{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T02:17:43Z","timestamp":1793758663819,"version":"4.6.1"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson's disease (PD) varies widely across individuals in clinical manifestations and course of progression. Identification of distinct biological subtypes could explain this heterogeneity, identify its pathophysiology, and predict disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Our aim was to compare longitudinal clinical trajectories and brain atrophy patterns between clinical subtypes defined at the baseline de novo PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed data from 421 PD patients (mean follow\u2010up: 8.2\u2009years) in the Parkinson's Progression Markers Initiative (PPMI). Using multi\u2010domain motor and non\u2010motor criteria, de novo patients were classified into \u201cmild motor\u2010predominant\u201d (n\u2009=\u2009223), \u201cintermediate\u201d (n\u2009=\u2009146), and \u201cdiffuse\u2010malignant\u201d (n\u2009=\u200952) subtypes. Deformation\u2010based morphometry was performed on T1\u2010weighted magnetic resonance imaging (MRIs) from 128 PD patients with at least two MRIs (71 mild motor\u2010predominant, 42 intermediate, and 15 diffuse\u2010malignant) and 60 controls, with an average MRI follow\u2010up duration of 3.4\u2009\u00b1\u20091.1 in the PD cohort. Mixed\u2010effects models compared clinical progression and longitudinal pattern of regional atrophy across subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The diffuse\u2010malignant subtype exhibited faster worsening of motor severity (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.007), cognition (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001), and activities of daily living (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001) compared to mild motor\u2010predominant subtype over 8\u2009years. These findings remained statistically significant after an age\u2010matched subgroup analysis and adjustment for the levodopa treatment. Accelerated atrophy was observed in the precuneus, temporal and fusiform gyri, cerebellum, and other regions (corrected\u2010\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Longitudinal analysis revealed distinct patterns of clinical progression and regional atrophy in PD subtypes, with the diffuse\u2010malignant subtype showing more severe neurodegeneration and clinical deterioration suggesting existence of diverse pathophysiological mechanisms in PD. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.30229","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T04:29:13Z","timestamp":1748233753000},"page":"1572-1583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Distinct Longitudinal Clinical\u2010Neuroanatomical Trajectories in Parkinson's Disease Clinical Subtypes: Insight toward Precision Medicine"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9255-9351","authenticated-orcid":false,"given":"Seyed\u2010Mohammad","family":"Fereshtehnejad","sequence":"first","affiliation":[{"name":"Division of Neurology, Toronto Western Hospital University of Toronto  Toronto Ontario Canada"},{"name":"The Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic Toronto Western Hospital, UHN  Toronto Ontario Canada"},{"name":"Department of Neurobiology, Care Sciences and Society (NVS) Karolinska Institute  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roqaie","family":"Moqadam","sequence":"additional","affiliation":[{"name":"Douglas Mental Health University Institute, Department of Psychiatry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houman","family":"Azizi","sequence":"additional","affiliation":[{"name":"Douglas Mental Health University Institute, Department of Psychiatry McGill University  Montreal Quebec Canada"},{"name":"Integrated Program in Neuroscience McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6468-4734","authenticated-orcid":false,"given":"Ronald B.","family":"Postuma","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Dadar","sequence":"additional","affiliation":[{"name":"Douglas Mental Health University Institute, Department of Psychiatry McGill University  Montreal Quebec Canada"},{"name":"Integrated Program in Neuroscience McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony E.","family":"Lang","sequence":"additional","affiliation":[{"name":"Division of Neurology, Toronto Western Hospital University of Toronto  Toronto Ontario Canada"},{"name":"The Edmond J. 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