 18.15\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L.\u0026nbsp;Thyroid function, HIV, and RPR test results and serum vitamin C and folic acid levels were all normal. A complete blood count test was subsequently performed in our hospital, and the results were similar to those of the previous test, with a leukocyte count of 20.55\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L and a lymphocyte count of 16.66\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L. Peripheral blood immunophenotyping was subsequently performed by flow cytometric analysis. The results revealed a monoclonal B-lymphocyte population (82.2% lymphocytes, 78.9% abnormal monoclonal B lymphocytes)that was positive for CD45+, CD19, CD5, CD20, CD22, cCD79a, CD23, cKappa, CD200, and CD25 and negative for CD4, CD8, CD3, CD2, CD7, CD56, CD10, CD38, MPO, cCD3, FMC7, CD79b, cLambda, IGM, CD103, and CD11c.\u003c/p\u003e\n\u003cp\u003eIn summary, 60015 clonal B lymphocytes/\u0026micro;L were detected in the peripheral blood (Figure 2) in which CD5, CD19, and CD23 antigens were expressed (Figure 3) and the \u0026kappa;/\u0026lambda; ratio was abnormal (Figure 4). All of these results support a diagnosis of CLL.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe diagnosis of cognitive impairment in this patient is accurate, and his memory loss was rapid. The APOE gene test and MRI results indicate that this patient is prone to developing Alzheimer's disease (AD). Previous studies indicate that the ɛ4 allele of the apolipoprotein E gene (APOE ɛ4) is the strongest genetic risk factor for AD[8,9,10]. The patient’s APOE genotype is e3/e4, which supports the diagnosis of AD. AD is a progressive neurological disorder characterized by cognitive decline, and typical AD symptoms begin slowly and worsen over time[11,12]. In this patient, the rapid deterioration of cognition suggests a more complicated situation.\u003c/p\u003e\n\u003cp\u003eThe patient underwent blood tests, MRI and APOE gene testing 6 months prior, but he did not attend a follow-up appointment. Therefore, we can only use the patient’s blood test results from 6 months prior. Our further examination results support the diagnosis of CLL. The medical history of the patient revealed that he had type 2 diabetes, but this condition did not necessarily lead to his rapid cognitive deterioration. The patient’s cognitive symptoms may be connected to CLL. We searched for a previous study to verify our theory. Cognitive impairment in chronic lymphocytic leukaemia patients is rare[13,14,15]. A previous study revealed that 36% of patients with CLL with cognitive decline had impaired immediate and delayed memory recall[13].\u003c/p\u003e\n\u003cp\u003eMemory loss was the most important symptom in this patient, and most of the evidence, including his age, MRI presentation, and APOE gene test results, supported the diagnosis of AD. The only evidence that did not support this diagnosis was the progress of the disease. The rapid decline in his cognition suggested a more complicated condition,\u0026nbsp;and further testing indicated CLL. On the basis of his blood test results, we speculated that the duration of CLL was more than half a year. Although reports of cognitive impairment caused by CLL are rare, this patient’s CLL course indicates that his memory decline is related to CLL. Unfortunately, the patient refused further testing and treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors confirm that the wife of this patient (the legal guardian) has consented to participate and publish.\u003c/p\u003e\n\u003cp\u003eAuthor Contribution\u003c/p\u003e\n\u003cp\u003eBaoye Ye wrote the main manuscript text.Yilin Huang and Wanying Lai prepared figures 1-4.All authors teviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWebb LM, Kenderian SS, Angeli AM, Howard MT, Wijdicks EF. Chronic Lymphocytic Leukemia Infiltrating in the Brain. Cureus. 2024 Nov 20;16(11):e74080. doi: 10.7759/cureus.74080. PMID: 39712843; PMCID: PMC11660725.\u003c/li\u003e\n\u003cli\u003eBurger JA.Treatment of chronic lymphocytic leukemia[J].N Engl J Med,2020,383(5):460-473.\u003c/li\u003e\n\u003cli\u003eWierda WG, Brown J, Abramson JS, Awan F, Bilgrami SF, Bociek G, Brander D, Cortese M, Cripe L, Davis RS, Eradat H, Fakhri B, Fletcher CD, Gaballa S, Hamid MS, Hill B, Kaesberg P, Kahl B, Kamdar M, Kipps TJ, Ma S, Mosse C, Nakhoda S, Parikh S, Schorr A, Schuster S, Seshadri M, Siddiqi T, Stephens DM, Thompson M, Ujjani C, Valdez R, Wagner-Johnston N, Woyach JA, Sundar H, Dwyer M. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024 Apr;22(3):175-204. doi: 10.6004/jnccn.2024.0018. PMID: 38626800.\u003c/li\u003e\n\u003cli\u003eRobak T, Krawczyńska A, Cebula-Obrzut B, Urbaniak M, Iskierka-Jażdżewska E, Robak P. Atypical Chronic Lymphocytic Leukemia-The Current Status. Cancers (Basel). 