{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:24:48Z","timestamp":1787225088949,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"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":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Combined effects of multiple risk factors on incident late\u2010onset Parkinson's disease (PD; LOPD) remain poorly characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of this study was to quantify the impact of joint risk exposures and estimate the contribution of potentially modifiable factors to incident LOPD risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective cohort study, 311,261 UK Biobank participants aged \u226550\u2009years and free of PD at baseline were followed for up to 15\u2009years. During follow\u2010up, 2769 individuals developed incident LOPD. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) for 65 candidate risk factors. Combinations of two (pairs) or three (triplets) risk factors were evaluated for additive interaction. Population\u2010attributable fractions (PAFs) were estimated for potentially modifiable risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eighteen risk factors (mean HR, 1.43) were independently associated with incident LOPD and subsequently evaluated as joint exposures. Thirteen pairs (mean HR, 2.00) and 14 triplets (mean HR, 4.21) demonstrated significant positive additive interaction and larger effect sizes than individual factors alone. A limited set of modifiable factors\u2014loneliness, low handgrip strength, epilepsy, hearing loss, and diabetes\u2014within the highest\u2010risk pairs (HR range, 2.55\u20132.93) and triplets (HR range, 5.28\u201312.24) emerged as major contributors to elevated LOPD risk. Removing modifiable exposures from additive pairs and triplets was associated with reduction in mean HRs of 30% and 49%, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.001). At the population level, removal of modifiable risk factors accounted for an estimated 34.4% reduction in LOPD incidence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Integrating traditional single\u2010factor approaches with high\u2010risk additive joint exposure profiles may improve risk stratification and inform targeted prevention strategies for incident PD. \u00a9 2026 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.70462","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:07:15Z","timestamp":1786518435000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Joint Risk Factor Combinations with Additive Interaction Increase the Risk of Parkinson's Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-2083","authenticated-orcid":false,"given":"Andrea","family":"Quattrone","sequence":"first","affiliation":[{"name":"Institute of Neurology, Department of Medical and Surgical Sciences Magna Graecia University  Catanzaro Italy"},{"name":"Neuroscience Research Centre, Magna Graecia University  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7172-8520","authenticated-orcid":false,"given":"Basilio","family":"Vescio","sequence":"additional","affiliation":[{"name":"Neuroscience Research Centre, Magna Graecia University  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3723-6096","authenticated-orcid":false,"given":"Fulvia","family":"Arcuri","sequence":"additional","affiliation":[{"name":"Neuroscience Research Centre, Magna Graecia University  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Chiarella","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Audiology Unit, Phoniatrics and Vestibology, Regional Center of Cochlear Implants and ENT Diseases Magna Graecia University  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3813-283X","authenticated-orcid":false,"given":"Jolanda","family":"Buonocore","sequence":"additional","affiliation":[{"name":"Neuroscience Research Centre, Magna Graecia University  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2001-957X","authenticated-orcid":false,"given":"Aldo","family":"Quattrone","sequence":"additional","affiliation":[{"name":"Neuroscience Research Centre, Magna Graecia University  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-7568(24)00094-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30230-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-025-13498-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2024.107026"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2012.05.004"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-323646"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD013856.pub2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20682"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/11316780-000000000-00000"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d5a4a3"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv335"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200226"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13523"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23687"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12061-022-09486-8"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19970228)16:4<385::AID-SIM380>3.0.CO;2-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14269"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70287-X"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29349"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1004092"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-011-9554-9"},{"key":"e_1_2_9_24_1","first-page":"179","volume-title":"Volume 1 Machine Learning under Resource Constraints \u2010 Fundamentals","author":"Lenssen L","year":"2023"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyac217"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.02.002"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9497147"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000012884"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.709846"},{"key":"e_1_2_9_30_1","volume-title":"Integrated Outpatient Palliative Care in Oncology","author":"Fulton J","year":"2017"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3382"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-024-00810-2"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/2050312120910358"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2024.122891"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.0003"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.3568"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-212725"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-023-00970-0"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.0183"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.4699"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006919"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2022.08.008"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12378"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.3902"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-024-00700-7"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.70206"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29298"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1584"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24396"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005522"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-023-02209-x"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01296-0"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2025.1525248"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70462","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70462","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70462","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:41:47Z","timestamp":1787222507000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":52,"alternative-id":["10.1002\/mds.70462"],"URL":"https:\/\/doi.org\/10.1002\/mds.70462","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"assertion":[{"value":"2026-05-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"mds.70462"}}