{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:16:23Z","timestamp":1789398983770,"version":"build-2803163510"},"reference-count":58,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2023,7,26]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Identifying a meaningful progression metric for Parkinson\u2019s disease (PD) that reflects heterogeneity remains a challenge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Using data from the Parkinson\u2019s Progression Markers Initiative (PPMI) de novo PD cohort, we monitored 25 milestones across six domains (\u201cwalking and balance\u201d; \u201cmotor complications\u201d; \u201ccognition\u201d; \u201cautonomic dysfunction\u201d; \u201cfunctional dependence\u201d; \u201cactivities of daily living\u201d). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Half of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at the next annual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age ( p\u200a&lt;\u200a0.0001), greater MDS-UPDRS total scores ( p\u200a&lt;\u200a0.0001), higher GDS-15 depression scores ( p\u200a=\u200a0.0341), lower dopamine transporter binding ( p\u200a=\u200a0.0043), and lower CSF total \u03b1-synuclein levels ( p\u200a=\u200a0.0030). Symptomatic treatment was not significantly associated with reaching a milestone ( p\u200a=\u200a0.1639).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Clinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jpd-223433","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T11:43:14Z","timestamp":1689334994000},"page":"899-916","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":66,"title":["Parkinson\u2019s Progression Markers Initiative: A Milestone-Based Strategy to Monitor Parkinson\u2019s Disease Progression"],"prefix":"10.1177","volume":"13","author":[{"given":"Michael C.","family":"Brumm","sequence":"first","affiliation":[{"name":"Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Siderowf","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Simuni","sequence":"additional","affiliation":[{"name":"Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Burghardt","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Caspell-Garcia","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana M.","family":"Chahine","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brit","family":"Mollenhauer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Goettingen, Goettingen, Germany"},{"name":"Paracelsus-Elena Klinik, Kassel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Foroud","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Galasko","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana","family":"Merchant","sequence":"additional","affiliation":[{"name":"Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Arnedo","sequence":"additional","affiliation":[{"name":"The Michael J. Fox Foundation for Parkinson\u2019s Research, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J.","family":"Hutten","sequence":"additional","affiliation":[{"name":"The Michael J. Fox Foundation for Parkinson\u2019s Research, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa N.","family":"O\u2019Grady","sequence":"additional","affiliation":[{"name":"The Michael J. Fox Foundation for Parkinson\u2019s Research, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen L.","family":"Poston","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Tanner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, SanFrancisco, CA, USA"},{"name":"Parkinson\u2019s Disease Research, Education and Clinical Center, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Weintraub","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Departmentof 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