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To delineate trajectories of motor and non-motor markers as well as serum neurofilament light (sNfL) levels and to evaluate clinical endpoints as outcomes for clinical trials in GBA1\n                    <jats:sub>NMC<\/jats:sub>\n                    , longitudinal data of 56 GBA1\n                    <jats:sub>NMC<\/jats:sub>\n                    carriers and 112 age- and sex-matched\n                    <jats:italic>GBA1<\/jats:italic>\n                    wildtype participants (GBA1\n                    <jats:sub>wildtype<\/jats:sub>\n                    ) with up to 9 years of follow-up was analyzed using linear mixed-effects models (LMEM) and Kaplan\u2013Meier survival analysis of clinical endpoints for motor and cognitive function. GBA1\n                    <jats:sub>NMC<\/jats:sub>\n                    showed worse performance in Pegboard, 20\u2009m fast walking, global cognition as well as in executive and memory function at baseline. Longitudinally, LMEM revealed a higher annual increase of the MDS-UPDRS III bradykinesia subscore in GBA1\n                    <jats:sub>NMC<\/jats:sub>\n                    compared to GBA1\n                    <jats:sub>wildtype<\/jats:sub>\n                    , but comparable trajectories of all other motor and non-motor markers as well as sNfL. Kaplan\u2013Meier survival analysis showed a significantly earlier progression to clinical endpoints of cognitive decline in GBA1\n                    <jats:sub>NMC<\/jats:sub>\n                    . Incidence of PD was significantly higher in GBA1\n                    <jats:sub>NMC<\/jats:sub>\n                    . In conclusion, our study extends data on GBA1\n                    <jats:sub>NMC<\/jats:sub>\n                    indicating early cognitive decline as a potentially characteristic feature. Comprehensive longitudinal assessments of cognitive function are crucial to delineate the evolution of early changes in GBA1\n                    <jats:sub>NMC<\/jats:sub>\n                    enabling a more accurate stratification and allow for a more precise definition of trial design and sample size.\n                  <\/jats:p>","DOI":"10.1038\/s41531-024-00706-1","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T04:02:05Z","timestamp":1713758525000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Longitudinal cognitive decline characterizes the profile of non-PD-manifest GBA1 mutation carriers"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4905-8698","authenticated-orcid":false,"given":"Benjamin","family":"Roeben","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0875-892X","authenticated-orcid":false,"given":"Inga","family":"Liepelt-Scarfone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5508-004X","authenticated-orcid":false,"given":"Stefanie","family":"Lerche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7066-7749","authenticated-orcid":false,"given":"Milan","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Wurster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5348-3996","authenticated-orcid":false,"given":"Ulrike","family":"S\u00fcnkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Schulte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Deuschle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard W.","family":"Eschweiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5945-4694","authenticated-orcid":false,"given":"Walter","family":"Maetzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1069-1146","authenticated-orcid":false,"given":"Thomas","family":"Gasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-8596","authenticated-orcid":false,"given":"Kathrin","family":"Brockmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"706_CR1","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1002\/mds.26431","volume":"30","author":"D Berg","year":"2015","unstructured":"Berg, D. et al. 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I.L.S. has received grants from Janssen Research and Development, a division of Janssen Pharmaceutica N.V. and grants from the Michael J. Fox Foundation; grants from European Commission, H2020-TWINN-2015, International Parkinson Fonds (Deutschland) GmbH (IPD), Novartis and German Ministry for Education and Research (BMBF). S.L. has nothing to disclose. M.Z. was supported by the Clinician Scientist program of the Medical Faculty of the University of T\u00fcbingen (grant #481-0-0). I.W. received funding from the Michael J. Fox Foundation in form of the Edmond J. Safra Fellowship in Movement Disorders. C.S. has nothing to report. C.D. has nothing to report. G.W.E. has received grants from the German Federal Ministry of Education of Research (BMBF), German Research Council (DFG), German Innovationsfonds but not from industrial partners. W.M. receives or received funding from the European Union, the German Federal Ministry of Education of Research, German Research Council, Michael J. Fox Foundation, Robert Bosch Foundation, Neuroalliance, Lundbeck, Sivantos and Janssen. He received speaker honoraria from Abbvie, Bayer, BIAL, GlaxoSmithKline, Heel, Licher MT, Pfizer, Takeda and UCB, was invited to Advisory Boards\/Consultancies of Abbvie, Aptar Digital Health, Atheneum, Biogen, Kyowa Kirin, Lundbeck and Market Access & Pricing Strategy GmbH, is an advisory board member of the Critical Path for Parkinson\u2019s Consortium, and an editorial board member of Geriatric Care. He serves as the co-chair of the MDS Technology Working Group. T.G. serves as associate editor at Journal of Parkinson\u2019s disease; holds a patent re: KASPP (LRRK2) Gene, its Production and Use for the Detection and Treatment of Neurodegenerative Diseases; serves as a consultant for Cephalon, Inc. and Merck Serono; serves on speaker\u2019s bureaus of Novartis, Merck Serono, SCHWARZ PHARMA, Boehringer Ingelheim, and Valeant Pharmaceuticals International; and receives research support from Novartis, the European Union, BMBF (the Federal Ministry of Education and Research), and Helmholtz Association. D.B. has served on scientific advisory boards for UCB\/ SCHWARZ PHARMA, Lundbeck, Biogen and BIAL.; has received funding for travel or speaker honoraria from Lundbeck Inc., Novartis, UCB\/ SCHWARZ PHARMA, Merck Serono, Biogen, Zambon, AbbVie, and BIALLtd.; and has received research support from Janssen, Teva Pharmaceutical Industries Ltd., Solvay Pharmaceuticals, Inc.\/Abbott, Boehringer, UCB, Michael J Fox Foundation, BMBF, dPV (German Parkinson\u2019s disease association), Neuroallianz, DZNE,Center of Integrative Neurosciences and the Damp Foundation. K.B. has received research grants from the University of Tuebingen (Clinician Scientist), the German Society of Parkinson\u2019s disease (dpv), the Michael J. Fox Foundation (MJFF), the German Centre for Neurodegenerative Diseases (DZNE, MIGAP) and the German Federal Ministry of Education and Research (BMBF) in the frame of ERACoSysMed2 (FKZ 031L0137B). She received Speaker honoraria from Abbvie, Lundbeck, UCB and Zambon. She serves as consultant for Roche.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"88"}}