{ "abstract": "Background: Acetylcholinesterase inhibitors (AChEIs) provide symptomatic relief in Alzheimer’s disease (AD), whereas lecanemab may modify disease progression; however, real-world evidence on its safety and clinical impact remains limited. Therefore, this study aimed to compare the safety and effectiveness of initiating lecanemab versus AChEIs in patients with mild cognitive impairment (MCI) or AD.\n\nMethods: Using the TriNetX US electronic health record network, we conducted a retrospective cohort study including individuals diagnosed with MCI or AD between July 2023 and September 2025. A target trial emulation with 1:1 propensity score matching and Cox models estimated comparative risks.\n\nResults: Lecanemab was associated with a fivefold higher incidence of neuroimaging abnormalities than AChEIs, while 1-year treatment persistence was similar (53.4% vs 52.5%). After matching, 589 patients were included in each cohort. Compared with AChEIs, lecanemab was associated with significantly lower risks of behavioral and psychological symptoms of dementia (BPSD) (HR, 0.52; 95% CI, 0.36–0.77) and emergency visits (HR, 0.66; 95% CI, 0.51–0.85), but a higher risk of hospitalization (HR, 1.31; 95% CI, 1.03–1.67). Lecanemab was also associated with lower use of antipsychotics (HR, 0.47; 95% CI, 0.32–0.70), antidepressants (HR, 0.60; 95% CI, 0.43–0.85), melatonin/orexin antagonists (HR, 0.61; 95% CI, 0.42–0.88), antibiotics (HR, 0.61; 95% CI, 0.44–0.86), and antifungals (HR, 0.57; 95% CI, 0.37–0.88), whereas steroid use was higher among lecanemab users (HR, 2.19; 95% CI, 1.55–3.10).\n\nConclusions: Compared with an AChEI-based conventional care strategy, lecanemab initiation was associated with comparable treatment persistence and lower observed risks of BPSD, emergency visit as well as reduced use of psychotropic and infection-related medications in exploratory analyses. However, the higher incidence of neuroimaging abnormalities associated with lecanemab, along with increased risks of hospitalization and corticosteroid use, likely reflects proactive clinical monitoring and management of amyloid-related imaging abnormalities (ARIA). While residual confounding cannot be excluded and results warrant cautious interpretation, these exploratory findings warrant further validation in biomarker-confirmed cohorts and head-to-head randomized trials.\n\nGraphical Abstract:\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13195-026-02095-4.", "abstract_shown": true, "affiliations": [ "Department of Neurology, Mackay Memorial Hospital, Taipei, Taiwan", "Department of Medicine, Mackay Medical University, New Taipei City, Taiwan", "Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan", "Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan", "Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan", "Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan", "Institute of Precision Medicine, National Sun Yat-Sen University, Kaohsiung City, Taiwan", "Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan", "Department of Psychiatry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan", "Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK", "Centre for Chronic Illness and Ageing, University of Greenwich, London, UK", "IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC Australia", "Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan", "Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan", "Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan", "Department of Psychiatry, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan", "Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, No. 60, Xinmin Road, Beitou District, Taipei City, 112 Taiwan", "Department of Neurology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan", "Department of Psychiatry, E-DA Dachang Hospital, I-Shou University, No. 305, Dachang 1St Rd., Sanmin District, Kaohsiung City, 807 Taiwan", "Department of Psychiatry, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan", "School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan" ], "article_type": "research article", "arxiv": null, "author_total": 12, "authors": [ { "affs": [ 0, 1 ], "name": "Chuo-Yu Lee" }, { "affs": [ 2 ], "name": "Chih-Wei Hsu" }, { "affs": [ 3, 4, 5, 6 ], "name": "Ping-Tao Tseng" }, { "affs": [ 7, 8 ], "name": "Yi-Ya Fang" }, { "affs": [ 9 ], "name": "Brendon Stubbs" }, { "affs": [ 10 ], "name": "Trevor Thompson" }, { "affs": [ 11 ], "name": "Andre F. Carvalho" }, { "affs": [ 12, 13, 14 ], "name": "Yu-Hsuan Lin" }, { "affs": [ 15, 16 ], "name": "Yu-Chen Kao" }, { "affs": [ 17 ], "name": "Fu-Chi Yang" }, { "affs": [ 18, 19, 20 ], "name": "Tien-Wei Hsu", "orcid": "0000-0003-4136-1251" }, { "affs": [ 15, 16 ], "name": "Chih-Sung Liang", "orcid": "0000-0003-1138-5586" } ], "bibtex": "https://research.draconitic.com/paper/6040ttjsykjkk.bib", "cited_by": 0, "doi": "10.1186/s13195-026-02095-4", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711954/", "id": "6040ttjsykjkk", "issns": [ "1758-9193" ], "landing_url": "https://doi.org/10.1186/s13195-026-02095-4", "language": "en", "licence": "CC-BY-NC-ND-4.0", "licence_label": "CC BY-NC-ND 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Research" ], [ "openalex", "2737|Alzheimer's disease research and treatments" ] ], "openalex": "W7165571447", "pdf_url": null, "pmcid": "PMC13711954", "pmid": "42332768", "published": "2026-06-22", "publisher": "BMC", "ris": "https://research.draconitic.com/paper/6040ttjsykjkk.ris", "sources": [ { "first_seen": "2026-10-31T12:22:38Z", "native_id": "PMC13711954", "source": "pmc", "url": "https://doi.org/10.1186/s13195-026-02095-4" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2737|Alzheimer's disease research and treatments", "subfield": "physiology" } ], "title": "Real-world effectiveness of monoclonal antibody lecanemab versus acetylcholinesterase inhibitors in Alzheimer’s disease: a target trial emulation", "title_text": "Real-world effectiveness of monoclonal antibody lecanemab versus acetylcholinesterase inhibitors in Alzheimer’s disease: a target trial emulation", "type": "peer-reviewed", "updated_at": "2026-10-31T12:22:38Z", "url": "https://research.draconitic.com/paper/6040ttjsykjkk", "venue": "Alzheimer's Research & Therapy", "versions": [] }