{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:10:55Z","timestamp":1784099455061,"version":"3.55.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"PNRR","award":["PNRR-MAD-2022-12376496"],"award-info":[{"award-number":["PNRR-MAD-2022-12376496"]}]},{"DOI":"10.13039\/501100006692","name":"Universit\u00e0 degli Studi di Torino","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Age at onset is a key determinant of disease course in the general Parkinson\u2019s disease (PD) population, but its influence among GBA-PD remains undetermined. This study investigates whether age at onset affects cognitive decline in GBA-PD patients and compares symptoms between GBA-PD and nonGBA-PD groups, stratified by age of onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this multicentric cross-sectional study, PD patients were stratified into early onset (&lt;\u200950\u00a0years), intermediate onset (50\u201360\u00a0years), and late onset (&gt;\u200960\u00a0years). Demographic\u2013clinical data and scores of the Movement Disorder Society\u2014Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson\u2019s Disease\u2014Autonomic Dysfunction (SCOPA-AUT), and Beck Depression Inventory (BDI-II) were compared using ANCOVA. The effects of age of onset,\n                      <jats:italic>GBA1<\/jats:italic>\n                      status, and their interaction were investigated. External validation on cognition was performed using data from the PPMI cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We analyzed 80 GBA-PD and 236 nonGBA-PD patients. Among GBA-PD, late-onset patients exhibited worse axial scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.037), while early-onset had more severe motor complications (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007) and dysautonomia (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.012). Age of onset and\n                      <jats:italic>GBA1<\/jats:italic>\n                      status did not influence MoCA scores. Conversely,\n                      <jats:italic>GBA1<\/jats:italic>\n                      status independently affected MDS-UPDRS parts I and II (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.019, respectively) and BDI-II scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Analysis on the external dataset (PPMI) showed late-onset PD had lower MoCA scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and confirmed\n                      <jats:italic>GBA1<\/jats:italic>\n                      status did not influence cognition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      In the first decade of PD, cognitive decline is mainly age and duration dependent, irrespective of\n                      <jats:italic>GBA1<\/jats:italic>\n                      genotype. Early onset does not increase cognitive risk in GBA-PD, supporting its relevance for counseling and treatment planning.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13639-x","type":"journal-article","created":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T08:36:54Z","timestamp":1769935014000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The interplay between GBA1 status and age of onset on cognitive, motor and non-motor outcomes in Parkinson\u2019s disease: multicenter cross-sectional study"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0839-932X","authenticated-orcid":false,"given":"Claudia","family":"Ledda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micol","family":"Avenali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo Alberto","family":"Artusi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Imbalzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Donetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Montanaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Romagnolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierfrancesco","family":"Mitrotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"De Micco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Sant\u2019Elia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Siciliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Tessitore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Calandra-Buonaura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Giannini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Sambati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Lopiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enza