{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:28:53Z","timestamp":1791322133300,"version":"4.3.1"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The outcome of levodopa\/carbidopa intestinal gel (LCIG) in Parkinson's disease carriers of <jats:italic>GBA1<\/jats:italic> mutations (GBA\u2010PD) remains uncertain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the safety and efficacy of LCIG in a large PD cohort, focusing on <jats:italic>GBA1<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This multicenter, retrospective, longitudinal \u201creal\u2010world\u201d study included consecutive patients with advanced PD treated with LCIG at 31 Italian centers; data were collected at baseline, 1\u2010, 5\u2010year, and last\u2010available follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Data from 512 PD patients (59% male, mean age and disease duration at LCIG initiation 67.0\u2009\u00b1\u20098.0 and 12.9\u2009\u00b1\u20095.0\u2009years, respectively) were analyzed. <jats:italic>GBA1<\/jats:italic> genotyping was available for 306 patients (60%), of whom 40 (13%) had <jats:italic>GBA1<\/jats:italic> mutations or risk variants. Mean follow\u2010up on LCIG was 3.9\u2009\u00b1\u20092.9\u2009years; 5\u2010year follow\u2010up data were available for 159 subjects. At baseline, GBA\u2010PD had a younger age, shorter PD duration, worse cognition, and more hallucinations than noncarriers. At 1\u2010 and 5\u2010year follow\u2010up, LCIG improved motor and non\u2010motor symptoms, OFF\u2010time, and dyskinesias in the entire population. In GBA\u2010PD, MDS\u2010UPDRS parts I, II, and III scores did not change, while part IV score improved significantly less than in noncarriers; cognition and orthostatic hypotension symptoms worsened more rapidly. Multivariate analysis of predictors for adverse events and LCIG discontinuation found no significant contribution from <jats:italic>GBA1<\/jats:italic> mutation status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>GBA1<\/jats:italic> status does not increase the risk of adverse events or LCIG discontinuation. LCIG is a safe option for advanced GBA\u2010PD, even in patients with cognitive impairment at baseline. However, GBA\u2010PD experiences lower efficacy on motor disability and complications and faster cognitive decline than noncarriers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.70179","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:14:47Z","timestamp":1752570887000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of <i>GBA1<\/i> Variants in Patients With Parkinson's Disease and Levodopa\u2013Carbidopa Intestinal Gel: A Nation\u2010Wide, Multicenter, Longitudinal, \u201cReal\u2010World\u201d Study. The <scp>EPIC<\/scp> Study"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1990-1939","authenticated-orcid":false,"given":"Roberto","family":"Cilia","sequence":"first","affiliation":[{"name":"Parkinson and Movement Disorders Unit, Department of Clinical Neurosciences Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Colucci","sequence":"additional","affiliation":[{"name":"Parkinson and Movement Disorders Unit, Department of Clinical Neurosciences Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"},{"name":"Azienda Ospedaliera Universitaria S. Anna U.O. Neurologia  Ferrara Italy"},{"name":"Department of Neuroscience and Rehabilitation University of Ferrara  Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0747-1951","authenticated-orcid":false,"given":"Emanuele","family":"Cereda","sequence":"additional","affiliation":[{"name":"Clinical Nutrition and Dietetics Unit Fondazione IRCCS Policlinico san Matteo  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio E.","family":"Elia","sequence":"additional","affiliation":[{"name":"Parkinson and Movement Disorders Unit, Department of Clinical Neurosciences Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Leta","sequence":"additional","affiliation":[{"name":"Parkinson and Movement Disorders Unit, Department of Clinical Neurosciences Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan 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