{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:09:23Z","timestamp":1790838563951,"version":"4.1.0"},"reference-count":87,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"James & Diana Ramsay Foundation"},{"DOI":"10.13039\/501100001039","name":"Neurosurgical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001039","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Oxford University Innovations"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Geriatr Psychiatry Neurol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Currently, prognosis of Parkinson\u2019s Disease (PD) is limited. Emerging literature highlights potential of multi-modal biomarkers and neuroimaging to provide critical insight into clinical progression, potentially improving prediction of long-term outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data were extracted from the Parkinson\u2019s Progression Markers Initiative (PPMI). Hierarchical clustering was applied to Movement Disorder Society Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) scores at year-five follow-up, identifying two clusters. Differences in progression, as well as retrospective assessment of baseline differences, between clusters were explored for pathological biomarkers, neuroimaging, and prodromal measures. Additionally, logistic regression, receiver operating characteristic curve analyses and machine learning were employed to determine utility of variables at baseline as predictors of cluster membership.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The more impaired cluster demonstrated worse motor and non-motor outcomes, including higher rates of dementia and cognitive complaints at year-five, as well as more profound rigidity than cluster one. Further, retrospective comparisons showed cluster two performing worse in all prodromal measures and demonstrated lower striatal dopamine transporter and cognitive ability. Logistic regression determined that membership in this cluster was predicted by higher autonomic dysfunction and p-tau, along with reduced smell and alpha-syn, predicting 49.1% of variance (AUC = 0.92). This was significantly higher (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.001) than the model including MDS-UPDRS scores alone, only accounting for 27.4% of variance (AUC = 0.74). Findings were corroborated by machine learning, whereby multi-modal assessment corresponded to 74% classification accuracy, compared to 60% with MDS-UPDRS alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Prediction of more marked impairment at year-five was substantially improved via multi-modal assessment, specifically, pathological biomarkers, suggesting that incorporating biomarkers into clinical criteria could enhance long-term prognosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/08919887251397641","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T17:11:07Z","timestamp":1763053867000},"page":"471-487","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Utility of Baseline Pathological, Neuroimaging and Clinical Markers for Prognosis in Early Parkinson\u2019s Disease"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5160-5435","authenticated-orcid":false,"given":"Angus","family":"McNamara","sequence":"first","affiliation":[{"name":"University of Adelaide"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0587-5493","authenticated-orcid":false,"given":"Benjamin Paul","family":"Ellul","sequence":"additional","affiliation":[{"name":"University of Adelaide"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Baetu","sequence":"additional","affiliation":[{"name":"University of Adelaide"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6043-0166","authenticated-orcid":false,"given":"Mark","family":"Jenkinson","sequence":"additional","affiliation":[{"name":"University of Adelaide"},{"name":"South Australian Health and Medical Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Laurenz","sequence":"additional","affiliation":[{"name":"University of Adelaide"},{"name":"South Australian Health and Medical Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsey","family":"Collins-Praino","sequence":"additional","affiliation":[{"name":"University of Adelaide"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26424"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27362"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870090112"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-017-0738-x"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.704906"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1590\/s1980-57642011dn05030003"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-017847"},{"key":"e_1_3_7_10_2","volume-title":"Alzheimer Disease","author":"Kumar A","year":"2023","unstructured":"Kumar A, Sidhu J, Goyal A, Tsao JW. Alzheimer Disease. Tampa, FL: StatPearls Publishing LLC; 2023."},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.004"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12390"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14357"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000200878"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(23)00109-6"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.4398"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00405-2"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42305-3"},{"issue":"4","key":"e_1_3_7_19_2","first-page":"290","article-title":"HPLC-free and cassette-based nucleophilic production of [18F] FDOPA for clinical use","volume":"11","author":"Jiang H","year":"2021","unstructured":"Jiang H, Jain MK, Cai H. HPLC-free and cassette-based nucleophilic production of [18F] FDOPA for clinical use. Am J Nucl Med Mol Imaging. 2021;11(4):290-299.","journal-title":"Am J Nucl Med Mol Imaging"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(95)00316-T"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.45.6.1138"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(09)70818-1"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2011.09.005"},{"issue":"2","key":"e_1_3_7_24_2","first-page":"115","article-title":"Self-reported autonomic symptoms in Parkinson\u2019s disease: properties of the SCOPA-AUT scale","volume":"20","author":"Bostantjopoulou S","year":"2016","unstructured":"Bostantjopoulou S, Katsarou Z, Danglis I, Karakasis H, Milioni D, Falup-Pecurariu C. Self-reported autonomic symptoms in Parkinson\u2019s disease: properties of the SCOPA-AUT scale. Hippokratia. 