Maria","family":"Valente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Bozzali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"issue":"5","key":"13639_CR1","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1002\/ana.24777","volume":"80","author":"R Cilia","year":"2016","unstructured":"Cilia R, Tunesi S, Marotta G et al (2016) Survival and dementia in GBA-associated Parkinson\u2019s disease: the mutation matters. Ann Neurol 80(5):662\u2013673. https:\/\/doi.org\/10.1002\/ana.24777","journal-title":"Ann Neurol"},{"key":"13639_CR2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.694764","volume":"12","author":"E Menozzi","year":"2021","unstructured":"Menozzi E, Schapira AHV (2021) Exploring the genotype-phenotype correlation in\u00a0GBA-Parkinson disease: clinical aspects, biomarkers, and potential modifiers. Front Neurol 12:694764. https:\/\/doi.org\/10.3389\/fneur.2021.694764","journal-title":"Front Neurol"},{"issue":"11","key":"13639_CR3","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1002\/mds.28195","volume":"35","author":"S Petrucci","year":"2020","unstructured":"Petrucci S, Ginevrino M, Trezzi I et al (2020) GBA-related Parkinson\u2019s disease: dissection of genotype-phenotype correlates in a large Italian cohort. Mov Disord 35(11):2106\u20132111. https:\/\/doi.org\/10.1002\/mds.28195","journal-title":"Mov Disord"},{"issue":"8","key":"13639_CR4","doi-asserted-by":"publisher","DOI":"10.3390\/cells11081261","volume":"11","author":"L Smith","year":"2022","unstructured":"Smith L, Schapira AHV (2022) GBA\u00a0variants and Parkinson disease: mechanisms and treatments. Cells 11(8):1261. https:\/\/doi.org\/10.3390\/cells11081261","journal-title":"Cells"},{"key":"13639_CR5","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1056\/NEJMoa0901281","volume":"361","author":"E Sidransky","year":"2009","unstructured":"Sidransky E, Nalls MA, Aasly JO et al (2009) Multicenter analysis of glucocerebrosidase mutations in Parkinson\u2019s disease. N Engl J Med 361:1651\u20131661. https:\/\/doi.org\/10.1056\/NEJMoa0901281","journal-title":"N Engl J Med"},{"key":"13639_CR6","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1002\/ana.24781","volume":"80","author":"G Liu","year":"2016","unstructured":"Liu G, Boot B, Locascio JJ et al (2016) Specifically neuropathic Gaucher\u2019s mutations accelerate cognitive decline in Parkinson\u2019s. Ann Neurol 80:674\u2013685. https:\/\/doi.org\/10.1002\/ana.24781","journal-title":"Ann Neurol"},{"issue":"2","key":"13639_CR7","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14387","volume":"30","author":"J Ren","year":"2024","unstructured":"Ren J, Zhan X, Zhou H et al (2024) Comparing the effects of GBA variants and onset age on clinical features and progression in Parkinson\u2019s disease. CNS Neurosci Ther 30(2):e14387. https:\/\/doi.org\/10.1111\/cns.14387","journal-title":"CNS Neurosci Ther"},{"issue":"6","key":"13639_CR8","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1007\/s10072-021-05230-1","volume":"42","author":"Q Li","year":"2021","unstructured":"Li Q, Jing Y, Lun P, Liu X, Sun P (2021) Association of gender and age at onset with glucocerebrosidase associated Parkinson\u2019s disease: a systematic review and meta-analysis. Neurol Sci 42(6):2261\u20132271. https:\/\/doi.org\/10.1007\/s10072-021-05230-1","journal-title":"Neurol Sci"},{"issue":"7","key":"13639_CR9","doi-asserted-by":"publisher","first-page":"e1036","DOI":"10.1212\/WNL.0000000000011411","volume":"96","author":"J Maple-Gr\u00f8dem","year":"2021","unstructured":"Maple-Gr\u00f8dem J, Dalen I, Tysnes OB et al (2021) Association of GBA genotype with motor and functional decline in patients with newly diagnosed Parkinson disease. Neurology 96(7):e1036\u2013e1044. https:\/\/doi.org\/10.1212\/WNL.0000000000011411","journal-title":"Neurology"},{"issue":"1","key":"13639_CR10","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/mdc3.12229","volume":"3","author":"G Pal","year":"2015","unstructured":"Pal G, Robertson