{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T22:40:59Z","timestamp":1778712059637,"version":"3.51.4"},"reference-count":57,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We used data from a multi\u2010site, international, prospective cohort study to explore the impact of dopamine system\u2010related biomarkers on CI in PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PD participants were assessed annually from disease onset out to 7\u2009years, and CI determined by applying cut\u2010offs to four measures: (1) Montreal Cognitive Assessment; (2) detailed neuropsychological test battery; (3) Movement Disorder Society\u2010Unified Parkinson's Disease Rating Scale (MDS\u2010UPDRS) cognition score; and (4) site investigator diagnosis of CI (mild cognitive impairment or dementia). The dopamine system was assessed by serial Iodine\u2010123 Ioflupane dopamine transporter (DAT) imaging, genotyping, and levodopa equivalent daily dose (LEDD) recorded at each assessment. Multivariate longitudinal analyses, with adjustment for multiple comparisons, determined the association between dopamine system\u2010related biomarkers and CI, including persistent impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Demographic and clinical variables associated with CI were higher age, male sex, lower education, non\u2010White race, higher depression and anxiety scores and higher MDS\u2010UPDRS motor score. For the dopamine system, lower baseline mean striatum dopamine transporter values (<jats:italic>P<\/jats:italic> range 0.003\u20130.005) and higher LEDD over time (<jats:italic>P<\/jats:italic> range\u2009&lt;0.001\u20130.01) were significantly associated with increased risk for CI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results provide preliminary evidence that alterations in the dopamine system predict development of clinically\u2010relevant, cognitive impairment in Parkinson's disease. If replicated and determined to be causative, they demonstrate that the dopamine system is instrumental to cognitive health status throughout the disease course.<\/jats:p><\/jats:sec><jats:sec><jats:title>TRIAL REGISTRATION<\/jats:title><jats:p>Parkinson's Progression Markers Initiative is registered with <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> (NCT01141023).<\/jats:p><\/jats:sec>","DOI":"10.1002\/mdc3.13751","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T01:11:21Z","timestamp":1681175481000},"page":"943-955","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impact of the Dopamine System on Long\u2010Term Cognitive Impairment in Parkinson Disease: An Exploratory Study"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0633-7168","authenticated-orcid":false,"given":"Daniel","family":"Weintraub","sequence":"first","affiliation":[{"name":"Department of Psychiatry Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9025-137X","authenticated-orcid":false,"given":"Marina","family":"Picillo","sequence":"additional","affiliation":[{"name":"Assistant Professor in Neurology at the Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d University of Salerno  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunkeun Ryan","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health University of Iowa  Iowa City Iowa 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