2016;20(2):115-120.","journal-title":"Hippokratia"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21740"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.1288\/00005537-198402000-00004"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00156"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-023-02627-4"},{"key":"e_1_3_7_29_2","doi-asserted-by":"publisher","DOI":"10.14336\/ad.2021.0519"},{"key":"e_1_3_7_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00301"},{"key":"e_1_3_7_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26572"},{"key":"e_1_3_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prdoa.2023.100187"},{"key":"e_1_3_7_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13845"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.30133"},{"key":"e_1_3_7_35_2","doi-asserted-by":"publisher","DOI":"10.1177\/08919887251366638"},{"key":"e_1_3_7_36_2","doi-asserted-by":"crossref","unstructured":"Kassambara A. Mundt F. Factoextra: extract and visualize the results of multivariate data analyses. CRAN: Contributed Packages. 2016.","DOI":"10.32614\/CRAN.package.factoextra"},{"key":"e_1_3_7_37_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v061.i06"},{"issue":"10","key":"e_1_3_7_38_2","first-page":"1747","article-title":"The substantia nigra in Parkinson disease: proton density-weighted spin-echo and fast short inversion time inversion-recovery MR findings","volume":"23","author":"Oikawa H","year":"2002","unstructured":"Oikawa H, Sasaki M, Tamakawa Y, Ehara S, Tohyama K. The substantia nigra in Parkinson disease: proton density-weighted spin-echo and fast short inversion time inversion-recovery MR findings. AJNR Am J Neuroradiol. 2002;23(10):1747-1756.","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_3_7_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp328"},{"key":"e_1_3_7_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.09.015"},{"key":"e_1_3_7_41_2","unstructured":"Team RDCR. A language and environment for statistical computing. 2010."},{"key":"e_1_3_7_42_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v050.i12"},{"key":"e_1_3_7_43_2","volume-title":"R Package","author":"L\u00fcdecke D","year":"2021","unstructured":"L\u00fcdecke D. sjPlot: data visualization for statistics in social science. In: R Package. Vienna: R Foundation for Statistical Computing; 2021."},{"key":"e_1_3_7_44_2","volume-title":"Astrophysics Source Code Library","author":"Kuhn M","year":"2015","unstructured":"Kuhn M. Caret: Classification and Regression Training. Astrophysics Source Code Library; 2015. pp.ascl-1505."},{"key":"e_1_3_7_45_2","first-page":"2825","article-title":"Scikit-learn: machine learning in python","volume":"12","author":"Pedregosa F","year":"2011","unstructured":"Pedregosa F, Varoquaux G, Gramfort A, et al. Scikit-learn: machine learning in python. The Journal of Machine Learning Research. 2011;12:2825-2830.","journal-title":"The Journal of Machine Learning Research"},{"key":"e_1_3_7_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20513"},{"key":"e_1_3_7_47_2","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000002461"},{"key":"e_1_3_7_48_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.10.1611"},{"key":"e_1_3_7_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046813"},{"key":"e_1_3_7_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.04.002"},{"key":"e_1_3_7_51_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2005.081711"},{"key":"e_1_3_7_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.04.020"},{"key":"e_1_3_7_53_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjment-2024-301062"},{"key":"e_1_3_7_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2008.09.003"},{"key":"e_1_3_7_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-016-1650-2"},{"key":"e_1_3_7_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep44872"},{"key":"e_1_3_7_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1552-2"},{"key":"e_1_3_7_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27806"},{"key":"e_1_3_7_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134564"},{"key":"e_1_3_7_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-94345-8"},{"key":"e_1_3_7_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26754"},{"key":"e_1_3_7_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq008"},{"key":"e_1_3_7_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(11)70014-x"},{"key":"e_1_3_7_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12176"},{"key":"e_1_3_7_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.12.007"},{"key":"e_1_3_7_66_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-020-01776-5"},{"key":"e_1_3_7_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad388"},{"key":"e_1_3_7_68_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f39a78"},{"key":"e_1_3_7_69_2","doi-asserted-by":"publisher","DOI":"10.1177\/17562864221150329"},{"key":"e_1_3_7_70_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000208033"},{"key":"e_1_3_7_71_2","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12178"},{"key":"e_1_3_7_72_2","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12613"},{"key":"e_1_3_7_73_2","doi-asserted-by":"publisher","DOI":"10.3233\/jpd-181518"},{"key":"e_1_3_7_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-021-00256-w"},{"key":"e_1_3_7_75_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26883"},{"key":"e_1_3_7_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2020.106181"},{"key":"e_1_3_7_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-024-00631-3"},{"key":"e_1_3_7_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1353-8020(11)70062-1"},{"key":"e_1_3_7_79_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.569777"},{"key":"e_1_3_7_80_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.2.266"},{"key":"e_1_3_7_81_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002768"},{"key":"e_1_3_7_82_2","first-page":"429","article-title":"Autonomic symptoms in motor subtypes of Parkinson's disease","author":"Arnao V","year":"2021","unstructured":"Arnao V, Pignolo A, Dav\u00ec C, et al. Autonomic symptoms in motor subtypes of Parkinson's disease. J Neurol Sci. 2021;429.","journal-title":"J Neurol Sci"},{"key":"e_1_3_7_83_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316136"},{"key":"e_1_3_7_84_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23121"},{"key":"e_1_3_7_85_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.24996"},{"key":"e_1_3_7_86_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.644"},{"key":"e_1_3_7_87_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000148603.44618.19"},{"key":"e_1_3_7_88_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1076657"}],"container-title":["Journal of Geriatric Psychiatry and Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08919887251397641","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/08919887251397641","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08919887251397641","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:17:15Z","timestamp":1777501035000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/08919887251397641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,13]]},"references-count":87,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1177\/08919887251397641"],"URL":"https:\/\/doi.org\/10.1177\/08919887251397641","relation":{},"ISSN":["0891-9887","1552-5708"],"issn-type":[{"value":"0891-9887","type":"print"},{"value":"1552-5708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,13]]}}}