2023 Sep 5;15(18):4427. doi: 10.3390/cancers15184427. PMID: 37760396; PMCID: PMC10527541.\u003c/li\u003e\n\u003cli\u003eHallek M, Al-Sawaf O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. Am J Hematol. 2021 Dec 1;96(12):1679-1705. doi: 10.1002/ajh.26367. PMID: 34625994.\u003c/li\u003e\n\u003cli\u003eTen Hacken E, Eichhorst B. Updates on the biology of chronic lymphocytic leukemia: introductory editorial. Semin Hematol. 2024 Jun;61(3):139-141. doi: 10.1053/j.seminhematol.2024.06.001. PMID: 38991818.\u003c/li\u003e\n\u003cli\u003eMarzolini MAV, Jaunmuktane Z, Roddie C, O\u0026apos;Reilly M, Chiodini P, Peggs KS. Toxoplasmosis initially presenting as neurological sequelae of chimeric antigen receptor T-cell therapy. Lancet Infect Dis. 2019 Jul;19(7):788. doi: 10.1016/S1473-3099(19)30119-7. PMID: 31250826.\u003c/li\u003e\n\u003cli\u003eOveisgharan S, Yu L, de Paiva Lopes K, Tasaki S, Wang Y, Menon V, Schneider JA, Seyfried NT, Bennett DA. Proteins linking APOE ɛ4 with Alzheimer\u0026apos;s disease. Alzheimers Dement. 2024 Jul;20(7):4499-4511. doi: 10.1002/alz.13867. Epub 2024 Jun 10. PMID: 38856164; PMCID: PMC11247662.\u003c/li\u003e\n\u003cli\u003eFortea J, Pegueroles J, Alcolea D, Belbin O, Dols-Icardo O, Vaqu\u0026eacute;-Alc\u0026aacute;zar L, Videla L, Gispert JD, Su\u0026aacute;rez-Calvet M, Johnson SC, Sperling R, Bejanin A, Lle\u0026oacute; A, Montal V. APOE4 homozygozity represents a distinct genetic form of Alzheimer\u0026apos;s disease. Nat Med. 2024 May;30(5):1284-1291. doi: 10.1038/s41591-024-02931-w. Epub 2024 May 6. Erratum in: Nat Med. 2024 Jul;30(7):2093. doi: 10.1038/s41591-024-03127-y. PMID: 38710950.\u003c/li\u003e\n\u003cli\u003eHe K, Li B, Wang J, Wang Y, You Z, Chen X, Chen H, Li J, Huang Q, Guo Q, Huang YH, Guan Y, Chen K, Zhao J, Deng Y, Xie F. 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Cognitive function in patients with chronic lymphocytic leukemia: a cross-sectional study examining effects of disease and treatment. Leuk Lymphoma. 2020 Jul;61(7):1627-1635. doi: 10.1080/10428194.2020.1728748. Epub 2020 Mar 9. PMID: 32148161; PMCID: PMC7384931.\u003c/li\u003e\n\u003cli\u003eDewaide R, Saevels K. Treatment strategy in chronic lymphocytic leukemia with symptomatic central nervous system involvement: A case report. Clin Case Rep. 2023 Nov 9;11(11):e7965. doi: 10.1002/ccr3.7965. PMID: 37953895; PMCID: PMC10636533.\u003c/li\u003e\n\u003cli\u003eWilliams AM, Zent CS, Janelsins MC. What is known and unknown about chemotherapy-related cognitive impairment in patients with haematological malignancies and areas of needed research. Br J Haematol. 2016 Sep;174(6):835-46. doi: 10.1111/bjh.14211. Epub 2016 Jul 8. PMID: 27391367; PMCID: PMC5626568.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"chronic lymphocytic leukaemia, cognitive impairment, initial symptoms","lastPublishedDoi":"10.21203/rs.3.rs-5849396/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5849396/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Chronic lymphocytic leukaemia (CLL) is a type of leukaemia that is often ignored in the initial stages. Slight fever, fatigue and night sweats are common presentations, but cognitive decline is rare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e A 69-year-old patient with early-stage CLL presented with rapid cognitive decline. The patient was taken by his wife to seek medical attention in our hospital. In his medical reports from other hospitals, the Mini-mental State Examination(MMSE) score was 10, and the Montreal Cognitive Assessment(MoCA) score was zero since he could not cooperate. MRI revealed bilateral hippocampal atrophy. The apolipoprotein E (APOE) gene test revealed that his genotype was e3/e4. A blood test also revealed high leucocyte and lymphocyte counts. Peripheral blood lymphocyte immunotyping was subsequently performed, and the results revealed abnormal monoclonal mature B cells. The final diagnosis was CLL.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion: \u003c/strong\u003eTo our knowledge, memory loss is rare in the primary phase of CLL. However, we linked this patient’s cognitive impairment with CLL.\u003c/p\u003e","manuscriptTitle":"A case of chronic lymphocytic leukaemia with initial symptoms of cognitive impairment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-24 15:40:09","doi":"10.21203/rs.3.rs-5849396/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6a38879f-4136-41ae-8641-a912a85a61c4","owner":[],"postedDate":"January 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-18T12:23:38+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-24 15:40:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5849396","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5849396","identity":"rs-5849396","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}