E, O\u2019Keefe J, Hall D (2015) The neuropsychiatric and motor profile of GBA-associated Parkinson\u2019s disease: a review. Mov Disord Clin Pract 3(1):4\u20138. https:\/\/doi.org\/10.1002\/mdc3.12229","journal-title":"Mov Disord Clin Pract"},{"issue":"3","key":"13639_CR11","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1212\/WNL.0b013e318225ab77","volume":"77","author":"K Brockmann","year":"2011","unstructured":"Brockmann K, Srulijes K, Hauser AK et al (2011) GBA-associated PD presents with nonmotor characteristics. Neurology 77(3):276\u2013280. https:\/\/doi.org\/10.1212\/WNL.0b013e318225ab77","journal-title":"Neurology"},{"issue":"3","key":"13639_CR12","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1002\/ana.26302","volume":"91","author":"G Pal","year":"2022","unstructured":"Pal G, Mangone G, Hill EJ, Ouyang B et al (2022) Parkinson disease and subthalamic nucleus deep brain stimulation: cognitive effects in GBA mutation carriers. Ann Neurol 91(3):424\u2013435. https:\/\/doi.org\/10.1002\/ana.26302","journal-title":"Ann Neurol"},{"key":"13639_CR13","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.parkreldis.2020.04.002","volume":"76","author":"G Mangone","year":"2020","unstructured":"Mangone G, Bekadar S, Cormier-Dequaire F et al (2020) Early cognitive decline after bilateral subthalamic deep brain stimulation in Parkinson\u2019s disease patients with GBA mutations. Parkinsonism Relat Disord 76:56\u201362. https:\/\/doi.org\/10.1016\/j.parkreldis.2020.04.002","journal-title":"Parkinsonism Relat Disord"},{"issue":"4","key":"13639_CR14","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1136\/jnnp-2023-332387","volume":"95","author":"M Avenali","year":"2024","unstructured":"Avenali M, Zangaglia R, Cuconato G et al (2024) Are patients with GBA-Parkinson disease good candidates for deep brain stimulation? A longitudinal multicentric study on a large Italian cohort. J Neurol Neurosurg Psychiatry 95(4):309\u2013315. https:\/\/doi.org\/10.1136\/jnnp-2023-332387","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"13639_CR15","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2018.7800","volume":"2","author":"CA Artusi","year":"2019","unstructured":"Artusi CA, Dwivedi AK, Romagnolo A et al (2019) Association of sub- thalamic deep brain stimulation with motor, functional, and pharmacologic outcomes in patients with monogenic Parkinson disease: a systematic review and meta-analysis. JAMA Netw Open 2:e187800. https:\/\/doi.org\/10.1001\/jamanetworkopen.2018.7800","journal-title":"JAMA Netw Open"},{"key":"13639_CR16","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1212\/WNL.0b013e3181f61311","volume":"75","author":"EB Forsaa","year":"2010","unstructured":"Forsaa EB, Larsen JP, Wentzel-Larsen T, Alves G (2010) What predicts mortality in Parkinson disease?: a prospective population-based long-term study. Neurology 75:1270\u20131276. https:\/\/doi.org\/10.1212\/WNL.0b013e3181f61311","journal-title":"Neurology"},{"issue":"4","key":"13639_CR17","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/S1474-4422(06)70411-2","volume":"5","author":"A Schrag","year":"2006","unstructured":"Schrag A, Schott JM (2006) Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism. Lancet Neurol 5(4):355\u2013363. https:\/\/doi.org\/10.1016\/S1474-4422(06)70411-2","journal-title":"Lancet Neurol"},{"issue":"4","key":"13639_CR18","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1111\/j.1468-1331.2008.02514.x","volume":"16","author":"MM Wickremaratchi","year":"2009","unstructured":"Wickremaratchi MM, Ben-Shlomo Y, Morris HR (2009) The effect of onset age on the clinical features of Parkinson\u2019s disease. Eur J Neurol 16(4):450\u2013456. https:\/\/doi.org\/10.1111\/j.1468-1331.2008.02514.x","journal-title":"Eur J Neurol"},{"issue":"15","key":"13639_CR19","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1212\/WNL.0000000000002461","volume":"86","author":"G Pagano","year":"2016","unstructured":"Pagano G, Ferrara N, Brooks DJ, Pavese N (2016) Age at onset and Parkinson disease phenotype. Neurology 86(15):1400\u20131407. https:\/\/doi.org\/10.1212\/WNL.0000000000002461","journal-title":"Neurology"},{"issue":"9596","key":"13639_CR20","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","volume":"370","author":"E