{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:40:45Z","timestamp":1792456845335,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Peripheral immune dysregulation has been implicated in Parkinson's disease (PD) progression, but whether motor deterioration reflects accelerated nigrostriatal degeneration or residual dopaminergic reserve remains unclear.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To examine whether baseline and time\u2010varying neutrophil\u2010to\u2010lymphocyte ratio (NLR) relate to motor progression and striatal dopamine transporter (DAT) decline, and whether baseline DAT modifies the NLR\u2013motor relationship.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We analyzed 7\u2009years of Parkinson's Progression Markers Initiative (PPMI) data from 335 drug\u2010naive patients with PD and 305 healthy controls. Linear mixed\u2010effects models assessed NLR trajectories, longitudinal Unified Parkinson's Disease Rating Scale\u2010Part III (UPDRS\u2010III) and DAT associations, and moderation by baseline DAT; follow\u2010up motor assessments were ON\u2010medication.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n NLR<\/jats:styled-content>\n remained higher in\n PD<\/jats:styled-content>\n than controls (\n P<\/jats:italic>\n \u2009<\u20090.001). A 1\n SD<\/jats:styled-content>\n higher baseline\n NLR<\/jats:styled-content>\n was associated with an additional 0.350\n UPDRS<\/jats:styled-content>\n \u2010\n III<\/jats:styled-content>\n points\/year (\n P<\/jats:italic>\n \u2009<\u20090.001), while higher\u2010than\u2010usual visit\u2010wise\n NLR<\/jats:styled-content>\n was associated with higher concurrent motor severity (\n \u03b2<\/jats:italic>\n \u2009=\u20090.352,\n P<\/jats:italic>\n \u2009=\u20090.041). Neither baseline nor time\u2010varying\n NLR<\/jats:styled-content>\n was consistently associated with\n DAT<\/jats:styled-content>\n decline. Higher baseline\n DAT<\/jats:styled-content>\n binding moderated\n NLR<\/jats:styled-content>\n \u2010related motor progression in the left caudate (\n \u03b2<\/jats:italic>\n \u2009=\u20090.326,\n P<\/jats:italic>\n \u2009<\u20090.001), right caudate (\n \u03b2<\/jats:italic>\n \u2009=\u20090.183,\n P<\/jats:italic>\n \u2009=\u20090.036), and left putamen (\n \u03b2<\/jats:italic>\n \u2009=\u20090.168,\n P<\/jats:italic>\n \u2009=\u20090.023); within the\n DAT<\/jats:styled-content>\n \u2010imaging interval, moderation persisted in the left caudate (\n \u03b2<\/jats:italic>\n \u2009=\u20090.314,\n P<\/jats:italic>\n \u2009=\u20090.044) and left putamen (\n \u03b2<\/jats:italic>\n \u2009=\u20090.223,\n P<\/jats:italic>\n \u2009=\u20090.047).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Higher baseline NLR predicted faster treated\u2010state motor worsening, while visit\u2010wise NLR tracked concurrent severity. These associations were not accompanied by clear evidence of accelerated DAT decline, supporting a reserve\u2010dependent relationship between peripheral inflammation and motor progression. \u00a9 2026 The Author(s).\n 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.70549","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:26:45Z","timestamp":1790054805000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Striatal Dopaminergic Reserve Shapes the Longitudinal Impact of Peripheral Immune Activation on Motor Progression in Parkinson's Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9003-5781","authenticated-orcid":false,"given":"Osman","family":"Kahveci","sequence":"first","affiliation":[{"name":"Graduate School of Health Sciences Istanbul University Istanbul T\u00fcrkiye"},{"name":"Department of Physiology, Faculty of Medicine Bezmialem Vak\u0131f University Istanbul T\u00fcrkiye"},{"name":"Department of Physiology, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7896-3681","authenticated-orcid":false,"given":"Ula\u015f","family":"Ay","sequence":"additional","affiliation":[{"name":"Department of Physiology, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"},{"name":"Neuroimaging Unit, Hulusi Beh\u00e7et Life Sciences Research Laboratory Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6803-734X","authenticated-orcid":false,"given":"Tamer","family":"Demiralp","sequence":"additional","affiliation":[{"name":"Department of Physiology, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"},{"name":"Neuroimaging Unit, Hulusi Beh\u00e7et Life Sciences Research Laboratory Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson disease","volume":"3","author":"Poewe W","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.bbi.2025.04.028","article-title":"Peripheral\u2010central immune crosstalk in Parkinson's disease and its association with clinical severity","volume":"128","author":"Greenland JC","year":"2025","journal-title":"Brain Behav Immun"},{"issue":"1","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13024-025-00827-y","article-title":"Immune cell metabolic dysfunction in Parkinson's disease","volume":"20","author":"Mark JR","year":"2025","journal-title":"Mol Neurodegener"},{"issue":"10","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1093\/brain\/awae177","article-title":"The immune system in Parkinson's disease: what we know so far","volume":"147","author":"Roodveldt C","year":"2024","journal-title":"Brain"},{"issue":"11","key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41577-022-00684-6","article-title":"Inflammation and immune dysfunction in Parkinson disease","volume":"22","author":"Tansey MG","year":"2022","journal-title":"Nat Rev Immunol"},{"issue":"2","key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s13311-020-00994-4","article-title":"Imaging familial and sporadic neurodegenerative disorders associated with parkinsonism","volume":"18","author":"Brooks DJ","year":"2021","journal-title":"Neurotherapeutics"},{"issue":"12","key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.2169\/internalmedicine.2489-18","article-title":"Dopamine transporter imaging in Parkinson disease: progressive changes and therapeutic modification after anti\u2010parkinsonian medications","volume":"58","author":"Ikeda K","year":"2019","journal-title":"Intern