{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T18:30:24Z","timestamp":1793817024536,"version":"4.6.1"},"reference-count":27,"publisher":"BMJ","issue":"12","funder":[{"DOI":"10.13039\/501100000304","name":"Parkinson's UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To use a data-driven approach to determine the existence and natural history of subtypes of Parkinson\u2019s disease (PD)\u00a0using two large independent cohorts of patients newly diagnosed with this condition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>1601 and 944 patients with\u00a0idiopathic PD,\u00a0from Tracking Parkinson\u2019s and Discovery cohorts, respectively, were evaluated in motor, cognitive and non-motor domains at the baseline assessment. Patients were recently diagnosed at entry (within 3.5 years of diagnosis) and were followed\u00a0up every 18 months. We used a factor analysis followed by a k-means cluster analysis, while prognosis was measured using random slope and intercept models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified four clusters: (1)\n                      <jats:italic>\ufeff<\/jats:italic>\n                      <jats:italic>fast motor progression<\/jats:italic>\n                      with symmetrical motor disease, poor olfaction, cognition and postural hypotension; (2)\n                      <jats:italic>mild motor and non-motor disease<\/jats:italic>\n                      with intermediate motor progression; (3)\n                      <jats:italic>severe motor disease<\/jats:italic>\n                      ,\n                      <jats:italic>poor psychological well-being<\/jats:italic>\n                      and\n                      <jats:italic>\ufeff<\/jats:italic>\n                      <jats:italic>poor sleep<\/jats:italic>\n                      with an intermediate motor progression; (4)\n                      <jats:italic>slow motor progression<\/jats:italic>\n                      with tremor-dominant, unilateral disease. Clusters were moderately to substantially stable across the two cohorts (kappa 0.58). Cluster 1 had the fastest motor progression in Tracking Parkinson\u2019s at 3.2 (95% CI 2.8 to 3.6) UPDRS III points per year while cluster 4 had the slowest at 0.6 (0.1\u20131.1). In Tracking Parkinson\u2019s, cluster 2 had the largest response to levodopa 36.3% and cluster 4 the lowest 28.8%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We have found four novel clusters that replicated well across two independent early PD cohorts and were associated with levodopa response and motor progression rates. This has potential implications for better understanding disease pathophysiology and the relevance of patient stratification in future clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2018-318337","type":"journal-article","created":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T12:15:19Z","timestamp":1532520919000},"page":"1279-1287","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":177,"title":["Developing and validating Parkinson\u2019s disease subtypes and their motor and cognitive progression"],"prefix":"10.1136","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3419-0354","authenticated-orcid":false,"given":"Michael","family":"Lawton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoav","family":"Ben-Shlomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret 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