von Elm","year":"2007","unstructured":"von Elm E, Altman DG, Egger M, Pocock SJ, G\u00f8tzsche PC, Vandenbroucke JP (2007) The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370(9596):1453\u20131457. https:\/\/doi.org\/10.1016\/S0140-6736(07)61602-X","journal-title":"Lancet"},{"key":"13639_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2025.107780","author":"G Cuconato","year":"2025","unstructured":"Cuconato G, Palmieri I, Percetti M et al (2025) LONG-NEXT: a new accurate and efficient NGS-based method for GBA1 analysis in Parkinson disease. Parkinsonism Relat Disord. https:\/\/doi.org\/10.1016\/j.parkreldis.2025.107780","journal-title":"Parkinsonism Relat Disord"},{"issue":"12","key":"13639_CR22","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","volume":"30","author":"RB Postuma","year":"2015","unstructured":"Postuma RB, Berg D, Stern M et al (2015) MDS clinical diagnostic criteria for Parkinson\u2019s disease. Mov Disord 30(12):1591\u20131601. https:\/\/doi.org\/10.1002\/mds.26424","journal-title":"Mov Disord"},{"issue":"7","key":"13639_CR23","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1002\/mds.29410","volume":"38","author":"ST Jost","year":"2023","unstructured":"Jost ST, Kaldenbach MA, Antonini A et al (2023) Levodopa dose equivalency in Parkinson\u2019s disease: updated systematic review and proposals. Mov Disord 38(7):1236\u20131252. https:\/\/doi.org\/10.1002\/mds.29410","journal-title":"Mov Disord"},{"issue":"15","key":"13639_CR24","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1002\/mds.22340","volume":"23","author":"CG Goetz","year":"2008","unstructured":"Goetz CG, Tilley BC, Shaftman SR et al (2008) Movement disorder society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23(15):2129\u20132170. https:\/\/doi.org\/10.1002\/mds.22340","journal-title":"Mov Disord"},{"issue":"1","key":"13639_CR25","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1111\/ene.15558","volume":"30","author":"G Imbalzano","year":"2023","unstructured":"Imbalzano G, Rinaldi D, Calandra-Buonaura G et al (2023) How resistant are levodopa-resistant axial symptoms? Response of freezing, posture, and voice to increasing levodopa intestinal infusion rates in Parkinson disease. Eur J Neurol 30(1):96\u2013106. https:\/\/doi.org\/10.1111\/ene.15558","journal-title":"Eur J Neurol"},{"issue":"9","key":"13639_CR26","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1111\/jgs.15925","volume":"67","author":"ZS Nasreddine","year":"2019","unstructured":"Nasreddine ZS, Phillips NA, B\u00e9dirian V et al (2019) The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 67(9):1991. https:\/\/doi.org\/10.1111\/jgs.15925","journal-title":"J Am Geriatr Soc"},{"issue":"11","key":"13639_CR27","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1002\/mds.20153","volume":"19","author":"M Visser","year":"2004","unstructured":"Visser M, Marinus J, Stiggelbout AM, Van Hilten JJ (2004) Assessment of autonomic dysfunction in Parkinson\u2019s disease: the SCOPA-AUT. Mov Disord 19(11):1306\u20131312. https:\/\/doi.org\/10.1002\/mds.20153","journal-title":"Mov Disord"},{"key":"13639_CR28","volume-title":"BDI-II: beck depression inventory manual","author":"AT Beck","year":"1996","unstructured":"Beck AT, Steer RA, Brown GK (1996) BDI-II: beck depression inventory manual, 2nd edn. Psychological Corporation, San Antonio","edition":"2"},{"issue":"7","key":"13639_CR29","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1002\/mdc3.13523","volume":"9","author":"R Mehanna","year":"2022","unstructured":"Mehanna R, Smilowska K, Fleisher J et al (2022) Age cutoff for early-onset Parkinson\u2019s disease: recommendations from the International Parkinson and Movement Disorder Society Task Force on Early Onset Parkinson\u2019s Disease. Mov Disord Clin Pract 9(7):869\u2013878. https:\/\/doi.org\/10.1002\/mdc3.13523","journal-title":"Mov Disord Clin Pract"},{"issue":"19","key":"13639_CR30","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1212\/WNL.0b013e3181fc29c9","volume":"75","author":"JC Dalrymple-Alford","year":"2010","unstructured":"Dalrymple-Alford JC, MacAskill MR, Nakas CT et al (2010) The MoCA: well-suited screen