Med"},{"issue":"1","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1212\/WNL.46.1.231","article-title":"[123I] beta\u2010CIT\/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi\u2010Parkinson's disease","volume":"46","author":"Marek KL","year":"1996","journal-title":"Neurology"},{"issue":"5","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1002\/mds.29369","article-title":"Peripheral inflammation is associated with dopaminergic degeneration in Parkinson's disease","volume":"38","author":"Mu\u00f1oz\u2010Delgado L","year":"2023","journal-title":"Mov Disord"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2025.1682006","article-title":"Peripheral\u2010central immune interactions in Parkinson's disease: insights into innate and adaptive immunity","volume":"18","author":"Tumpa JJ","year":"2025","journal-title":"Front Mol Neurosci"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2024.1377994","article-title":"Association analysis of dopaminergic degeneration and the neutrophil\u2010to\u2010lymphocyte ratio in Parkinson's disease","volume":"16","author":"Zhang F","year":"2024","journal-title":"Front Aging Neurosci"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.64898\/2026.02.17.706426"},{"issue":"4","key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.pneurobio.2011.09.005","article-title":"The Parkinson Progression Marker Initiative (PPMI)","volume":"95","author":"Marek K","year":"2011","journal-title":"Prog Neurobiol"},{"issue":"12","key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1002\/acn3.644","article-title":"The Parkinson's Progression Markers Initiative (PPMI): establishing a PD biomarker cohort","volume":"5","author":"Marek K","year":"2018","journal-title":"Ann Clin Transl Neurol"},{"issue":"7","key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/mds.26563","article-title":"Serum immune markers and disease progression in an incident Parkinson's disease cohort (ICICLE\u2010PD)","volume":"31","author":"Williams\u2010Gray CH","year":"2016","journal-title":"Mov Disord"},{"issue":"1","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","DOI":"10.1007\/s10571-026-01708-8","article-title":"Peripheral inflammatory biomarkers in Parkinson's disease: clinical correlations and stratification","volume":"46","author":"Jiang GY","year":"2026","journal-title":"Cell Mol Neurobiol"},{"issue":"1","key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41531-023-00449-5","article-title":"A systematic review and meta\u2010analysis of inflammatory biomarkers in Parkinson's disease","volume":"9","author":"Qu Y","year":"2023","journal-title":"NPJ Parkinsons Dis"},{"issue":"1","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/ana.27223","article-title":"Dopamine transporter imaging as objective monitoring biomarker in Parkinson's disease","volume":"98","author":"Dzialas V","year":"2025","journal-title":"Ann Neurol"},{"issue":"1","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"10566","DOI":"10.1038\/s41598-018-28646-w","article-title":"Reference values for white blood\u2010cell\u2010based inflammatory markers in the Rotterdam Study: a population\u2010based prospective cohort study","volume":"8","author":"Fest 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neutrophil\u2010to\u2010lymphocyte ratio is associated with multiple sclerosis","volume":"4","author":"Hasselbalch IC","year":"2018","journal-title":"Mult Scler J Exp Transl Clin"},{"issue":"8","key":"e_1_2_9_25_1","article-title":"The relationship between systemic inflammatory index and other inflammatory markers with clinical severity of the disease in patients with Parkinson's disease","volume":"13","author":"Alagoz AN","year":"2025","journal-title":"Biomedicine"},{"issue":"4","key":"e_1_2_9_26_1","doi-asserted-by":"crossref","DOI":"10.1007\/s10072-026-09002-7","article-title":"Peripheral inflammation predicts motor, cognitive, and disease progression in Parkinson's disease: a 4\u2010year longitudinal study from the PPMI cohorts","volume":"47","author":"Chen Z","year":"2026","journal-title":"Neurol Sci"},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbi.2025.106155","article-title":"Peripheral inflammation drives cognitive and motor decline in Parkinson's disease through glymphatic dysfunction and white matter free water accumulation","volume":"131","author":"Ruan X","year":"2026","journal-title":"Brain Behav Immun"},{"issue":"1","key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41531-025-01019-7","article-title":"Peripheral inflammation's variable impact on cognitive and symptomatic outcomes in Parkinson's disease: a longitudinal and cross\u2010sectional analysis","volume":"11","author":"He P","year":"2025","journal-title":"NPJ Parkinsons Dis"},{"issue":"2","key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1159\/000545314","article-title":"Association of neutrophil\u2010to\u2010lymphocyte ratio with incidence and disease progression in Parkinson's disease","volume":"60","author":"Xiao Y","year":"2026","journal-title":"Neuroepidemiology"},{"issue":"9","key":"e_1_2_9_30_1","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1002\/acn3.52144","article-title":"Neutrophil\u2010to\u2010lymphocyte ratio and longitudinal cognitive performance in Parkinson's disease","volume":"11","author":"Lucero J","year":"2024","journal-title":"Ann Clin Transl Neurol"},{"issue":"9","key":"e_1_2_9_31_1","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.1007\/s00415-023-11790-3","article-title":"Association between peripheral adaptive immune markers and disease progression in Parkinson's disease","volume":"270","author":"Xiao Y","year":"2023","journal-title":"J Neurol"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70549","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70549","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70549","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:26:49Z","timestamp":1790054809000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":30,"alternative-id":["10.1002\/mds.70549"],"URL":"https:\/\/doi.org\/10.1002\/mds.70549","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]},"assertion":[{"value":"2026-06-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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