for cognitive impairment in Parkinson disease. Neurology 75(19):1717\u20131725. https:\/\/doi.org\/10.1212\/WNL.0b013e3181fc29c9","journal-title":"Neurology"},{"issue":"2","key":"13639_CR31","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/s40520-021-01943-7","volume":"34","author":"EN Aiello","year":"2022","unstructured":"Aiello EN, Gramegna C, Esposito A et al (2022) The Montreal Cognitive Assessment (MoCA): updated norms and psychometric insights into adaptive testing from healthy individuals in Northern Italy. Aging Clin Exp Res 34(2):375\u2013382. https:\/\/doi.org\/10.1007\/s40520-021-01943-7","journal-title":"Aging Clin Exp Res"},{"key":"13639_CR32","unstructured":"Data used in the preparation of this article were obtained [on 12\/20\/2024] from the Parkinson\u2019s Progression Markers Initiative (PPMI) database (www.ppmi-info.org\/access-data-specimens\/download-data), RRID:SCR_006431. For up-to-date information on the study, visit\u00a0www.ppmi-info.org"},{"issue":"1","key":"13639_CR33","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/s007020050005","volume":"107","author":"N Giladi","year":"2000","unstructured":"Giladi N, Treves TA, Paleacu D et al (2000) Risk factors for dementia, depression and psychosis in long-standing Parkinson\u2019s disease. J Neural Transm 107(1):59\u201371. https:\/\/doi.org\/10.1007\/s007020050005","journal-title":"J Neural Transm"},{"issue":"6","key":"13639_CR34","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1002\/mds.870130605","volume":"13","author":"A Schrag","year":"1998","unstructured":"Schrag A, Ben-Shlomo Y, Brown R, Marsden CD, Quinn N (1998) Young-onset Parkinson\u2019s disease revisited--clinical features, natural history, and mortality. Mov Disord 13(6):885\u2013894. https:\/\/doi.org\/10.1002\/mds.870130605","journal-title":"Mov Disord"},{"issue":"18","key":"13639_CR35","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1212\/WNL.0b013e318253d54b","volume":"78","author":"RN Alcalay","year":"2012","unstructured":"Alcalay RN, Caccappolo E, Mejia-Santana H et al (2012) Cognitive performance of GBA mutation carriers with early-onset PD: the CORE-PD study. Neurology 78(18):1434\u20131440. https:\/\/doi.org\/10.1212\/WNL.0b013e318253d54b","journal-title":"Neurology"},{"issue":"5","key":"13639_CR36","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209699","volume":"103","author":"J Gallagher","year":"2024","unstructured":"Gallagher J, Gochanour C, Caspell-Garcia C, Parkinson\u2019s Progression Markers Initiative et al (2024) Long-term dementia risk in Parkinson disease. Neurology 103(5):e209699. https:\/\/doi.org\/10.1212\/WNL.0000000000209699","journal-title":"Neurology"},{"issue":"9","key":"13639_CR37","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000214036","volume":"105","author":"M Avenali","year":"2025","unstructured":"Avenali M, Artusi CA, Cilia R et al (2025) Long-term motor and cognitive outcome of deep brain stimulation in patients with Parkinson disease with a GBA1 pathogenic variant. Neurology 105(9):e214036. https:\/\/doi.org\/10.1212\/WNL.0000000000214036","journal-title":"Neurology"},{"issue":"11","key":"13639_CR38","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1002\/mdc3.13892","volume":"10","author":"G Devigili","year":"2023","unstructured":"Devigili G, Straccia G, Cereda E et al (2023) Unraveling autonomic dysfunction in GBA-related Parkinson\u2019s disease. Mov Disord Clin Pract 10(11):1620\u20131638. https:\/\/doi.org\/10.1002\/mdc3.13892","journal-title":"Mov Disord Clin Pract"},{"issue":"2","key":"13639_CR39","doi-asserted-by":"publisher","first-page":"335","DOI":"10.3233\/JPD-230334","volume":"14","author":"G Giannini","year":"2024","unstructured":"Giannini G, Minardi R, Barletta G et al (2024) The degree of cardiovascular autonomic dysfunction is not different in GBA-related and idiopathic Parkinson\u2019s disease patients: a case-control instrumental evaluation. J Parkinsons Dis 14(2):335\u2013346. https:\/\/doi.org\/10.3233\/JPD-230334","journal-title":"J Parkinsons Dis"},{"issue":"5","key":"13639_CR40","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-025-13086-0","volume":"272","author":"W Liu","year":"2025","unstructured":"Liu W, Han Y, Liu Y et al (2025) Impact of LRRK2 and GBA variants on orthostatic hypotension in patients with Parkinson\u2019s disease. J Neurol 272(5):369. https:\/\/doi.org\/10.1007\/s00415-025-13086-0","journal-title":"J Neurol"},{"issue":"2 ( Pt 1)","key":"13639_CR41","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1212\/wnl.41.2_part_1.202","volume":"41","author":"V Kostic","year":"1991","unstructured":"Kostic V, Przedborski S, Flaster E, Sternic N (1991) Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson\u2019s disease. Neurology 41(2 ( Pt 1)):202\u2013205. https:\/\/doi.org\/10.1212\/wnl.41.2_part_1.202","journal-title":"Neurology"},{"issue":"9","key":"13639_CR42","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1002\/mds.23068","volume":"25","author":"S Ku","year":"2010","unstructured":"Ku S, Glass GA (2010) Age of Parkinson\u2019s disease onset as a predictor for the development of dyskinesia. Mov Disord 25(9):1177\u20131182. https:\/\/doi.org\/10.1002\/mds.23068","journal-title":"Mov Disord"},{"issue":"1","key":"13639_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-04356-8","volume":"12","author":"LL Raket","year":"2022","unstructured":"Raket LL, Oudin \u00c5str\u00f6m D, Norlin JM, Kellerborg K, Martinez-Martin P, Odin P (2022) Impact of age at onset on symptom profiles, treatment characteristics and health-related quality of life in Parkinson\u2019s disease. Sci Rep 12(1):526. https:\/\/doi.org\/10.1038\/s41598-021-04356-8","journal-title":"Sci Rep"},{"issue":"12","key":"13639_CR44","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1001\/archneur.63.12.1756","volume":"63","author":"RA Hauser","year":"2006","unstructured":"Hauser RA, McDermott MP, Messing S (2006) Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease. Arch Neurol 63(12):1756\u20131760. https:\/\/doi.org\/10.1001\/archneur.63.12.1756","journal-title":"Arch Neurol"},{"issue":"3","key":"13639_CR45","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1002\/mds.23469","volume":"26","author":"MM Wickremaratchi","year":"2011","unstructured":"Wickremaratchi MM, Knipe MD, Sastry BS et al (2011) The motor phenotype of Parkinson\u2019s disease in relation to age at onset. Mov Disord 26(3):457\u2013463. https:\/\/doi.org\/10.1002\/mds.23469","journal-title":"Mov Disord"},{"issue":"11","key":"13639_CR46","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1002\/mds.10527","volume":"18","author":"A Schrag","year":"2003","unstructured":"Schrag A, Hovris A, Morley D, Quinn N, Jahanshahi M (2003) Young- versus older-onset Parkinson\u2019s disease: impact of disease and psychosocial consequences. Mov Disord 18(11):1250\u20131256. https:\/\/doi.org\/10.1002\/mds.10527","journal-title":"Mov Disord"},{"issue":"4","key":"13639_CR47","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1136\/jnnp.2005.074070","volume":"77","author":"DR Williams","year":"2006","unstructured":"Williams DR, Watt HC, Lees AJ (2006) Predictors of falls and fractures in bradykinetic rigid syndromes: a retrospective study. J Neurol Neurosurg Psychiatry 77(4):468\u2013473. https:\/\/doi.org\/10.1136\/jnnp.2005.074070","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"11","key":"13639_CR48","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1002\/mdc3.13879","volume":"10","author":"CA Artusi","year":"2023","unstructured":"Artusi CA, Geroin C, Nonnekes J et al (2023) Predictors and pathophysiology of axial postural abnormalities in Parkinsonism: a scoping review. Mov Disord Clin Pract 10(11):1585\u20131596. https:\/\/doi.org\/10.1002\/mdc3.13879","journal-title":"Mov Disord Clin Pract"},{"issue":"4","key":"13639_CR49","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1001\/archneur.60.4.529","volume":"60","author":"NJ Diederich","year":"2003","unstructured":"Diederich NJ, Moore CG, Leurgans SE, Chmura TA, Goetz CG (2003) Parkinson disease with old-age onset: a comparative study with subjects with middle-age onset. Arch Neurol 60(4):529\u2013533. https:\/\/doi.org\/10.1001\/archneur.60.4.529","journal-title":"Arch Neurol"},{"issue":"6","key":"13639_CR50","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1093\/brain\/awq059","volume":"133","author":"PA Kempster","year":"2010","unstructured":"Kempster PA, O\u2019Sullivan SS, Holton JL, Revesz T, Lees AJ (2010) Relationships between age and late progression of Parkinson\u2019s disease: a clinico-pathological study. Brain 133(6):1755\u20131762. https:\/\/doi.org\/10.1093\/brain\/awq059","journal-title":"Brain"},{"issue":"9","key":"13639_CR51","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1136\/jnnp.54.9.780","volume":"54","author":"J Blin","year":"1991","unstructured":"Blin J, Dubois B, Bonnet AM, Vidailhet M, Brandabur M, Agid Y (1991) Does ageing aggravate parkinsonian disability? J Neurol Neurosurg Psychiatry 54(9):780\u2013782. https:\/\/doi.org\/10.1136\/jnnp.54.9.780","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"6","key":"13639_CR52","doi-asserted-by":"publisher","first-page":"463","DOI":"10.3727\/000000006783981792","volume":"15","author":"G Linazasoro","year":"2006","unstructured":"Linazasoro G (2006) Cell therapy for Parkinson\u2019s disease: only young onset patients allowed? Reflections about the results of recent clinical trials with cell therapy and the progression of Parkinson\u2019s disease. Cell Transplant 15(6):463\u2013473. https:\/\/doi.org\/10.3727\/000000006783981792","journal-title":"Cell Transplant"},{"key":"13639_CR53","doi-asserted-by":"publisher","first-page":"53","DOI":"10.2147\/DNND.S34251","volume":"2","author":"N Klepac","year":"2013","unstructured":"Klepac N, Habek M, Adamec I, Baru\u0161i\u0107 AK, Bach I, Margeti\u0107 E, Lu\u0161i\u0107 I (2013) An update on the management of young-onset Parkinson\u2019s disease. Degener Neurol Neuromuscul Dis 2:53\u201362. https:\/\/doi.org\/10.2147\/DNND.S34251","journal-title":"Degener Neurol Neuromuscul Dis"},{"issue":"1","key":"13639_CR54","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/mds.28818","volume":"37","author":"SP Caminiti","year":"2022","unstructured":"Caminiti SP, Carli G, Avenali M, Blandini F, Perani D (2022) Clinical and dopamine transporter imaging trajectories in a cohort of Parkinson\u2019s disease patients with GBA mutations. Mov Disord 37(1):106\u2013118. https:\/\/doi.org\/10.1002\/mds.28818","journal-title":"Mov Disord"},{"issue":"7","key":"13639_CR55","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1093\/brain\/awy146","volume":"141","author":"JL Robinson","year":"2018","unstructured":"Robinson JL, Lee EB, Xie SX et al (2018) Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated. Brain 141(7):2181\u20132193. https:\/\/doi.org\/10.1093\/brain\/awy146","journal-title":"Brain"},{"issue":"2","key":"13639_CR56","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.parkreldis.2007.07.012","volume":"14","author":"SM Calne","year":"2008","unstructured":"Calne SM, Lidstone SC, Kumar A (2008) Psychosocial issues in young-onset Parkinson\u2019s disease: current research and challenges. Parkinsonism Relat Disord 14(2):143\u2013150. https:\/\/doi.org\/10.1016\/j.parkreldis.2007.07.012","journal-title":"Parkinsonism Relat Disord"},{"key":"13639_CR57","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jns.2016.08.059","volume":"370","author":"M Swan","year":"2016","unstructured":"Swan M, Doan N, Ortega RA et al (2016) Neuropsychiatric characteristics of GBA-associated Parkinson disease. J Neurol Sci 370:63\u201369. https:\/\/doi.org\/10.1016\/j.jns.2016.08.059","journal-title":"J Neurol Sci"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13639-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-026-13639-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13639-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:04:52Z","timestamp":1773785092000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-026-13639-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["13639"],"URL":"https:\/\/doi.org\/10.1007\/s00415-026-13639-x","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"6 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the authors declare that they have no conflicts of interest relevant to this manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interests"}},{"value":"The Local Ethics Committee approved the study in each center (protocol number 0044208), and all participants provided written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standard statement"}}],"article-number":"111"}}